1. |
Autophagy machinery plays an essential role in traumatic brain injury-induced apoptosis and its related behavioral abnormalities in mice: focus on Sacra gum resin.
Interdonato L, Marino Y, Impellizzeri D, D'Amico R, Siracusa R, Fusco R, Cammilleri G, Pantano L, Modafferi S, Abdelhameed AS, Fritsch T, Rashan LJ, Cuzzocrea S, Calabrese V, Cordaro M, Di Paola R
Traumatic brain injury (TBI) is described as a structural damage or physiological disturbance of brain function that occurs after trauma and causes disability or death in people of all ages. New treatment targets for TBI are being explored because current medicines are frequently ineffectual and poorly tolerated. There is increasing evidence that following TBI, there are widespread changes in autophagy-related proteins in both experimental and clinical settings. The current study investigated if Boswellia Sacra Gum Resin (BSR) treatment (500 mg/kg) could modulate post-TBI neuronal autophagy and protein expression, as well as whether BSR could markedly improve functional recovery in a mouse model of TBI. Taken together our results shows for the first time that BSR limits histological alteration, lipid peroxidation, antioxidant, cytokines release and autophagic flux alteration induced by TBI.
Front Physiol. 2023;14():1320960.
PMID: 38250661 [PubMed - as supplied by publisher]
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2. |
Acetyl-11-Keto-β-Boswellic Acid Accelerates the Repair of Spinal Cord Injury in Rats by Resisting Neuronal Pyroptosis with Nrf2.
Wang Y, Xiong Z, Zhang Q, Liu M, Zhang J, Qi X, Jiang X, Yu W
The primary aim of this study is to delve into the potential of Acetyl-11-keto-β-boswellic acid (AKBA) in ameliorating neuronal damage induced by acute spinal cord injury, as well as to unravel the intricate underlying mechanisms. A cohort of 40 Sprague-Dawley rats was meticulously categorized into four groups. Following a seven-day oral administration of AKBA, damaged spinal cord samples were meticulously procured for Nissl staining and electron microscopy to assess neuronal demise. Employing ELISA, immunofluorescence, Western blot (WB), and quantitative polymerase chain reaction (qPCR), the modulatory effects of AKBA within the context of spinal cord injury were comprehensively evaluated. Furthermore, employing an ex vivo extraction of spinal cord neurons, an ATP + LPS-induced pyroptotic injury model was established. The model was subsequently subjected to Nrf2 inhibition, followed by a battery of assessments involving ELISA, DCFH-DA staining, flow cytometry, immunofluorescence, and WB to decipher the effects of AKBA on the spinal cord neuron pyroptosis model. By engaging the Nrf2-ROS-NLRP3 pathway, AKBA exerted a repressive influence on the expression of the pyroptotic initiator protein Caspase-1, thereby mitigating the release of GSDMD and alleviating pyroptosis. Additionally, AKBA demonstrated the ability to attenuate the release of IL-18 and IL-1β, curbing neuronal loss and expediting the restorative processes within the context of spinal cord injury. Our study elucidates that AKBA can reduce spinal cord neuronal apoptosis, providing a basis for the development of AKBA as a clinical treatment for spinal cord injury.
Int J Mol Sci. 2023 Dec;25(1):.
PMID: 38203528 [PubMed - indexed for MEDLINE]
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3. |
Neuroprotective effects of a combination of Boswellia papyrifera and Syzygium aromaticum on AlCl3 induced Alzheimer's disease in male albino rat.
Aljarari RM
Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by hippocampal, and cortical neuron deterioration, oxidative stress, and severe cognitive dysfunction. Aluminum is a neurotoxin inducer for cognitive impairments associated with AD. The treatment approaches for AD are unsatisfactory. Boswellia papyrifera and Syzygium aromaticum are known for their pharmacological assets, including antioxidant activity. Therefore, the current study explored the possible mitigating effects of a combination of Boswellia papyrifera and Syzygium aromaticum against aluminum chloride (AlCl3) induced AD. The AD model was established using AlCl3 (100 mg/kg), and the rats were orally administrated with Boswellia papyrifera or Syzygium aromaticum or a combination of them daily for 8 weeks. The Y-maze test was used to test cognition in the rats, while acetylcholinesterase (AChE) and oxidative stress markers were estimated in homogenates of the cerebral cortex and hippocampus. Also, the histopathological examination of the cortex and hippocampus were investigated. The results revealed that administration of either B. papyrifera or S. aromaticum extracts significantly improved the cognitive functions of AD rats, enhanced AChE levels, increased oxidative enzymes levels, including SOD and GSH, and reduced MDA levels in homogenates of the cerebral cortex and hippocampus and confirmed by improvement in histological examination. However, using a combination therapy gave better results compared to a single treatment. In conclusion, the present study provided primary evidence for using a combination of B. papyrifera and S. aromaticum to treat cognitive dysfunction associated with AlCl3 Induced AD by improving the AChE levels and modulating oxidative stress in the brain.
Braz J Biol. 2023;83():e272466.
PMID: 37851769 [PubMed - indexed for MEDLINE]
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4. |
The dual face of microglia (M1/M2) as a potential target in the protective effect of nutraceuticals against neurodegenerative diseases.
Darwish SF, Elbadry AMM, Elbokhomy AS, Salama GA, Salama RM
The pathophysiology of different neurodegenerative illnesses is significantly influenced by the polarization regulation of microglia and macrophages. Traditional classifications of macrophage phenotypes include the pro-inflammatory M1 and the anti-inflammatory M2 phenotypes. Numerous studies demonstrated dynamic non-coding RNA modifications, which are catalyzed by microglia-induced neuroinflammation. Different nutraceuticals focus on the polarization of M1/M2 phenotypes of microglia and macrophages, offering a potent defense against neurodegeneration. Caeminaxin A, curcumin, aromatic-turmerone, myricetin, aurantiamide, 3,6'-disinapoylsucrose, and resveratrol reduced M1 microglial inflammatory markers while increased M2 indicators in Alzheimer's disease. Amyloid beta-induced microglial M1 activation was suppressed by andrographolide, sulforaphane, triptolide, xanthoceraside, piperlongumine, and novel plant extracts which also prevented microglia-mediated necroptosis and apoptosis. Asarone, galangin, baicalein, and -mangostin reduced oxidative stress and pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha in M1-activated microglia in Parkinson's disease. Additionally, myrcene, icariin, and tenuigenin prevented the nod-like receptor family pyrin domain-containing 3 inflammasome and microglial neurotoxicity, while -cyperone, citronellol, nobiletin, and taurine prevented NADPH oxidase 2 and nuclear factor kappa B activation. Furthermore, other nutraceuticals like plantamajoside, swertiamarin, urolithin A, kurarinone, Daphne genkwa flower, and extracts showed promising neuroprotection in treating Parkinson's disease. In Huntington's disease, elderberry, curcumin, iresine celosia, , gintonin, and pomiferin showed promising results against microglial activation and improved patient symptoms. Meanwhile, linolenic acid, resveratrol, , icariin, and baicalein protected against activated macrophages and microglia in experimental autoimmune encephalomyelitis and multiple sclerosis. Additionally, emodin, esters of gallic and rosmarinic acids, Agathisflavone, and sinomenine offered promising multiple sclerosis treatments. This review highlights the therapeutic potential of using nutraceuticals to treat neurodegenerative diseases involving microglial-related pathways.
Front Aging. 2023;4():1231706.
PMID: 37744008 [PubMed - as supplied by publisher]
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5. |
Synergistic effects of Boswellia serrata and Acmella oleracea extract combination for treating neuropathic pain in a preclinical model of spared nerve injury.
Boccella S, Mattia C, Perrone M, Morace AM, Karabacak E, Guida F, Maione S, Luongo L
Phytother Res. 2024 Apr;38(4):1731-1734.
PMID: 37661796 [PubMed - indexed for MEDLINE]
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6. |
Acetyl-11-keto-beta boswellic acid(AKBA) modulates CSTC-pathway by activating SIRT-1/Nrf2-HO-1 signalling in experimental rat model of obsessive-compulsive disorder: Evidenced by CSF, blood plasma and histopathological alterations.
Sethi P, Mehan S, Khan Z, Chhabra S
Obsessive-Compulsive disorder (OCD) is a long-term and persistent mental illness characterised by obsessive thoughts and compulsive behaviours. Numerous factors can contribute to the development or progression of OCD. These factors may result from the dysregulation of multiple intrinsic cellular pathways, including SIRT-1, Nrf2, and HO-1. Inhibitors of selective serotonin reuptake (SSRIs) are effective first-line treatments for OCD. In our ongoing research, we have investigated the role of SIRT-1, Nrf2, and HO-1, as well as the neuroprotective potential of Acetyl-11-keto-beta boswellic acid (AKBA) against behavioural and neurochemical changes in rodents treated with 8-OH-DPAT. In addition, the effects of AKBA were compared to those of fluvoxamine (FLX), a standard OCD medication. Injections of 8-OH-DPAT into the intra-dorso raphe nuclei (IDRN) of rats for seven days induced repetitive and compulsive behaviour accompanied by elevated oxidative stress, inflammatory processes, apoptosis, and neurotransmitter imbalances in CSF, blood plasma, and brain samples. Chronic administration of AKBA at 50 mg/kg and 100 mg/kg p.o. restored histopathological alterations in the cortico-striatal-thalamo-cortical (CSTC) pathway, including the cerebral cortex, striatum, and hippocampal regions. Our investigation revealed that when AKBA and fluvoxamine were administered together, the alterations were restored to a greater degree than when administered separately. These findings demonstrate that the neuroprotective effect of AKBA can serve as an effective basis for developing a novel OCD treatment.
Neurotoxicology. 2023 Sep;98():61-85.
PMID: 37549874 [PubMed - indexed for MEDLINE]
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7. |
Acetyl-11-Keto-Beta-Boswellic Acid Activates the Nrf2/HO-1 Signaling Pathway in Schwann Cells to Reduce Oxidative Stress and Promote Sciatic Nerve Injury Repair.
Zhou C, Wang Y, Zhang Q, Zhou G, Ma X, Jiang X, Yu W
Boswellia is a traditional medicine for bruises and injuries. Its main active ingredient, acetyl-11-keto-beta-boswellic acid, has antioxidant and antiapoptotic effects. In this experiment, we used Sprague-Dawley rats to make a sciatic nerve injury model to detect the transcription factor NF-E2-related factor 2/heme oxygenase 1 signaling pathway and apoptosis, combined with clinical indicators, for testing whether acetyl-11-keto-beta-boswellic acid can reduce oxidative stress and promote sciatic nerve repair. Our results showed that acetyl-11-keto-beta-boswellic acid administration promoted myelin regeneration and functional recovery in the rat sciatic nerve, reduced lipid peroxidation levels, upregulated the expression of various antioxidant enzymes and enhanced enzyme activity, decreased the expression levels of apoptosis-related proteins, and promoted nuclear translocation of the transcription factor NF-E2-related factor 2 protein. studies revealed that acetyl-11-keto-beta-boswellic acid reduced HO-induced reactive oxygen species production, restored mitochondrial membrane potential, upregulated the expression of various antioxidant enzymes, and downregulated apoptosis-related indicators in Schwann cells, and these therapeutic effects of acetyl-11-keto-beta-boswellic acid were reversed after ML385 treatment in Schwann cells. In summary, acetyl-11-keto-beta-boswellic acid alleviates oxidative stress and apoptosis caused by sciatic nerve injury in rats by activating the transcription factor NF-E2-related factor 2/heme oxygenase 1 signaling pathway, promotes the recovery of sciatic nerve function in rats, and is a promising therapeutic agent to promote sciatic nerve repair by alleviating excessive oxidative stress.
Planta Med. 2023 Dec;89(15):1468-1482.
PMID: 37541437 [PubMed - indexed for MEDLINE]
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8. |
Modulation of Kv7 Channel Currents by Echinocystic Acid.
Geng D, Li Y, Zheng R, Wang R, Yang B, Zhang H, Zhang Y, Zhang F
Modulation of KCNQ-encoded voltage-gated potassium Kv7/M channel function represents an attractive strategy to treat neuronal excitability disorders such as epilepsy, pain, and depression. The Kv7 channel group includes five subfamily members (Kv7.1-Kv7.5). Pentacyclic triterpenes display extensive pharmacological activities including antitumor, anti-inflammatory, and antidepression effects. In this study, we investigated the effects of pentacyclic triterpenes on Kv7 channels. Our results show that echinocystic acid, ursonic acid, oleanonic acid, demethylzeylasteral, corosolic acid, betulinaldehyde, acetylursolic acid, and -boswellic acid gradually exert decreasing degrees of Kv7.2/Kv7.3 channel current inhibition. Echinocystic acid was the most potent inhibitor, with a half-maximal inhibitory concentration (IC) of 2.5 M. It significantly shifted the voltage-dependent activation curve in a positive direction and slowed the time constant of activation for Kv7.2/Kv7.3 channel currents. Furthermore, echinocystic acid nonselectively inhibited Kv7.1-Kv7.5 channels. Taken together, our findings indicate that echinocystic acid is a novel and potent inhibitor that could be used as a tool to further understand the pharmacological functions of neuronal Kv7 channels. SIGNIFICANCE STATEMENT: Pentacyclic triterpenes reportedly have multiple potential therapeutic uses such as anticancer, anti-inflammatory, antioxidant, and antidepression effects. In the present study, we show that echinocystic acid, ursonic acid, oleanonic acid, and demethylzeylasteral inhibit Kv7.2/Kv7.3 channels to varying degrees. Of these, echinocystic acid was the most potent Kv7.2/Kv7.3 current inhibitor and inhibited Kv7.1-Kv7.5 currents in a nonselective manner.
Mol Pharmacol. 2023 Aug;104(2):42-50.
PMID: 37280100 [PubMed - indexed for MEDLINE]
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9. |
Novel synergistic mechanism of 11-keto-β-boswellic acid and Z-Guggulsterone on ischemic stroke revealed by single-cell transcriptomics.
Liu T, Bai M, Liu M, Li T, Liao Y, Zhao C, Yao M, Wang J, Wen A, Ding Y
Although strides have been made, the challenge of preventing and treating ischemic stroke continues to persist globally. For thousands of years, the natural substances Frankincense and Myrrh have been employed in Chinese and Indian medicine to address cerebrovascular diseases, with the key components of 11-keto-β-boswellic acid (KBA) and Z-Guggulsterone (Z-GS) being the active agents. In this study, the synergistic effect and underlying mechanism of KBA and Z-GS on ischemic stroke were examined using single-cell transcriptomics. Fourteen cell types were identified in KBA-Z-GS-treated ischemic penumbra, and microglia and astrocytes account for the largest proportion. They were further re-clustered into six and seven subtypes, respectively. GSVA analysis reflected the distinct roles of each subtype. Pseudo-time trajectory indicated that Slc1a2 and Timp1 were core fate transition genes regulated by KBA-Z-GS. In addition, KBA-Z-GS synergistically regulated inflammatory reactions in microglia and cellular metabolism and ferroptosis in astrocytes. Most notably, we established an innovative drug-gene synergistic regulation pattern, and genes regulated by KBA-Z-GS were divided into four categories based on this pattern. Finally, Spp1 was demonstrated as the hub target of KBA-Z-GS. Taken together, this study reveals the synergistic mechanism of KBA and Z-GS on cerebral ischemia, and Spp1 may be the synergistic target for that. Precise drug development targeting Spp1 may offer a potential therapeutic approach for treating ischemic stroke.
Pharmacol Res. 2023 Jul;193():106803.
PMID: 37230158 [PubMed - indexed for MEDLINE]
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10. |
Molecular Targets Underlying the Neuroprotective Effects of Boswellic Acid: A Systematic Review.
Khaafi F, Javadi B
BACKGROUND: Neurodegenerative procedures include a large spectrum of disorders with diverse pathological features and clinical manifestations, such as Alzheimer's Disease (AD), Parkinson's disease (PD), Multiple sclerosis, and Amyotrophic lateral sclerosis (ALS). Neurodegenerative diseases (NDs) are indicated by progressive loss of neurons and cognitive function, which is associated with free radical formation, extra and intercellular accumulation of misfolded proteins, oxidative stress, mitochondrial and neurotrophins dysfunction, bioenergetic impairment, inflammation, and apoptotic cell death. Boswellic acid is a pentacyclic triterpene molecule of plant origin that has been applied for treating several inflammatory disorders. Numerous studies have also investigated its' therapeutic potential against multiple NDs.
OBJECTIVE: In this article, we aim to review the neuroprotective effects of boswellic acid on NDs and the related mechanisms of action.
METHODS: The databases of PubMed, Google Scholar, Web of Sciences, and Scopus were searched to find studies that reported the effects of boswellic acid on NDs without time limits. Review articles, letters, editorials, unpublished data, and articles not published in the English language were not included in the study.
RESULTS: Overall, 17 studies were included in the present study (8 NDs in general, 5 AD, 3 PD, and 1 ALS). According to the reports, boswellic acid exerts anti-inflammatory, antioxidant, antiapoptotic, and neuromodulatory effects against NDs. Boswellic acid decreases Tau phosphorylation and amyloid-β (Aβ) generation in AD. This substance also protects nigrostriatal dopaminergic neurons and improves motor impairments in PD and modulates neurotransmitters, decreases the demyelination region, and improves behavioral functions in ALS.
CONCLUSION: Due to the significant effects of boswellic acid in NDs, more clinical studies are necessary to evaluate the pharmacokinetics of this substance because it seems that boswellic acid can be used as a complementary or alternative treatment in patients with NDs.
Mini Rev Med Chem. 2023;23(19):1912-1925.
PMID: 36998129 [PubMed - indexed for MEDLINE]
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11. |
Protective Mechanisms of 3-Acetyl-11-keto-β-Boswellic Acid and Piperine in Fluid Percussion Rat Model of Traumatic Brain Injury Targeting Nrf2 and NFkB Signaling.
Kundu S, Singh S
The current study aimed to investigate the neuroprotective effect of 3-acetyl-11-keto-β-boswellic acid (AKBA) in combination with bioenhancer piperine in lateral fluid percussion injury-induced TBI in experimental rats. Fluid percussion injury was introduced in the rat brain by delivering 50 mmHg of pressure for 3 min to the exposed brain. AKBA 25 mg/kg, 50 mg/kg orally, and AKBA (25 mg/kg, p.o.) in combination with piperine (2.5 mg/kg, p.o.) were administered from day 1 to day 14 to the assigned groups. On the 1st, 7th, and 14th day, behavioral parameters were checked. On the 15th day, animals were euthanized. In TBI rat model, AKBA-piperine combination significantly restored the altered performance of grip strength, rotarod test, open field task, narrow beam task (beam crossing time and no. of foot slips), and Morris water maze (escape latency and time spent in target quadrant) (p < 0.001 vs TBI control). Furthermore, the AKBA-piperine combination significantly reduced pro-inflammatory cytokine level in TBI rat model (p < 0.001 vs TBI control). The combined effect of AKBA and piperine significantly restored oxidative stress parameters level, catecholamines level, and neurotransmitters level (p < 0.001 vs TBI control). Further findings showed that the AKBA-piperine combination prevented histopathological changes (p < 0.001), and the immunohistological study confirmed increased Nrf2-positive cells (p < 0.001 vs TBI control) and reduced nuclear factor kappa B (NFkB) expression (p < 0.001 vs TBI control, p < 0.01 vs TBI + AKBA 50 mg/kg) in the cortical region following AKBA-piperine administration. The present study concluded that AKBA along with piperine achieved anti-oxidant, and anti-inflammatory effects, and also prevented neuronal injury via targeting Nrf2 and NFkB expressions.
Neurotox Res. 2023 Feb;41(1):57-84.
PMID: 36576717 [PubMed - indexed for MEDLINE]
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12. |
AKBA Promotes Axonal Regeneration via RhoA/Rictor to Repair Damaged Sciatic Nerve.
Wang Y, Xiong Z, Zhou C, Zhang Q, Liu S, Dong S, Jiang X, Yu W
The existing studies by our team demonstrated the pro-recovery effect of 3-Acetyl-11-keto-beta-boswellic acid (AKBA) on a sciatic nerve injury. To further investigate the role of AKBA in peripheral nerve injury repair, The TMT quantitative proteomics technique was used to obtain differentially significant proteins in a Sham group, Model group, and AKBA group. After that, three time points (5, 14, and 28 d) and four groups (Sham + AKBA, Sham, Model, and AKBA) were set up, and immunoblotting, immunofluorescence, and cellular assays were applied to investigate the expression of CDC42, Rac1, RhoA, and Rictor in the sciatic nerve at different time points for each group in more depth. The results showed that AKBA enriched the cellular components of the myelin sheath and axon regeneration after a sciatic nerve injury and that AKBA upregulated CDC42 and Rac1 and downregulated RhoA expression 5 d after a sciatic nerve injury, promoting axon regeneration and improving the repair of a sciatic nerve injury in rats. Rictor is regulated by AKBA and upregulated in PC12 cells after AKBA action. Our findings provide a new basis for AKBA treatment of a peripheral nerve injury.
Int J Mol Sci. 2022 Dec;23(24):.
PMID: 36555556 [PubMed - indexed for MEDLINE]
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13. |
Synthesis and antidepressant-like effects of new 5-epi-incensole and 5-epi- incensole acetate in chronic unpredictable mild stress model of depression; behavioural and biochemical correlates.
Avula SK, Khan A, Halim SA, Rehman NU, Karim N, Khan I, Csuk R, Das B, Al-Harrasi A
In the current investigation, 5-epi-incensole (3) and 5-epi-incensole acetate (5) were synthesized from the most potent anti-depressant constituents incensole (1) and incensole acetate (2) of Boswellia papyrifera Hochst. The resulting compounds were evaluated for their ability to ameliorate depressive symptoms in forced swim test (FST) and tail suspension test (TST) in chronic unpredictable mild stress (CUMS) induced depression paradigm. The results demonstrated that compounds 3 and 5 at the doses of 1 and 3 mg/kg administered for 28 days, significantly reduced the immobility time in FST and TST and were devoid of any effect on locomotor activity in the open field test (OFT). Both compounds 3 and 5 also reversed CUMS-induced reduction in the weight of animals and aversion in sucrose preference. The tested compounds also inhibited Monoamine oxidase-A (MAO) enzyme and increased the levels of brain noradrenaline (NA) and 5-Hydroxytryptamine (5-HT), decreased plasma corticosterone and pro-inflammatory cytokines including TNF-α, IL-6 in hippocampal homogenates. Compounds 3 and 5 also significantly reduced the increased lipid peroxidation and nitrite levels; decreased glutathione levels, and catalase activities in mice undergoing CUMS protocol. The binding mode of compounds 3 and 5 was predicted at the monoamine oxidase substrate binding site by molecular docking having docking scores of > -6 kcal/mol. Taken together these data revealed that compounds 3 and 5 exerted antidepressant-like effects in chronic unpredictable mild stress-induced depression paradigm and are likely mediated via modulating the central oxidative stress, MAO-A activity with a consequent increase in brain NA and 5-HT levels in inflammatory pathways.
Biomed Pharmacother. 2022 Dec;156():113960.
PMID: 36411640 [PubMed - indexed for MEDLINE]
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14. |
Boswellic acids as promising agents for the management of brain diseases.
Rajabian A, Farzanehfar M, Hosseini H, Arab FL, Nikkhah A
Boswellic acid (BA)s are pentacyclic triterpenic acids present in gum resin of Boswellia species (such as B. serrata and B. carterii). They possess a variety of pharmacological effects such as anti-inflammatory, anti-oxidant, and anti-excitotoxic effects. These properties may have potential therapeutic implication in neurological disorders. Notably, the BAs-induced neuroprotection is proposed to be associated with the ability to reduce neurotoxic aggregates, decrease oxidative stress, and improve cognitive dysfunction. Recently, BAs have been suggested as potential agents for the treatment of brain tumors due to their potential to attenuate cell proliferation, migration, metastasis, angiogenesis, and promote apoptosis during both in vitro and in vivo studies. The present review aims to address these studies and highlights the possible underlying mechanisms of the observed effects. Besides, novel formulations and improving pharmacokinetic properties may enhance the therapeutic efficacy of BAs.
Life Sci. 2023 Jan;312():121196.
PMID: 36400202 [PubMed - indexed for MEDLINE]
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15. |
Frankincense-Myrrh treatment alleviates neuropathic pain via the inhibition of neuroglia activation mediated by the TLR4/MyD88 pathway and TRPV1 signaling.
Liao Y, Guo C, Wen A, Bai M, Ran Z, Hu J, Wang J, Yang J, Ding Y
BACKGROUND: Neuroglia are important modulators of neuronal functionality, and thus play an integral role in the pathogenesis and treatment of neuropathic pain (NP). According to traditional Chinese medicine, Frankincense-Myrrh is capable of "activating blood and dissipating blood stasis", and as such these two biological compounds are commonly used to treat NP, however, the mechanisms underlying the efficacy of such treatment are unclear.
PURPOSE: This study aimed to further elucidate the protective effects associated with the Frankincense-Myrrh treatment of NP.
METHODS: A chronic sciatic nerve compression injury (CCI) model of NP was established, after which animals were gavaged with Frankincense, Myrrh, Frankincense-Myrrh, or the positive control drug pregabalin for 14 days. Network pharmacology approaches were used to identify putative pathways and targets associated with the Frankincense-Myrrh-mediated treatment of NP, after which these targets were subjected to in-depth analyses. The impact of TLR4 blockade on NP pathogenesis was assessed by intrathecally administering a TLR4 antagonist (LRU) or the MyD88 homodimerization inhibitory peptide (MIP).
RESULTS: Significant alleviation of thermal and mechanical hypersensitivity in response to Frankincense and Myrrh treatment was observed in NP model mice, while network pharmacology analyses suggested that the pathogenesis of NP may be related to TLR4/MyD88-mediated neuroinflammation. Consistently, Frankincense-Myrrh treatment was found to reduce TLR4, MyD88, and p-p65 expression in spinal dorsal horn neuroglia from treated animals, in addition to inhibiting neuronal TRPV1 and inflammatory factor expression. Intrathecal LRU and MIP delivery were sufficient to alleviate thermal and mechanical hyperalgesia in these CCI model mice, with concomitant reductions in neuronal TRPV1 expression and neuroglial activation in the spinal dorsal horn.
CONCLUSION: These data suggest that Frankincense-Myrrh treatment was sufficient to alleviate NP in part via inhibiting TLR4/MyD88 pathway and TRPV1 signaling activity. Blocking TLR4 and MyD88 activation may thus hold value as a means of treating NP.
Phytomedicine. 2023 Jan;108():154540.
PMID: 36379093 [PubMed - indexed for MEDLINE]
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16. |
Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington's Disease.
Albekairi TH, Kamra A, Bhardwaj S, Mehan S, Giri A, Suri M, Alshammari A, Alharbi M, Alasmari AF, Narula AS, Kalfin R
Huntington's disease (HD) is distinguished by a triple repeat of CAG in exon 1, an increase in poly Q in the Htt gene, and a loss of GABAergic medium spiny neurons (MSN) in the striatum and white matter of the cortex. Mitochondrial ETC-complex dysfunctions are involved in the pathogenesis of HD, including neuronal energy loss, synaptic neurotrophic decline, neuronal inflammation, apoptosis, and grey and white matter destruction. A previous study has demonstrated that beta Boswellic acid (β-BA), a naturally occurring phytochemical, has several neuroprotective properties that can reduce pathogenic factors associated with various neurological disorders. The current investigation aimed to investigate the neuroprotective potential of β-BA at oral doses of 5, 10, and 15 mg/kg alone, as well as in conjunction with the potent antioxidant vitamin E (8 mg/kg, orally) in 3-NP-induced experimental HD rats. Adult Wistar rats were separated into seven groups, and 3-NP, at a dose of 10 mg/kg, was orally administered to each group of adult Wistar rats beginning on day 1 and continuing through day 14. The neurotoxin 3-NP induces neurodegenerative, g, neurochemical, and pathological alterations in experimental animals. Continuous injection of 3-NP, according to our results, aggravated HD symptoms by suppressing ETC-complex-II, succinate dehydrogenase activity, and neurochemical alterations. β-BA, when taken with vitamin E, improved behavioural dysfunctions such as neuromuscular and motor impairments, as well as memory and cognitive abnormalities. Pharmacological treatments with β-BA improved and restored ETC complexes enzymes I, II, and V levels in brain homogenates. β-BA treatment also restored neurotransmitter levels in the brain while lowering inflammatory cytokines and oxidative stress biomarkers. β-BA's neuroprotective potential in reducing neuronal death was supported by histopathological findings in the striatum and cortex. As a result, the findings of this research contributed to a better understanding of the potential role of natural phytochemicals β-BA in preventing neurological illnesses such as HD.
Biomedicines. 2022 Nov;10(11):.
PMID: 36359390 [PubMed - as supplied by publisher]
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17. |
Neuropharmacological Effects of Terpenoids on Preclinical Animal Models of Psychiatric Disorders: A Review.
Mony TJ, Elahi F, Choi JW, Park SJ
Terpenoids are widely distributed in nature, especially in the plant kingdom, and exhibit diverse pharmacological activities. In recent years, screening has revealed a wide variety of new terpenoids that are active against different psychiatric disorders. This review synthesized the current published preclinical studies of terpenoid use in psychiatric disorders. This review was extensively investigated to provide empirical evidence regarding the neuropharmacological effects of the vast group of terpenoids in translational models of psychiatric disorders, their relevant mechanisms of action, and treatment regimens with evidence of the safety and psychotropic efficacy. Therefore, we utilized nine (9) electronic databases and performed manual searches of each. The relevant data were retrieved from the articles published until present. We used the search terms "terpenoids" or "terpenes" and "psychiatric disorders" ("psychiatric disorders" OR "psychiatric diseases" OR "neuropsychiatric disorders" OR "psychosis" OR "psychiatric symptoms"). The efficacy of terpenoids or biosynthetic compounds in the terpenoid group was demonstrated in preclinical animal studies. Ginsenosides, bacosides, oleanolic acid, asiatic acid, boswellic acid, mono- and diterpenes, and different forms of saponins and triterpenoids were found to be important bioactive compounds in several preclinical studies of psychosis. Taken together, the findings of the present review indicate that natural terpenoids and their derivatives could achieve remarkable success as an alternative therapeutic option for alleviating the core or associated behavioral features of psychiatric disorders.
Antioxidants (Basel). 2022 Sep;11(9):.
PMID: 36139909 [PubMed - as supplied by publisher]
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18. |
Inhibition Of Tau Protein Aggregation By a Chaperone-like β-Boswellic Acid Conjugated To Gold Nanoparticles.
Gharb M, Nouralishahi A, Riazi A, Riazi G
A potential therapeutic strategy to inhibit tau protein aggregation in neurons has substantial effects on preventing or controlling Alzheimer's disease (AD). In this work, we designed a covalent and noncovalent conjugation of β-boswellic acid (BA) to gold nanoparticles (GNPs). We provided the opportunity to investigate the effect of the surface composition of BA-GNPs on the aggregation of the tau protein 1N/4R isoform in vitro. HR-TEM and FESEM micrographs revealed that GNPs were spherical and uniform, smaller than 25 nm. According to UV-visible and FTIR data, BA was successfully conjugated to GNPs. The finding illustrates the effect of the surface charge, size, and hydrophobicity of BA-GNPs on the kinetics of tau protein aggregation. The size and surface area of U-G-BA demonstrated that inhibited tau aggregation more effectively than covalently linked BA. The proposed method for preventing tau aggregation was monomer reduction. At the same time, a chaperone-like feature of GNP-BA while sustaining a tau native structure prevented the additional formation of fibrils. Overall, this study provides insight into the interaction of GNP-BAs with a monomer of tau protein and may suggest novel future therapies for AD.
ACS Omega. 2022 Aug;7(34):30347-30358.
PMID: 36061732 [PubMed - as supplied by publisher]
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19. |
Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis.
Upadhayay S, Mehan S, Prajapati A, Sethi P, Suri M, Zawawi A, Almashjary MN, Tabrez S
Multiple sclerosis (MS) is a severe immune-mediated neurological disease characterized by neuroinflammation, demyelination, and axonal degeneration in the central nervous system (CNS). This is frequently linked to motor abnormalities and cognitive impairments. The pathophysiological hallmarks of MS include inflammatory demyelination, axonal injury, white matter degeneration, and the development of CNS lesions that result in severe neuronal degeneration. Several studies suggested downregulation of nuclear factor erythroid-2-related factor-2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling is a causative factor for MS pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active obtained from , possessing antioxidant and anti-inflammatory properties. The present study explores the protective potential of AKBA on behavioral, molecular, neurochemical, and gross pathological abnormalitiesandhistopathological alterations by H&E and LFB staining techniques in an experimental model of multiple sclerosis, emphasizing the increase inNrf2/HO-1 levels in the brain. Moreover, we also examine the effect of AKBA on the intensity of myelin basic protein (MBP) in CSF and rat brain homogenate. Specific apoptotic markers (Bcl-2, Bax, andcaspase-3) were also estimated in rat brain homogenate. Neuro behavioralabnormalities in rats were examined using an actophotometer, rotarod test, beam crossing task (BCT),and Morris water maze (MWM). AKBA 50 mg/kg and 100 mg/kg were given orally from day 8 to 35 to alleviate MS symptoms in the EB-injected rats. Furthermore, cellular, molecular, neurotransmitter, neuroinflammatory cytokine, and oxidative stress markers in rat whole brain homogenate, blood plasma, and cerebral spinal fluid were investigated. This study shows that AKBA upregulates the level of antioxidant proteins such as Nrf2 and HO-1 in the rat brain. AKBA restores altered neurochemical levels, potentially preventing gross pathological abnormalities during MS progression.
Genes (Basel). 2022 Jul;13(8):.
PMID: 35893061 [PubMed - indexed for MEDLINE]
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20. |
Methanolic Extract of Boswellia serrata Gum Protects the Nigral Dopaminergic Neurons from Rotenone-Induced Neurotoxicity.
Shadfar S, Khanal S, Bohara G, Kim G, Sadigh-Eteghad S, Ghavami S, Choi H, Choi DY
Boswellia serrata gum is a natural product that showed beneficial effects on neurodegenerative diseases in recent studies. In this study, we investigated the effects of Boswellia serrata resin on rotenone-induced dopaminergic neurotoxicity. Firstly, we attempted to see if the resin can induce AMP-activated protein kinase (AMPK) signaling pathway which has been known to have broad neuroprotective effects. Boswellia increased AMPK phosphorylation and reduced phosphorylation of mammalian target of rapamycin (p-mTOR) and α-synuclein (p-α-synuclein) in the striatum while increased the expression level of Beclin1, a marker for autophagy and brain-derived neurotrophic factor. Next, we examined the neuroprotective effects of the Boswellia extract in the rotenone-injected mice. The results showed that Boswellia evidently attenuated the loss of the nigrostriatal dopaminergic neurons and microglial activation caused by rotenone. Moreover, Boswellia ameliorated rotenone-induced decrease in the striatal dopamine and impairment in motor function. Accumulation of α-synuclein meditated by rotenone was significantly ameliorated by Boswellia. Also, we showed that β-boswellic acid, the active constituents of Boswellia serrata gum, induced AMPK phosphorylation and attenuated α-synuclein phosphorylation in SHSY5 cells. These results suggest that Boswellia protected the dopaminergic neurons from rotenone neurotoxicity via activation of the AMPK pathway which might be associated with attenuation of α-synuclein aggregation and neuroinflammation. Further investigations are warranted to identify specific molecules in Boswellia which are responsible for the neuroprotection.
Mol Neurobiol. 2022 Sep;59(9):5874-5890.
PMID: 35804280 [PubMed - indexed for MEDLINE]
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21. |
Author Correction: Neuroprotection by acetyl-11-keto-β-boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway.
Ding Y, Chen M, Wang M, Wang M, Zhang T, Park J, Zhu Y, Guo C, Jia Y, Li Y, Wen A
Sci Rep. 2022 Jul;12(1):11547.
PMID: 35798757 [PubMed - as supplied by publisher]
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22. |
Incensole derivatives from frankincense: Isolation, enhancement, synthetic modification, and a plausible mechanism of their anti-depression activity.
Ur Rehman N, Al-Shidhani S, Karim N, Khan A, Khan I, Ahsan Halim S, Khan Sadozai S, Kumar Avula S, Csuk R, Al-Harrasi A
Encouraged by the potent anti-depression activities of incensole (1) and incensole acetate (2) isolated from the resin of Boswellia papyrifera in our previous work, different derivatives of 1 and 2 were synthesized in the present study. The reaction of 1 with m-CPBA afforded the mono-epoxide derivative 3a, while the same reaction with 2 led to three different epoxide derivatives 3a, 3b, and 3c. Oxidation of 1 with PCC to get compound 3b, however along with the target 3b, the reaction gave three interesting side products (3c-3e). Oxime (3b-1) resulted from the reaction of 3b with hydroxylamine hydrochloride in pyridine, while epoxidation of 2 generate three epoxide products (4a-4c). The structures of all products were unambiguously confirmed using NMR and Mass spectrometry. Compounds 3a-e and 4a-c (0.1-3 mg/kg, i.p.) demonstrated promising anti-depression activities in classical mouse models of depression of FST and TST. The results showed that compounds 3a-e and 4a-c (0.1-3 mg/kg, i.p.) caused dose dependent reduction in immobility time compared to the vehicle control, with 3c-3e and 4b-4c demonstrating higher potency and efficacy. The findings of the open field test excluded the motor effects of these compounds, thus further confirming their anti-depression activity. Preliminary investigation into their mechanism of action using GABA antagonist, PTZ and molecular docking has predicted that compounds 3e and 4c bind at the GABA binding site of GABA receptor to produce GABAergic effects. Furthermore, the promising anti-depression potency of compounds 1 and 2 and their derivatives make them lead compounds for drug discovery.
Bioorg Chem. 2022 Sep;126():105900.
PMID: 35671644 [PubMed - indexed for MEDLINE]
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23. |
Boswellic acids ameliorate neurodegeneration induced by AlCl: the implication of Wnt/β-catenin pathway.
Mohamed EA, Ahmed HI, Zaky HS, Badr AM
Alzheimer's disease (AD) is a neurodegenerative disease (ND) that represents the principal cause of dementia. Effective treatment is still lacking. Without prevention, Alzheimer's disease (AD) incidence is expected to triple within 30 years. The risk increases in highly polluted areas and is positively linked to chronic aluminum (Al) exposure. Canonical Wingless-Int (Wnt)/β-catenin pathway has been found to play a considerable role in ND pathogenesis. Resins of Boswellia serrata (frankincense) have been used traditionally for their psychoactive activity, in addition to their memory-boosting effects. Boswellic acids (BA) are pentacyclic triterpenes. They have antioxidant, anti-inflammatory, antinociceptive, and immunomodulatory activities. This study aimed to elucidate the role of the Wnt/β-catenin pathway in BA protective activity against aluminum-induced Alzheimer's disease. For 6 weeks, rats were treated daily with AlCl3 (100 mg/kg/i.p.) either alone or with BA (125 or 250 mg/kg PO). Results indicated that BA significantly improved learning and memory impairments induced by AlCl treatment. Moreover, BA treatment significantly decreased acetylcholinesterase levels and reduced amyloid-beta (Aβ) expression. In addition, BA ameliorated the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), inhibited lipid peroxidation, and increased total antioxidants in the brain. Indeed, BA significantly suppressed AlCl-induced decrease of brain-derived neurotrophic factor, pGSK-3β (Ser 9), and β-catenin. BA (250 mg/kg) showed a significant protective effect compared to a lower dose. The results conclude that BA administration modulated the expression of Wnt/β-catenin pathway-related parameters, contributing to BA's role against Al-induced Alzheimer's disease. Effect of Boswellic acids on AlCl-induced neurodegenerative changes. ChE cholinesterase, Ach acetylcholine, BDNF brain-derived neurotrophic factor, IL-1β interleukin-1β, TNF-α tumor necrosis factor-α.
Environ Sci Pollut Res Int. 2022 Oct;29(50):76135-76143.
PMID: 35668264 [PubMed - indexed for MEDLINE]
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24. |
Acetyl-11-keto-beta-boswellic acid promotes sciatic nerve repair after injury: molecular mechanism.
Wang Y, Xiong ZL, Ma XL, Zhou C, Huo MH, Jiang XW, Yu WH
Previous studies showed that acetyl-11-keto-beta-boswellic acid (AKBA), the active ingredient in the natural Chinese medicine Boswellia, can stimulate sciatic nerve injury repair via promoting Schwann cell proliferation. However, the underlying molecular mechanism remains poorly understood. In this study, we performed genomic sequencing in a rat model of sciatic nerve crush injury after gastric AKBA administration for 30 days. We found that the phagosome pathway was related to AKBA treatment, and brain-derived neurotrophic factor expression in the neurotrophic factor signaling pathway was also highly up-regulated. We further investigated gene and protein expression changes in the phagosome pathway and neurotrophic factor signaling pathway. Myeloperoxidase expression in the phagosome pathway was markedly decreased, and brain-derived neurotrophic factor, nerve growth factor, and nerve growth factor receptor expression levels in the neurotrophic factor signaling pathway were greatly increased. Additionally, expression levels of the inflammatory factors CD68, interleukin-1β, pro-interleukin-1β, and tumor necrosis factor-α were also decreased. Myelin basic protein- and β3-tubulin-positive expression as well as the axon diameter-to-total nerve diameter ratio in the injured sciatic nerve were also increased. These findings suggest that, at the molecular level, AKBA can increase neurotrophic factor expression through inhibiting myeloperoxidase expression and reducing inflammatory reactions, which could promote myelin sheath and axon regeneration in the injured sciatic nerve.
Neural Regen Res. 2022 Dec;17(12):2778-2784.
PMID: 35662229 [PubMed - as supplied by publisher]
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25. |
Beta-Boswellic Acid Protects Against Cerebral Ischemia/Reperfusion Injury via the Protein Kinase C Epsilon/Nuclear Factor Erythroid 2-like 2/Heme Oxygenase-1 Pathway.
Wang M, Yu J, Yang Q, Guo C, Zhang W, Li W, Weng Y, Ding Y, Wang J
Ischemic strokes are associated with a high rate of disability and death globally. Cerebral ischemia/reperfusion (I/R) injury is a type of brain damage associated with oxidative stress after an ischemic stroke. Beta-boswellic acid (β-BA) reportedly exerts antioxidant and neuroprotective effects, but its role in cerebral I/R injury is unclear. The aim of this research was to investigate the neuroprotective effects, as well as the mechanisms of β-BA in cerebral I/R injury. In vivo experiments were conducted using a rat middle cerebral artery occlusion and reperfusion (MCAO/R) model, and in vitro experiments were performed using a rat neuronal oxygen-glucose deprivation and reoxygenation (OGD/R) model. Triphenyltetrazolium chloride staining, neurological function scores, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling, hematoxylin and eosin staining, and antioxidant levels in the brain were used to assess the effects of β-BA. Flow cytometry was used to detect reactive oxygen species and apoptotic cells. Western blotting and immunofluorescence staining were used to measure protein levels. The results showed that β-BA markedly improved neurological deficits and decreased infarct volume and necrotic neurons in rats. The in vitro results showed that β-BA protected neurons against OGD/R-induced injury. Additionally, β-BA significantly increased the phosphorylation of protein kinase C epsilon (PRKCE) at S729, the translocation of nuclear factor erythroid 2-like 2 (NFE2L2), and expression of heme oxygenase-1 (HMOX1). This study demonstrates that β-BA exerts neuroprotective effects against cerebral I/R via the activation of the PRKCE/NFE2L2/HMOX1 pathway and is a potential therapeutic candidate for ischemic stroke.
Mol Neurobiol. 2022 Jul;59(7):4242-4256.
PMID: 35505050 [PubMed - indexed for MEDLINE]
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26. |
The Biological Activity of 3-O-Acetyl-11-keto-β-Boswellic Acid in Nervous System Diseases.
Gong Y, Jiang X, Yang S, Huang Y, Hong J, Ma Y, Fang X, Fang Y, Wu J
Frankincense is a hard gelatinous resin exuded by Boswellia serrata. It contains a complex array of components, of which acetyl-11-keto-beta-boswellic acid (AKBA), a pentacyclic triterpenoid of the resin class, is the main active component. AKBA has a variety of physiological actions, including anti-infection, anti-tumor, and antioxidant effects. The use of AKBA for the treatment of mental diseases has been documented as early as ancient Greece. Recent studies have found that AKBA has anti-aging and other neurological effects, suggesting its potential for the treatment of neurological diseases. This review focuses on nervous system-related diseases, summarizes the functions and mechanisms of AKBA in promoting nerve repair and regeneration after injury, protecting against ischemic brain injury and aging, inhibiting neuroinflammation, ameliorating memory deficits, and alleviating neurotoxicity, as well as having anti-glioma effects and relieving brain edema. The mechanisms by which AKBA functions in different diseases and the relationships between dosage and biological effects are discussed in depth with the aim of increasing understanding of AKBA and guiding its use for the treatment of nervous system diseases.
Neuromolecular Med. 2022 Dec;24(4):374-384.
PMID: 35303275 [PubMed - indexed for MEDLINE]
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27. |
Molecular evidences on anti-inflammatory, anticancer, and memory-boosting effects of frankincense.
Khajehdehi M, Khalaj-Kondori M, Baradaran B
Chemical diversity of natural products with drug-like features has attracted much attention from medicine to develop more safe and effective drugs. Their anti-inflammatory, antitumor, analgesic, and other therapeutic properties are sometimes more successful than chemical drugs in controlling disease due to fewer drug resistance and side effects and being more tolerable in a long time. Frankincense, the oleo gum resin extracted from the Boswellia species, contains some of these chemicals. The anti-inflammatory effect of its main ingredient, boswellic acid, has been traditionally used to treat many diseases, mainly those target memory functions. In this review, we have accumulated research evidence from the beneficial effect of Frankincense consumption in memory improvement and the prevention of inflammation and cancer. Besides, we have discussed the molecular pathways mediating the therapeutic effects of this natural supplement.
Phytother Res. 2022 Mar;36(3):1194-1215.
PMID: 35142408 [PubMed - indexed for MEDLINE]
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28. |
Review of the Chemical Composition, Pharmacological Effects, Pharmacokinetics, and Quality Control of .
Huang K, Chen Y, Liang K, Xu X, Jiang J, Liu M, Zhou F
OBJECTIVE: This review aimed to systematically summarize studies that investigated the bioactivities of compounds and extracts from Boswellia.
METHODS: A literature review on the pharmacological properties and phytochemicals of was performed. The information was retrieved from secondary databases such as PubMed, Chemical Abstracts Services (SciFinder), Google Scholar, and ScienceDirect.
RESULTS: The various extracts and compounds demonstrated pharmacological properties, such as anti-inflammatory, antitumour, and antioxidant activities. B. exhibited a positive effect on the treatment and prevention of many ageing diseases, such as diabetes, cancer, cardiovascular disease, and neurodegenerative diseases.
CONCLUSION: Here, we highlight the pharmacological properties and phytochemicals of and propose further evidence-based research on plant-derived remedies and compounds.
Evid Based Complement Alternat Med. 2022;2022():6627104.
PMID: 35069765 [PubMed - as supplied by publisher]
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29. |
Mechanistic role of boswellic acids in Alzheimer's disease: Emphasis on anti-inflammatory properties.
Siddiqui A, Shah Z, Jahan RN, Othman I, Kumari Y
The resin/gum of Boswellia species belonging to the family of Burseraceae is a naturally occurring mixture of bioactive compounds, which was traditionally used as a folk medicine to treat conditions like chronic inflammation. Several research studies have also explored its' therapeutic potential against multiple neurodegenerative diseases such as Alzheimer's disease (AD). The main chemical constituents of this gum include boswellic acids (BAs) like 3-O-acetyl-11-keto-β boswellic acid (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD. It is also involved in inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels as well as its binding with nicotinic receptors to produce anti-inflammatory effects. Multiple shreds of evidence have demonstrated that BAs modulate key molecular targets and signalling pathways like 5-lipoxygenase/cyclooxygenase, Nrf2, NF-kB, cholinergic, amyloid-beta (Aβ), and neurofibrillary tangles formation (NFTs) that are involved in AD progression. The present review focuses on the possible mechanistic therapeutic role of BAs in modulating the 5-LOX/COX pathway in arachidonic acid metabolism, activating Nrf2 through binding of ARE, inhibiting NF-kB and AChE activity. In addition, an inhibition of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) induced neurotoxicity and neuroinflammation in AD by BAs is also discussed in this review. We have also highlighted that BAs possess beneficial effects in AD by targeting multiple molecular pathways and makes it an emerging drug candidate for treating neurodegenerative diseases.
Biomed Pharmacother. 2021 Dec;144():112250.
PMID: 34607104 [PubMed - indexed for MEDLINE]
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30. |
3-O-Acetyl-11-keto-β-boswellic acid ameliorates chronic unpredictable mild stress induced HPA axis dysregulation in relation with glutamate/GABA aberration in depressive rats.
Gunasekaran V, Augustine A, Avarachan J, Khayum A, Ramasamy A
Overt expression of brain glucocorticoid receptor (GR) leads to elevation of glutamate release causes cerebral excitotoxicity which in turn produce neuropsychological disorders. The aim of our work is to study the consequence of 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) on chronic unpredictable mild stress (CUMS) induced HPA axis dysregulation in relative to glutamate and GABA irregularity in depressive rats. AKBA (5, 10 &15mg/kg) was administered for 28 days parallel with CUMS induction in rats. Behavioural studies, tail suspension test (TST), open field exploratory (OFT) and forced swim test (FST) were performed. Biochemical studies including plasma corticosterone, glutamate GABA and glutamic acid decarboxylase (GAD) enzyme activity were studied. Glucocorticoid receptor expression and brain histology were studied to observe the effect of AKBA. CUMS induction results in depressive state of the animals were confirmed by the sucrose preference test. The administration of AKBA significantly reduced the immobility time and improved the exploratory behaviour. Plasma corticosterone and brain glutamate level was decreased and GABA level were increased significantly evident with GAD activation in AKBA-treated animals, further confirmed with decreased GR expression improves architecture of prefrontal cortex region. Correlation study illustrates behavioural improvements undeviating the biochemical alteration and GR expression after AKBA treatment during depression. AKBA significantly reversed the CUMS-induced glutamate/GABA abnormalities through the adaptation of central HPA axis regulation. Hence this study concludes that AKBA can be a better alternative to treat depressive disorders.
Clin Exp Pharmacol Physiol. 2021 Dec;48(12):1633-1641.
PMID: 34343356 [PubMed - indexed for MEDLINE]
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31. |
An engineered microfluidic blood-brain barrier model to evaluate the anti-metastatic activity of β-boswellic acid.
Vakilian S, Alam K, Al-Kindi J, Jamshidi-Adegani F, Rehman NU, Tavakoli R, Al-Riyami K, Hasan A, Zadjali F, Csuk R, Al-Harrasi A, Al-Hashmi S
BACKGROUND: The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models.
MAIN METHODS: In this study, the Geltrex-based Transwell and microfluidic BBB models were applied to screen the effect of β-boswellic acid (β-BA) on the metastasis of MDA-MB-231 cells through the BBB in static and dynamic conditions, respectively.
MAJOR RESULTS: The toxicity assay revealed that β-BA deteriorates MDA-MB-231 cells, while β-BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans-endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with β-BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of β-BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. β-BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that β-BA-mediated metastasis inhibition was significantly higher than that mediated by Cis.
CONCLUSIONS AND IMPLICATIONS: In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models.
Biotechnol J. 2021 Oct;16(10):e2100044.
PMID: 34313388 [PubMed - indexed for MEDLINE]
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32. |
Protection of Beta Boswellic Acid against Streptozotocin-induced Alzheimer's Model by Reduction of Tau Phosphorylation Level and Enhancement of Reelin Expression.
Shasaltaneh MD, Naghdi N, Ramezani S, Alizadeh L, Riazi GH
Alzheimer's disease is a growing general health concern with huge implications for individuals and society. Beta boswellic acid, a major compound of the plant, has long been used for the treatment of various inflammatory diseases. The exact mechanism of beta boswellic acid action in Alzheimer's disease pathogenesis remains unclear. In the current study, the protective effect of beta boswellic acid on streptozotocin-induced sporadic Alzheimer's disease was surveyed. Alzheimer's disease model was induced using streptozotocin followed by an assessment of the treatment effects of beta boswellic acid in the presence of streptozotocin. The prevention effect of beta boswellic acid on Alzheimer's disease induction by streptozotocin was evaluated. Behavioral activities in the treated rats were evaluated. Histological analysis was performed. Phosphorylation of tau protein at residues Ser396 and Ser404 and the expression of reelin protein were determined. Glial fibrillary acidic protein immunofluorescence staining was applied in the hippocampus regions. Our findings indicated that beta boswellic acid decreased traveled distance and escape latency in the prevention (beta boswellic acid + streptozotocin) and treatment (streptozotocin + beta boswellic acid) groups compared to control during the acquisition test. It increased "time spent" (%) in the target quadrant. Reelin level was enhanced in rats treated with beta boswellic acid. Tau hyperphosphorylation (p-tau404) and glial fibrillary acidic protein were decreased in the prevention group while the expression of reelin protein in both groups was increased. We could suggest that the anti-inflammatory property of beta boswellic acid is one of the main factors involving in the improvement of learning and memory in rats. Therefore the antineurodegenerative effect of beta boswellic acid may be due to its ability to reactivate reelin protein.
Planta Med. 2022 Apr;88(5):367-379.
PMID: 34116571 [PubMed - indexed for MEDLINE]
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33. |
Nrf2/HO-1 Signaling Activator Acetyl-11-keto-beta Boswellic Acid (AKBA)-Mediated Neuroprotection in Methyl Mercury-Induced Experimental Model of ALS.
Minj E, Upadhayay S, Mehan S
Methylmercury (MeHg) is a potent neurotoxin that causes neurotoxicity and neuronal cell death. MeHg exposure also leads to oligodendrocyte destruction, glial cell overactivation, and demyelination of motor neurons in the motor cortex and spinal cord. As a result, MeHg plays an important role in the progression of amyotrophic lateral sclerosis (ALS)-like neurocomplications. ALS is a fatal neurodegenerative disorder in which neuroinflammation is the leading cause of further CNS demyelination. Nuclear factor erythroid-2-related factor-2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway was thought to be a potential target for neuroprotection in ALS. Acetyl-11-keto-beta-boswellic acid (AKBA) is a multi-component pentacyclic triterpenoid mixture derived from Boswellia serrata with anti-inflammatory and antioxidant properties. The research aimed to investigate whether AKBA, as a Nrf2 / HO-1 activator, can provide protection against ALS. Thus, we explored the role of AKBA on the Nrf2/HO-1 signaling pathway in a MeHg-induced experimental ALS model. In this study, ALS was induced in Wistar rats by oral gavage of MeHg 5 mg/kg for 21 days. An open field test, force swim test, and grip strength were performed to observe experimental rats' motor coordination behaviors. In contrast, a morris water maze was performed for learning and memory. Administration of AKBA 50 mg/kg and AKBA 100 mg/kg continued from day 22 to 42. Neurochemical parameters were evaluated in the rat's brain homogenate. In the meantime, post-treatment with AKBA significantly improved behavioral, neurochemical, and gross pathological characteristics in the brain of rats by increasing the amount of Nrf2/HO-1 in brain tissue. Collectively, our findings indicated that AKBA could potentially avoid demyelination and encourage remyelination.
Neurochem Res. 2021 Nov;46(11):2867-2884.
PMID: 34075522 [PubMed - indexed for MEDLINE]
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34. |
Sublingual AKBA Exerts Antidepressant Effects in the Aβ-Treated Mouse Model.
Morgese MG, Bove M, Francavilla M, Schiavone S, Dimonte S, Colia AL, Bevilacqua M, Trabace L, Tucci P
The 3-O-acetyl-11-keto-β-boswellic acid (AKBA) is the most active compound of proposed for treating neurodegenerative disorders, including Alzheimer's disease (AD), characterized in its early phase by alteration in mood. Accordingly, we have previously demonstrated that an intracerebroventricular injection of soluble amyloid beta (Aβ) peptide evokes a depressive-like phenotype in rats. We tested the protective effects of AKBA in the mouse model of an Aβ-induced depressive-like phenotype. We evaluated the depressive-like behavior by using the tail suspension test (TST) and the splash test (ST). Behavioral analyses were accompanied by neurochemical quantifications, such as glutamate (GLU), kynurenine (KYN) and monoamines, and by biochemical measurements, such as glial fibrillary acid protein (GFAP), CD11b and nuclear factor kappa B (NF-kB), in mice prefrontal cortex (PFC) and hippocampus (HIPP). AKBA prevented the depressive-like behaviors induced by Aβ administration, since we recorded a reduction in latency to initiate self-care and total time spent to perform self-care in the ST and reduced time of immobility in the TST. Likewise, the increase in GLU and KYN levels in PFC and HIPP induced by the peptide injection were reverted by AKBA administration, as well as the displayed increase in levels of GFAP and NF-kB in both PFC and HIPP, but not in CD11b. Therefore, AKBA might represent a food supplement suitable as an adjuvant for therapy of depression in early-stage AD.
Biomolecules. 2021 May;11(5):.
PMID: 34063630 [PubMed - indexed for MEDLINE]
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35. |
Boswellia serrata suppress fipronil-induced neuronal necrosis and neurobehavioral alterations via promoted inhibition of oxidative/inflammatory/apoptotic pathways.
Khafaga AF, El-Kazaz SE, Noreldin AE
Boswellic acid (BA) is a pentacyclic terpenoid derived from the gum-resin of Boswellia serrate. It is known for its strong antioxidant, anti-inflammatory, and anticancer properties. It has improved spatial learning and provides neuroprotection against trimethyltin-induced memory impairment. The aim of this study is to evaluate the possible neuroprotective activity of B. serrata extract (BSE) containing BA against fipronil (FPN)-induced neurobehavioral toxicity in Wister male albino rats. Sixty male rats were allocated equally into six groups. The first group served as control; the second and third groups received BSE at two different oral doses (250 or 500 mg/kg body weight [BW], respectively). The fourth group was orally intoxicated with FPN (20 mg/kg BW), whereas the fifth and sixth groups served as preventive groups and co-treated with FPN (20 mg/kg BW) and BSE (250 or 500 mg/kg BW, respectively). The experiment was conducted over 8 weeks period. Results revealed that co-treatment with BSE led to significant (p > 0.05) dose-dependent reduction in malondialdehyde (MDA), nitric oxide (NO), interleukin-6 (IL6), tumor necrosis factors-alpha (TNF-α), nuclear factor Kappa-B (NF-κB), Cyclooxegenase-2 (COX-2), prostaglandin E2 (PGE2), serotonin, and acetylcholine (ACh). Conversely, significant (p > 0.05) up regulation of catalase (CAT), glutathione peroxidase (GSH-Px), gamma-aminobutyric acid (GABA), and acetylcholine esterase (AChE) has reported in BSE-co-treated groups. In addition, significant (p > 0.05) promotion in neurobehaviours, histopathologic imaging of the cerebral, cerebellar, and hippocampal regions, and immunohistochemical expression of caspase-3 and glial fibrillary acidic protein (GFAP) were also reported in the BSE-treated groups in a dose-dependent manner. In conclusion, BSE (500 mg/kg BW) is a natural, promising neuroprotective agent that can mitigate FPN-induced neurobehavioral toxicity via the suppression of oxidative, inflammatory, and apoptotic pathways and relieve neuronal necrosis and astrogliosis.
Sci Total Environ. 2021 Sep;785():147384.
PMID: 33933775 [PubMed - indexed for MEDLINE]
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36. |
Identification of Potential Antiseizure Agents in using Zebrafish and Mouse Epilepsy Models.
Brillatz T, Jacmin M, Queiroz EF, Marcourt L, Morin H, Shahbazi N, Boulens N, Riva A, Crawford AD, Allémann E, Wolfender JL
The resin of the tree Flueck. (synonym: ; Burseraceae), also known as "frankincense", is a traditional remedy used for central nervous system disorders in East Africa. Here we report the evaluation of its antiseizure activity in zebrafish and mouse epilepsy models to identify novel antiseizure compounds. The resin was extracted by solvents of increasing polarity. The hexane extract demonstrated the strongest antiseizure activity and was therefore subjected to bioactivity-guided isolation, which leaded to the isolation of eight terpene derivatives. A new prenylbicyclogermacrene derivative () was isolated along with seven other compounds (, -). Among them, the triterpene β-boswellic acid () showed the strongest activity and reduced 90% of pentylenetetrazole (PTZ)-induced seizures at 100 μg/mL. In parallel to , a commercial extract of was also evaluated and showed moderate bioactivity (45% reduction at 30 μg/mL). The extract of was subjected to targeted isolation of other boswellic acid derivatives (-), which were evaluated for antiseizure activity in comparison with . In the whole series, β-boswellic acid () was the most active (60% reduction at 200 μM), and its potency was also confirmed with its purchased standard (). Pure nanoparticles of and a commercially formulated extract of were tested in a PTZ-kindling mouse seizure model. This notably revealed that the administration reduced seizures by 50% in this mouse model, which was consistent with its detection and quantification in plasma and brain samples. This study and the preclinical evaluation performed indicate that β-boswellic acid, common to various species of , has some potential as an antiseizure agent.
ACS Chem Neurosci. 2021 May;12(10):1791-1801.
PMID: 33926190 [PubMed - indexed for MEDLINE]
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37. |
Alzheimer's disease improved through the activity of mitochondrial chain complexes and their gene expression in rats by boswellic acid.
Mohamed TM, Youssef MAM, Bakry AA, El-Keiy MM
The foremost neurodegenerative disease is Alzheimer's (AD), which is characterized as a gradual decrease in memory, cognitive function, and also personal changes occurred. This study aims to assess the role of boswellic bioactive component in control Alzheimer's disease through enhancing mitochondrial electron transport chain complexes in the rat model. Rats were divided into five equal groups: the control group (G1), boswellic acid control group (G2), AD disease group (G3), boswellic acid -pre-treated group (G4) and boswellic acid-treated group (G5). At the end of the experiment, blood glucose level, tau protein, different neurochemicals parameters (dopamine, acetylcholine), L-malondialdehyde (MDA) levels, and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities was determined. Also, GLUT2 and mitochondrial electron transport chain complexes were evaluated. As a result, an increase in hippocampus glucose, tau protein expression, MDA and GLUT2 in the AD group (G3) compared to control groups (G1 and G2) has been recorded. These parameters were declined after pre (G4) and treated (G5) by boswellic acid. The neurochemicals, antioxidants parameters, four mitochondrial chain complexes activities and their gene expression in the hippocampus of the AD group were decreased compared to the control groups (G1 and G2). In contrast, pre and treated groups by boswellic acid (G4 and G5, respectively) have shown an increase in antioxidants parameters, and the activities of four mitochondrial complexes, with the best improvement in the pre-treated group (G4), then treated group (G5). In conclusion; the boswellic acid improved the antioxidant and mitochondrial complexes in Alzheimer's disease.
Metab Brain Dis. 2021 Feb;36(2):255-264.
PMID: 33159653 [PubMed - indexed for MEDLINE]
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38. |
The effects of the combination of Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata on learning and memory deficit and oxidative damage in brain tissue of hypothyroid rats.
Saeri S, Hadjzadeh MA, Hosseini M, Hosseinian S, Arab Z
In the present study, the impact of a combination of four memory-enhancer herbs on cognitive impairment and brain tissue oxidative damage due to hypothyroidism was evaluated. Propylthiouracil (PTU; 0.05%) was administrated in drinking water. Rats were treated with a combination of four herbal products (Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata) mixed with honey at two doses (640 and 1,280 mg/kg) or donepezil (0.5 mg/kg), for 6 weeks. Memory performance on the Morris water maze (MWM) and avoidance behavior in passive avoidance was impaired by hypothyroidism, and brain tissue oxidative damage occurred. Herbal combination and donepezil significantly improved memory impairment, reduced malondialdehyde concentration, and nitric oxide metabolites while increased the thiol contents and catalase and superoxide dismutase enzymes activity in the brain. Our findings suggest that the mixture of herbal products improves learning and memory deficits caused by hypothyroidism, probably by reducing the brain tissue oxidative damage. PRACTICAL APPLICATIONS: Learning and memory impairment is a common feature of thyroid hormones deficiency. Several studies are showing that hypothyroidism in juvenile and mature rats induces significant cognitive impairment. Likewise, in humans, a close relationship between thyroid hormone deficiency and cognitive impairment has been reported. We used a mixture of herbal products, including Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata, to treat hypothyroidism-induced memory impairment. All these herbs are widely used as a food additive across the world. In Iranian traditional medicine, this herbal combination traditionally used to treat cognitive impairments. Numerous studies have indicated that these herbs show neuroprotective and memory-enhancing properties. Our finding indicated that a traditionally used herbal combination could potentially use as a treatment of cognitive impairment induced by thyroid hormone deficiency.
J Food Biochem. 2020 Sep;44(9):e13391.
PMID: 32696531 [PubMed - indexed for MEDLINE]
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39. |
The Effect of Beta-Boswellic Acid on the Expression of and Genes in the PC12 Cell Line.
Jebelli A, Khalaj-Kondori M, Rahmati-Yamchi M
Beta-boswellic acid (βBA) may play central roles in neural plasticity. Neural plasticity has significant implications for learning and memory which are governed by strict memoryrelated molecular pathways. To gain insight into the molecular mechanism by which βBA affects these pathways this study analyzed the expression patterns of and genes in PC12 cells treated with βBA. The cytotoxic effects of different βBA concentrations on PC12 cells were examined by MTT assay. For gene expression analysis, cells were treated with concentrations of 1 and 10 µM of βBA for 12, 24, 48, and 72 hours. Total RNA was purified by RNX-Plus solution and reverse transcribed into cDNA using Thermo Scientific Reverse Transcription reagents. The expression patterns of and genes were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). MTT assay indicated that βBA reduced PC12 cell viability in a time- and concentrationdependent manner. The 50% inhibitory concentrations for the 48 and 72 hours time points were 35 and 26 µM, respectively; while, the βBA concentrations up to 100 µM failed to kill 50% of the cells after 24 hours. According to the qRT-PCR data, the variant is not expressed in either βBA-treated or untreated PC12 cells. However, a significant upregulation was observed in after 12 hours of treatment with βBA, which followed by a significant downregulation after 24 hours and a persistent expression equal to the control until 72 hours. these findings indicate that PC12 cells not only does not express but also its expression cannot be induced by βBA. However, βBA does modulate the expression of . This result provides further insight into the molecular mechanism by which βBA affects memory.
Adv Pharm Bull. 2020 Jul;10(3):437-443.
PMID: 32665903 [PubMed - as supplied by publisher]
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40. |
PCL/gelatin scaffolds and beta-boswellic acid synergistically increase the efficiency of CGR8 stem cells differentiation into dopaminergic neuron: A new paradigm of Parkinson's disease cell therapy.
Kheradmand H, Babaloo H, Vojgani Y, Mirzakhanlouei S, Bayat N
Parkinson's disease is a progressive degenerative disorder in the central nervous system, which is distinguished by the death of dopamine-producing nerve cells. Levodopa, a dopamine precursor drug, is the current standard of care of symptomatic treatment for Parkinson's disease. However, the long-term use of the drug is associated with the development of motor fluctuations and dyskinesias. Cellular therapies aim to deploy fetal dopaminergic neurons as a means to replace the missing dopamine-producing cells. The present study aims to study the impact of beta-boswellic acid (BBA) coupled with poly ε-caprolactone (PCL)/gelatin scaffolds on the dopaminergic differentiation course of CGR8 embryonic stem cells (ESCs). For this purpose, CGR8 ESCs were cultured on PCL/gelatin scaffolds and a five-step protocol was employed to be promoted the neural differentiation of CGR8 ESCs. Gene expression analysis by real-time qPCR demonstrated that PCL/gelatin scaffolds along with BBA treatment impose synergistic effects on the derivation of dopaminergic-like cells from CGR8 ESCs. Reverse-phase high-performance liquid chromatography confirmed the functionality of the derived neurons by demonstrating the efficient secretion of dopamine in response to stimuli. Our results suggested that the generation of functional dopaminergic-like cells from CGR8 ESCs was increased and supported by PCL/gelatin scaffolds and BBA treatment can heighten the efficiency. The result of this study may open insight into Parkinson's disease cell therapy and provide future directions for tissue engineering aimed at the treatment of Parkinson's disease.
J Biomed Mater Res A. 2021 Apr;109(4):562-571.
PMID: 32588502 [PubMed - indexed for MEDLINE]
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41. |
Ten undescribed cembrane-type diterpenoids from the gum resin of Boswellia sacra and their biological activities.
Wang JJ, Sun HR, Suo XY, Xue Wang , Sun H, Wang XL, Jiang JD, Ji TF
Ten undescribed cembrane-type diterpenes boscartins AL-AU, as well as five known analogues were isolated from Boswellia sacra Flueck. The relative configurations of these boscartins were established by extensive spectroscopic analysis of NMR spectra, IR and MS. The absolute configurations of boscartin AL, boscartin AN and isoincensole oxide were unequivocally assigned by single crystal X-ray diffraction. Meanwhile, the absolute configurations of boscartin AM, boscartin AP and boscartin AQ were determined by an empirical in situ formed Rh-complex ECD method. Biological evaluations showed that four compounds exhibited obvious hepatoprotective activities against paracetamol-induced HepG2 cell damage at 10 μM. Regarding neuroprotective activity, some isolates displayed moderate to evident protective effects against glutamate-induced toxicity in primary cultured fetal rat cortical neurons or oxygen-glucose deprivation toxicity in SK-N-SH Cells at 10 μM.
Phytochemistry. 2020 Sep;177():112425.
PMID: 32535347 [PubMed - indexed for MEDLINE]
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42. |
Genus as a new candidate for neurodegenerative disorders.
Rajabian A, Sadeghnia H, Fanoudi S, Hosseini A
Neurodegenerative diseases, characterized by progressive loss of neurons, share common mechanisms such as apoptotic cell death, mitochondrial dysfunction, inflammation, and oxidative stress. Genus is a genus in the Burseraceae family. It comprises several species traditionally used for treatment of chronic inflammatory diseases, cerebral edema, chronic pain syndrome, gastrointestinal diseases, tumors, as well as enhancing intelligence. Many studies have been carried out to discover therapeutic approaches for neurodegenerative diseases such as Alzheimer's diseases, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis, stroke, and concomitant cognitive deficits. However, no curative treatment has been developed. This paper provides an overview of evidence about the potential of the Boswellia species and their main constituents, boswellic acids, as modulators of several mechanisms involved in the pathology of the neurodegenerative diseases. , animal, and clinical studies have confirmed that Boswellia species contain bioactive components that may enhance cognitive activity and protect against neurodegeneration. They exert the beneficial effects via targeting multiple pathological causes by antioxidative, anti-inflammatory, antiamyloidogenic, and anti-apoptotic properties. The Boswellia species, having neuroprotective potential, makes them a promising candidate to cure or prevent the neurodegenerative disorders.
Iran J Basic Med Sci. 2020 Mar;23(3):277-286.
PMID: 32440312 [PubMed - as supplied by publisher]
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43. |
Frankincense and myrrh and their bioactive compounds ameliorate the multiple myeloma through regulation of metabolome profiling and JAK/STAT signaling pathway based on U266 cells.
Gao R, Miao X, Sun C, Su S, Zhu Y, Qian D, Ouyang Z, Duan J
BACKGROUND: Frankincense and myrrh are used as traditional anti-inflammatory and analgesic medicines in China. It has been reported that frankincense and myrrh have significant anti-tumor activities. The present study was designed to investigate the inhibitory efficacy of frankincense ethanol extracts (RXC), myrrh ethanol extracts (MYC), frankincense -myrrh ethanol extracts (YDC), frankincense -myrrh water extracts (YDS) and their main compounds on U266 human multiple myeloma cell line.
METHODS: The inhibition effects of cell proliferation was evaluated by MTT assays. Cell culture supernatant was collected for estimation of cytokines. Western blot analysis was designed to investigate the regulatory of JAK/STAT signal pathway. In addition, cell metabolomics based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) had been established to investigate the holistic efficacy of frankincense and myrrh on U266 cells. Acquired data were processed by partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) to identify potential biomarkers.
RESULTS: RXC, MYC significantly inhibited the proliferation of U266 cells at dose of 25-400 μg/mL, YDC and YDS at the dose of 12.5-400 μg/mL. 3-O-acetyl-α-boswellic acid, 3-acetyl-11 keto-boswellic acid and 11-keto-boswellic acid had the most significant anti- multiple myeloma activities in the 10 compounds investigated, therefore these 3 compounds were selected as representatives for Elisa assay and western blotting experiments. All the extracts and active compounds ameliorated the secretion of cytokines and down-regulated the expression of JAK/STAT signaling pathway-related proteins. Comparing RXC, MYC, YDC and YDS-treated U266 cells with vehicle control (DMSO), 13, 8, 7, 7 distinct metabolites and 2, 2, 3, 0 metabolic target pathways involved in amino acid metabolism, lipid metabolism, vitamin metabolism, arachidonic acid were identified, respectively.
CONCLUSIONS: Taken together our results suggest that the frankincense and myrrh and their bioactive compounds inhibit proliferation of U266 multiple myeloma cells by regulating JAK/STAT signaling pathway and cellular metabolic profile.
BMC Complement Med Ther. 2020 Mar;20(1):96.
PMID: 32293402 [PubMed - indexed for MEDLINE]
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44. |
Acetyl-11-keto-β-boswellic acid ameliorates cognitive deficits and reduces amyloid-β levels in APPswe/PS1dE9 mice through antioxidant and anti-inflammatory pathways.
Wei C, Fan J, Sun X, Yao J, Guo Y, Zhou B, Shang Y
Alzheimer's disease (AD) is a complex disease involved oxidative stress and inflammation in its pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid compound from extracts of Boswellia serrata, which has been widely used as an antioxidant and anti-inflammatory agent. The present study was to determine whether AKBA, a novel candidate, could protect against cognitive and neuropathological impairments in AD. We found that AKBA treatment resulted in a significant improvement of learning and memory deficits, a dramatic decrease in cerebral amyloid-β (Aβ) levels and plaque burden, a profound alleviation in oxidative stress and inflammation, and a marked reduction in activated glial cells and synaptic defects in the APPswe/PS1dE9 mice. Furthermore, amyloid precursor protein (APP) processing was remarkably suppressed with AKBA treatment by inhibiting beta-site APP cleaving enzyme 1 (BACE1) protein expression to produce Aβ in the APPswe/PS1dE9 mice brains. Mechanistically, AKBA modulated antioxidant and anti-inflammatory pathways via increasing nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and via declining phosphorylation of inhibitor of nuclear factor-kappa B alpha (IκBα) and p65. Collectively, our findings provide evidence that AKBA protects neurons against oxidative stress and inflammation in AD, and this neuroprotective effect involves the Nrf2/HO-1 and nuclear factor-kappa B (NF-κB) signaling pathways.
Free Radic Biol Med. 2020 Apr;150():96-108.
PMID: 32109514 [PubMed - indexed for MEDLINE]
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45. |
11-Keto-β-Boswellic Acid Attenuates Glutamate Release and Kainic Acid-Induced Excitotoxicity in the Rat Hippocampus.
Lu CW, Lin TY, Wang SJ
Excessive glutamate concentration induces neuronal death in acute brain injuries and chronic neurodegenerative diseases. Natural compounds from medicinal plants have attracted considerable attention for their use in the prevention and treatment of neurological disorders. 11-Keto--boswellic acid, a triterpenoid found in the medicinal plant , has neuroprotective potential. The present study investigated the effect of 11-keto--boswellic acid on glutamate release and kainic acid-induced glutamate excitotoxicity in the rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), 11-keto--boswellic acid dose-dependently inhibited 4-aminopyridine-stimulated glutamate release. This effect was dependent on extracellular calcium, persisted in the presence of the glutamate transporter inhibitor DL-threo--benzyloxyaspartate, and was blocked by the vesicular transporter inhibitor bafilomycin A1. In addition, 11-keto--boswellic acid reduced the 4-aminopyridine-induced increase in intrasynaptosomal Ca levels. The N- and P/Q-type channel blocker -conotoxin MVIIC and the protein kinase A inhibitor H89 significantly suppressed the 11-keto--boswellic acid-mediated inhibition of glutamate release, whereas the intracellular Ca-releasing inhibitors dantrolene, CGP37157, and xestospongin C, mitogen-activated protein kinase inhibitor PD98059, as well as protein kinase C inhibitor calphostin C had no effect. In a rat model of excitotoxicity induced by intraperitoneal kainic acid injection (15 mg/kg), intraperitoneal 11-keto--boswellic acid administration (10 or 50 mg/kg) 30 min before kainic acid injection considerably ameliorated kainic acid-induced glutamate concentration elevation and CA3 neuronal death. These data suggested that 11-keto--boswellic acid inhibits glutamate release from the rat hippocampal synaptosomes by suppressing N- and P/Q-type Ca channels and protein kinase A activity, as well as exerts protective effects against kainic acid-induced excitotoxicity .
Planta Med. 2020 Apr;86(6):434-441.
PMID: 32097973 [PubMed - indexed for MEDLINE]
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46. |
3--Acetyl-11-keto- -boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma.
Li W, Ren L, Zheng X, Liu J, Wang J, Ji T, Du G
Glioblastoma is the most common and aggressive primary tumor in the central nervous system, accounting for 12%-15% of all brain tumors. 3--Acetyl-11-keto--boswellic acid (AKBA), one of the most active ingredients of gum resin from Birdw., was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma. However, whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear. An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA. The effects of AKBA on tumor growth were evaluated using MRI. The effects on the alteration of metabolic landscape were detected by MALDI-MSI. The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence, respectively. Transmission electron microscope was used to check morphology of cells treated by AKBA. Our results showed that AKBA (100 mg/kg) significantly inhibited the growth of orthotopic U87-MG gliomas. Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma, while immunoblot assays revealed that AKBA suppressed the expression of ATG5, p62, LC3B, p-ERK/ERK, and P53, and increased the ratio of p-mTOR/mTOR. Taken together, these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy. AKBA could be a promising chemotherapy drug for glioblastoma.
Acta Pharm Sin B. 2020 Feb;10(2):301-312.
PMID: 32082975 [PubMed - as supplied by publisher]
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47. |
Kinetic and thermodynamic study of beta-Boswellic acid interaction with Tau protein investigated by surface plasmon resonance and molecular modeling methods.
Haghaei H, Aref Hosseini SR, Soltani S, Fathi F, Mokhtari F, Karima S, Rashidi MR
Beta-Boswellic acid (BBA) is a pentacyclic terpene which has been obtained from frankincense and its beneficial effects on neurodegenerative disorders such as Alzheimer's disease (AD) have been addressed. In the present study, thermodynamic and kinetic aspects of BBA interaction with Tau protein as one of the important proteins involved in AD in the absence and presence of glucose has been investigated using surface plasmon resonance (SPR) method. Tau protein was immobilized onto the carboxy methyl dextran chip and its binding interactions with BBA were studied at physiological pH at various temperatures. Glucose interference with these interactions was also investigated. Results showed that BBA forms a stable complex with Tau (K=8.45×10 M) at 298 K. Molecular modeling analysis showed a hydrophobic interaction between BBA and HVPGGG segment of R and R repeated domains of Tau. The binding affinity increased by temperature enhancement, while it decreased significantly in the presence of glucose. Both association and dissociation of the BBA-Tau complex were accompanied with an entropic activation barrier; however, positive enthalpy and entropy changes revealed that hydrophobic bonding is the main force involved in the interaction.
Bioimpacts. 2020;10(1):17-25.
PMID: 31988853 [PubMed - as supplied by publisher]
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48. |
3-Acetyl-11-keto-β-boswellic acid attenuated oxidative glutamate toxicity in neuron-like cell lines by apoptosis inhibition.
Rajabian A, Sadeghnia HR, Hosseini A, Mousavi SH, Boroushaki MT
3-Acetyl-11-keto-β-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P < .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens (P < .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death.
J Cell Biochem. 2020 Feb;121(2):1778-1789.
PMID: 31642100 [PubMed - indexed for MEDLINE]
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49. |
Loading AKBA on surface of silver nanoparticles to improve their sedative-hypnotic and anti-inflammatory efficacies.
Khan A, Al-Harrasi A, Rehman NU, Sarwar R, Ahmad T, Ghaffar R, Khan H, Al-Amri I, Csuk R, Al-Rawahi A
Acetyl-11-keto--boswellic acid (AKBA) is a potent anti-inflammatory compound limited by its low water solubility and bioavailability. To load AKBA on silver nanoparticles (AgNPs) to improve bioavailability and water solubility of the compound. AKBA-AgNPs were chemically synthesized and characterized by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. AKBA and AKBA-Ag were studied for their sedative-hypnotic and anti-inflammatory efficacies. Pretreatment with AKBA or AKBA-Ag caused significant dose-dependent sedative-hypnotic effects at 5 and 10 mg/kg intraperitoneal. The effects of AKBA-loaded AgNPs caused pronounced changes in mice compared with those of AKBA, and the AKBA-AgNPs demonstrated anti-inflammatory effects that were superior to those of AKBA. The loading of AKBA on nanoparticles improved its pharmacokinetic effects, and capacity for drug delivery.
Nanomedicine (Lond). 2019 Nov;14(21):2783-2798.
PMID: 31617445 [PubMed - indexed for MEDLINE]
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50. |
Acetyl-11-keto-β-boswellic acid regulates the repair of rat sciatic nerve injury by promoting the proliferation of Schwann cells.
Jiang X, Wang Y, Zhang B, Fei X, Guo X, Jia Y, Yu W
AIMS: This study aimed to study the effects of acetyl-11-keto-β-boswellic acid (AKBA) on the regeneration of injured peripheral nerves and the ability of the extracellular signal-regulated kinase (ERK) signaling pathway to regulate the proliferation of Schwann cells and the formation of myelin.
MAIN METHODS: A sciatic nerve crush injury model rats were randomly divided into the model control, low-, medium-, and high-dose AKBA groups. The repair of myelin damage was observed through Luxol Fast Blue staining and the expression of neurofilament-200 (NF200) protein was detected through immunohistochemical tests. The relative expression levels of ERK, Phosphorylated-ERK (p-ERK), c-Jun N-terminal Kinase (JNK), and Phosphorylated-JNK (p-JNK) proteins were detected in vitro in Schwann cells treated with AKBA. The effect of AKBA on P0 and P75 protein expression in Schwann cells was detected through siRNA-mediated ERK gene knockout.
KEY FINDINGS: AKBA promotes the repair of rat sciatic nerve injury by elevating the phosphorylation of the ERK signaling pathway and by regulating the proliferation and myelination of Schwann cells.
SIGNIFICANCE: This test can provide data support for AKBA to repair sciatic nerve injury, provide a theoretical basis for further revealing AKBA repair mechanism, and provide reference for clinical development of sciatic nerve injury drugs.
Life Sci. 2020 Aug;254():116887.
PMID: 31606377 [PubMed - indexed for MEDLINE]
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51. |
The Effects of Frankincense Essential Oil on Stress in Rats.
Okano S, Honda Y, Kodama T, Kimura M
Frankincense essential oil, obtained from Boswellia carteri, is a popular essential oil, which is widely used in many parts of the world. While some of its properties are known, its effects on stress and sleep have not been studied. The effects of frankincense essential oil and its major components, limonene and α-pinene, on plasma corticosterone and glutathione (GSH) levels, as well as on sleep and wakefulness behaviour, were studied in sleep-deprived rats. The substances were applied topically after dilution in jojoba oil (vehicle). As compared to vehicle, frankincense essential oil at a dilution of 1/1000 (1:10) significantly reduced corticosterone levels (p < 0.05). In contrast, its major constituents (α-pinene and limonene), elevated levels of this stress hormone. Frankincense, limonene and α-pinene, all led to significant reductions in plasma GSH levels. Although frankincense dose-dependently reduced plasma concentrations of antioxidant ions albeit to levels insufficient to neutralize oxidative stress; levels of products of oxidative metabolism metabolites were decreased by the frankincense. In sleep-deprived rats, frankincense 1:10 respectively increased and decreased the amount of wakefulness and non-rapid eye movement sleep. Frankincense essential oil can counter the effects of stress by effectively relieving sleep debt and maintaining antioxidant capacity without increasing oxidative stress, and, therefore, may be beneficial in the management of stress.
J Oleo Sci. 2019;68(10):1003-1009.
PMID: 31582666 [PubMed - indexed for MEDLINE]
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52. |
A bioinspired 3D shape olibanum-collagen-gelatin scaffolds with tunable porous microstructure for efficient neural tissue regeneration.
Ghorbani F, Zamanian A, Kermanian F, Shamoosi A
There are a number of procedures for regeneration of injured nerves; however, tissue engineering scaffolds seems to be a promising approach for recovery of the functionality of the injured nerves. Consequently, in this study, olibanum-collagen-gelatin scaffolds were fabricated by freeze-cast technology. For this purpose, the olibanum and collagen were extracted from natural sources. The effect of solidification gradient on microstructure and properties of scaffolds was investigated. Scanning electron microscopy micrographs showed the formation of lamellar-type microstructure in which the average pore size reduced with an increase in freezing rate. According to the results, the prepared scaffolds at lower freezing rate showed a slight reduction in mechanical strength while the swelling and biodegradation ratio were increased due to the presence of larger pores and unidirectional channels. The composition of scaffolds and oriented microstructure improved cellular interaction. In addition, scaffolds with lower freezing rate exhibited promising results in terms of adhesion, spreading, and proliferation. In brief, the synthesized scaffolds at lower solidification rate have the potential for more in vitro and in vivo analyses to regeneration of neural defects.
Biotechnol Prog. 2020 Jan;36(1):e2918.
PMID: 31576679 [PubMed - indexed for MEDLINE]
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53. |
Beta-Boswellic Acid and Ethanolic Extract of Olibanum Regulating the Expression Levels of and Genes.
Jebelli A, Khalaj-Kondori M, Bonyadi M, Hosseinpour Feizi MA, Rahmati-Yamchi M
Physiological studies confirm improvement of memory by Olibanum, a resin from species, while little is known about the molecular mechanism by which it affects memory performance. Two master transcription factors, CREB-1 and CREB-2, regulate downstream memory-related genes expression, leading to the long-term memory potentiation. This study addresses the effects of Beta-boswellic acid (β-BA), the main ingredient of Olibanum, and ethanolic extract of the resin from on the expression of and genes in B65 cell line. B65 cells were treated with β-BA or ethanolic extract of Olibanum in different doses and time intervals and the cell viability/toxicity was measured by MTT assay. Total RNA was extracted from the treated and untreated control cells and cDNA was synthesized. The expression levels of and genes were quantified by Real-time PCR. MTT assays revealed 50% inhibitory concentrations of 42.05, 29.63, and 21.78 μg/mL for ethanolic extract of Olibanum and 89.54, 44.05, and 21.12 µM for β-BA at 24, 48, and 72 h time intervals respectively. Both β-BA and ethanolic extract of Olibanum altered and gene expression levels in time-dependent but not in dose-dependent way. However, β-BA showed stronger and more stable effects. The expression levels of the both genes followed an alternate upregulation and downregulation pattern, but in opposite directions, in response to the both solutions with the progress of time. These results suggest that Olibanum possibly improves memory performance, at least partially, by regulating the levels of CREB-1 and CREB-2 transcription factors via positive/negative-feedback loops.
Iran J Pharm Res. 2019;18(2):877-886.
PMID: 31531070 [PubMed - as supplied by publisher]
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54. |
Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion.
Ahmad S, Khan SA, Kindelin A, Mohseni T, Bhatia K, Hoda MN, Ducruet AF
Brain endothelial cells play an important role in maintaining blood flow homeostasis in the brain. Cerebral ischemia is a major cause of endothelial dysfunction which can disrupt the blood-brain barrier (BBB). Oxygen-glucose deprivation (OGD)/reperfusion promote cell death and BBB breakdown in brain endothelial cells. Acetyl-11-keto-β-boswellic acid (AKBA), a biologically active phytoconstituent of the medicinal plant Boswellia serrata, has been shown to be protective against various inflammatory diseases as well as ischemic brain injury. The molecular mechanisms underlying these beneficial characteristics of AKBA are poorly understood. We subjected bEND.3 cells to OGD/reperfusion to investigate the protective role of AKBA in this model. We found that AKBA treatment attenuated endothelial cell death and oxidative stress assessed by means of TUNEL assay, cleaved-caspase-3, and dihydroethidium (DHE) staining. Furthermore, OGD downregulated tight junction proteins ZO-1 and Occludin levels, and increased the expressions of inflammatory cytokines TNF-α, ICAM-1, and complement C3a receptor (C3aR). We also noticed the increased phosphorylation of ERK 1/2 in bEND.3 cells in OGD group. AKBA treatment significantly attenuated expression levels of these inflammatory proteins and prevented the degradation of ZO-1 and Occludin following OGD. In conclusion, AKBA treatment provides protection against endothelial cell dysfunction following OGD by attenuating oxidative stress and inflammation.
Neuromolecular Med. 2019 Dec;21(4):505-516.
PMID: 31515728 [PubMed - indexed for MEDLINE]
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55. |
Effects of resin extract on motor dysfunction and brain oxidative stress in an experimental model of Parkinson's disease.
Doaee P, Rajaei Z, Roghani M, Alaei H, Kamalinejad M
OBJECTIVE: oleo-gum resin (frankincense) exerted antioxidant and anti-inflammatory effects against several diseases, such as; asthma, rheumatoid arthritis and irritable bowel syndrome. In the current study, the influences of resin extract on motor dysfunction and oxidative stress markers were investigated in the intrastriatal 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD).
MATERIALS AND METHODS: The animals were randomly assigned to sham, lesion (6-OHDA), and three lesion groups treated with ethyl alcoholic extract of at doses of 125, 250 and 500 mg/kg for 3 weeks. The neurotoxin 6-OHDA (12.5 µg) was microinjected into the left striatum to induce PD in male rats. Motor behavior was assessed by rotational and elevated narrow beam tests. Oxidative stress markers were measured in striatal and midbrain homogenates.
RESULTS: There was a significant increase in contralateral rotations in 6-OHDA group versus sham group (p<0.001), and treatment with resin extract at doses of 125 and 250 mg/kg significantly decreased the rotations in comparison to 6-OHDA group (p<0.001 and p<0.001, respectively). The 6-OHDA group also showed considerable elevation in the latency to initiate crossing (p<0.001) and the total time (p<0.001) on narrow beam test. Moreover, treatment with extract at doses of 125, 250 and 500 mg/kg caused a significant reduction in the latency and total time (p<0.001, p<0.001, and p<0.01, respectively). Biochemical analysis showed no significant difference in oxidative stress markers levels among the groups.
CONCLUSION: Our findings suggest that resin extract acts as an anti-inflammatory and antioxidant agent that protects nigrostriatal dopaminergic neurons and improve motor impairments in PD.
Avicenna J Phytomed. 2019;9(3):281-290.
PMID: 31143695 [PubMed - as supplied by publisher]
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56. |
Evidence for the involvement of a GABAergic mechanism in the effectiveness of natural and synthetically modified incensole derivatives in neuropharmacological disorders: A computational and pharmacological approach.
Al-Harrasi A, Khan A, Rehman NU, Al-Shidhani S, Karim N, Khan I, Halim SA, Al-Rawahi A, Hussain J, Csuk R
In the course of our continuing exploration for novel bioactive lead compounds (s) from the species Boswellia, we have recently reported incensole derivatives isolated from Boswellia papyrifera Hochst. Given the known antidepressant-like effects of incensole and incensole acetate, we herein present that the low dose intraperitoneal administration of incensole derivatives, namely, incensfuran and incensone, showed significant antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST). Furthermore, these compounds were evaluated for their anxiolytic potential in the elevated plus maze (EPM) and light dark box (LDB) tests and anticonvulsant effects in pentylenetetrazole (PTZ)-induced seizure tests. In the EPM test, administration of these compounds led to dose-dependent increases in open arm entries and in the time spent in EPM open arms. Similar results were obtained in the LDB test, wherein compounds these caused significant increases in the number of transitions between lit and dark compartments and the time spent in the lit compartment. The anxiolytic-like effects in the EPM were not reversed by pretreatment with flumazenil, whereas PTZ and bicuculline (BIC) completely abolished the anxiolytic effects, showing the involvement of the non-benzodiazepine binding sites of GABA receptors. All four compounds induced significantly elevated brain GABA levels, indicating the involvement of a GABAergic mechanism. Additionally, molecular docking was conducted to elucidate the mode of action for the anxiolytic and anticonvulsant effects of these derivatives. Moreover, these compounds also possess drug-like properties and excellent ADMET profiles.
Phytochemistry. 2019 Jul;163():58-74.
PMID: 31015070 [PubMed - indexed for MEDLINE]
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57. |
Wound Healing Potential of the Standardized Extract of Boswellia serrata on Experimental Diabetic Foot Ulcer via Inhibition of Inflammatory, Angiogenetic and Apoptotic Markers.
Pengzong Z, Yuanmin L, Xiaoming X, Shang D, Wei X, Zhigang L, Dongzhou D, Wenjing Y, Jianbiao Y, Yang X, Xia L
The aim of the present study was to evaluate the wound healing potential and possible mechanism of action of the standardized extract of against the experimental model of diabetic foot ulcer. -Boswellic acid was isolated from the standardized extract of and characterized (HPLC, H-NMR, C-NMR, ESI-MS). Diabetes was induced in Sprague-Dawley rats by streptozotocin (55 mg/kg, i. p.), and wounds were created on the dorsal surface of the hind paw. (100, 200, and 400 mg/kg, p. o.) was administered to the rats for 16 days. The HPLC analysis showed a single peak with a retention time of 12.51 min. The compound was identified with ESI-MS [M + Na] = 455.37 as -boswellic acid. Treatment with (200 and 400 mg/kg) significantly increased the rate of wound contraction via modulation of oxido-nitrosative stress and elevated the hydroxyproline level at the wound area. reverse transcription-PCR analysis revealed that streptozotocin-induced increases in TNF-, interleukin-1, interleukin-6, nuclear factor-kappa-light-chain-enhancer of activated B cells, and Bcl-2-associated X protein, and decreases in angiopoietin-1, Tie2, transforming growth factor beta 1, vascular endothelial growth factor, and collagen-1 mRNA expression were significantly inhibited by . It also significantly reduced wound cellular necrosis as evaluated by flow cytometry using propidium iodide fluorescence intensity. Streptozotocin-induced histopathological alterations were also significantly ameliorated by . In conclusion, standardized extracts of exert its wound healing potential via orchestrating mechanisms, which include the inhibition of oxido-inflammatory markers (oxido-nitrosative stress, TNF-, interleukins, and nuclear factor-kappa-light-chain-enhancer of activated B cells), increased collagen synthesis (hydroxyproline and collagen-1) and angiogenesis (Ang-1/Tie2), promoting growth factors (transforming growth factor beta 1 and vascular endothelial growth factor), and inhibition of apoptosis (Bcl-2-associated X protein) to accelerate wound healing in experimental delayed diabetic foot ulcer.
Planta Med. 2019 May;85(8):657-669.
PMID: 30909313 [PubMed - indexed for MEDLINE]
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58. |
16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
Peterson CT, Sharma V, Iablokov SN, Albayrak L, Khanipov K, Uchitel S, Chopra D, Mills PJ, Fofanov Y, Rodionov DA, Peterson SN
The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
PLoS One. 2019;14(3):e0213869.
PMID: 30889210 [PubMed - indexed for MEDLINE]
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59. |
A Review of Herbal Therapy in Multiple Sclerosis.
Mojaverrostami S, Bojnordi MN, Ghasemi-Kasman M, Ebrahimzadeh MA, Hamidabadi HG
Multiple sclerosis is a complex autoimmune disorder which characterized by demyelination and axonal loss in the central nervous system (CNS). Several evidences indicate that some new drugs and stem cell therapy have opened a new horizon for multiple sclerosis treatment, but current therapies are partially effective or not safe in the long term. Recently, herbal therapies represent a promising therapeutic approach for multiple sclerosis disease. Here, we consider the potential benefits of some herbal compounds on different aspects of multiple sclerosis disease. The medicinal plants and their derivatives; Ginkgo biloba, Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Vaccinium macrocarpon, Nigella sativa,Piper methysticum, Crocus sativus, Panax ginseng, Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients.
Adv Pharm Bull. 2018 Nov;8(4):575-590.
PMID: 30607330 [PubMed - as supplied by publisher]
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60. |
Identification of a natural inhibitor of methionine adenosyltransferase 2A regulating one-carbon metabolism in keratinocytes.
Bai J, Gao Y, Chen L, Yin Q, Lou F, Wang Z, Xu Z, Zhou H, Li Q, Cai W, Sun Y, Niu L, Wang H, Wei Z, Lu S, Zhou A, Zhang J, Wang H
BACKGROUND: Psoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets with therapeutic potentials. Acetyl-11-keto-β-boswellic acid (AKBA) is the most bioactive ingredient of boswellic acids, a group of compounds with anti-inflammatory and anti-cancer properties. Target identification of AKBA and metabolomics analysis of psoriasis helped to elucidate the molecular mechanism underlying its effect, and provide new target(s) to treat the disease.
METHODS: To explore the targets and molecular mechanism of AKBA, we performed affinity purification, metabolomics analysis of HaCaT cells treated with AKBA, and epidermis of imiquimod (IMQ) induced mouse model of psoriasis and psoriasis patients.
FINDINGS: AKBA directly interacts with methionine adenosyltransferase 2A (MAT2A), inhibited its enzyme activity, decreased level of S-adenosylmethionine (SAM) and SAM/SAH ratio, and reprogrammed one‑carbon metabolism in HaCaT cells. Untargeted metabolomics of epidermis showed one‑carbon metabolism was activated in psoriasis patients. Topical use of AKBA improved inflammatory phenotype of IMQ induced psoriasis-like mouse model. Molecular docking and site-directed mutagenesis revealed AKBA bound to an allosteric site at the interface of MAT2A dimer.
INTERPRETATION: Our study extends the molecular mechanism of AKBA by revealing a new interacting protein MAT2A. And this leads us to find out the dysregulated one‑carbon metabolism in psoriasis, which indicates the therapeutic potential of AKBA in psoriasis. FUND: The National Natural Science Foundation, the National Program on Key Basic Research Project, the Shanghai Municipal Commission, the Leading Academic Discipline Project of the Shanghai Municipal Education Commission.
EBioMedicine. 2019 Jan;39():575-590.
PMID: 30591370 [PubMed - indexed for MEDLINE]
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61. |
Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells.
Seo EJ, Efferth T, Panossian A
BACKGROUND: Curcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients.
AIM: To elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS.
METHODS: We performed gene expression profiling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed), BS, and the combination of CC and BS (CC-BS; Curamin), followed by interactive pathways analysis of the regulated genes.
RESULTS: Treatment with CC and with CC-BS selectively downregulated opioid-related nociceptin receptor 1 gene (OPRL1) expression by 5.9-fold and 7.2-fold, respectively. No changes were detected in the other canonical opioid receptor genes: OPRK1, OPRD1, and OPRM1. Nociceptin reportedly increases the sensation of pain in supra-spinal pain transduction pathways. Thus, CC and CC-BS may downregulate OPRL1, consequently inhibiting production of the nociception receptor NOP, leading to pain relief. In neuroglia cells, CC and CC-BS inhibited signaling pathways related to opioids, neuropathic pain, neuroinflammation, osteoarthritis, and rheumatoid diseases. CC and CC-BS also downregulated ADAM metallopeptidase gene ADAMTS5 expression by 11.2-fold and 13.5-fold, respectively. ADAMTS5 encodes a peptidase that plays a crucial role in osteoarthritis development via inhibition of a corresponding signaling pathway.
CONCLUSION: Here, we report for the first time that CC and CC-BS act as nociceptin receptor antagonists, selectively downregulating opioid-related nociceptin receptor 1 gene (OPRL1) expression, which is associated with pain relief. BS alone did not affect OPRL1 expression, but rather appears to potentiate the effects of CC via multiple mechanisms, including synergistic interactions of molecular networks.
Phytomedicine. 2018 Nov;50():285-299.
PMID: 30466988 [PubMed - indexed for MEDLINE]
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62. |
Effects of 900-MHz radiation on the hippocampus and cerebellum of adult rats and attenuation of such effects by folic acid and .
Kivrak EG, Altunkaynak BZ, Alkan I, Yurt KK, Kocaman A, Onger ME
The radiation emitted from mobile phones has various deleterious effects on human health. This study was conducted to evaluate the effects of exposure to the 900-MHz radiation electromagnetic fields (EMF) emitted by mobile phones on Ammon's horn and the dentate gyrus (DG) in the hippocampus and cerebellum of male albino rats. We also investigated the neuroprotective effects of the antioxidants (BS) and folic acid (FA) against exposure to EMF. Twenty-four adult male rats were randomly divided into four groups of six animals each, an EMF group, an EMF + FA exposure group (EFA), an EMF + BS exposure group (EBS) and a control group (Cont). The EMF, EFA and EBS groups were exposed to 900-MHz EMF radiation inside a tube once daily over 21 days (60 min/day). The Cont group was not exposed to 900-MHz EMF. The results showed that EMF caused a significant decrease in total pyramidal and granular cell numbers in the hippocampus, and DG and in Purkinje cell numbers in the cerebellum in the EMF group compared to the other groups (p < 0.05). BS and FA attenuated the neurodegenerative effects of EMF in the hippocampus and cerebellum. Significant differences were also determined between the numbers of neurons in the EFA and EMF groups, and between the EBS and EMF groups (p < 0.05). However, there were no significant differences among Cont, EFA and EBS (p > 0.05). Our results may contribute to ongoing research into the effects of 900-MHz EMF exposure. : BS, ; CA, cornu ammonis; CAT, catalase; CE, coefficient of error; CV, coefficient of variation; DG, dentate gyrus; DNA, deoxyribonucleic acid; EMF, electromagnetic field; EBS, the group that is exposed to EMF and received a single daily gavage of BS (500 mg/kg/day) during 21 days; EEG, electroencephalogram; EFA, the group that is exposed to EMF and received a single daily gavage of folic acid (50 mg/kg/day) during 21 days; FA, folic acid; gr, granular layer; HO, hydrogen peroxide; MHz, Megahertz; ml, molecular layer; RF, radiofrequency; ROS, reactive oxygen specimens; SEM, standard error of the mean.
J Microsc Ultrastruct. 2017;5(4):216-224.
PMID: 30023257 [PubMed - as supplied by publisher]
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63. |
Frankincense upregulates the hippocampal calcium/calmodulin kinase II-α during development of the rat brain and improves memory performance.
Beheshti S, Ghorbanpour Skakakomi A, Ghaedi K, Dehestani H
BACKGROUND: Frankincense is an oleo gum resin derived from trees of genus Boswellia. It has favorable effects on memory formation. However, the probable underlying molecular mechanisms have not been assessed. Frankincense exerts some of its effects via activation of protein kinases. Calcium/calmodulin kinaseII (CaMKII) and CaMKIV are crucial mediators of learning and memory. We studied the effect of maternal injection of the aqueous extract of frankincense during gestation and lactation periods on spatial memory performance and the mRNA expression levels of the hippocampal CaMKIIand CaMKIV in the offspring rats.
METHODS: Aqueous extract of Frankincense (50 and 100 mg/kg) or tap water was gavaged to distinct female rats during gestation and lactation periods. Memory performance was assessed in groups of male offspring using Morris water maze. In other groups of the offspring (with no memory test), the hippocampi of the juvenile rats were removed 30 days after labor. A real-time PCR method was used to measure the mRNA levels of CaMKII and CaMKIV.
RESULTS: Frankincense improved spatial memory retrieval in the offspring rats in a dose-dependent manner. The mRNA expression of hippocampal CaMKIV was unchanged between groups. However, the mRNA expression of hippocampal CaMKII was dose-dependently upregulated in the rats, whose mothers had received frankincense.
CONCLUSIONS: Due to the crucial role of the CaMKII in memory formation, the results provide a molecular basis for the effect of administration of frankincense to mother rats on improvement of the memory in the offspring.
Int J Dev Neurosci. 2018 Oct;69():44-48.
PMID: 29966740 [PubMed - indexed for MEDLINE]
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64. |
Incensole acetate prevents beta-amyloid-induced neurotoxicity in human olfactory bulb neural stem cells.
El-Magd MA, Khalifa SF, A Alzahrani FA, Badawy AA, El-Shetry ES, Dawood LM, Alruwaili MM, Alrawaili HA, Risha EF, El-Taweel FM, Marei HE
β-Amyloid peptide (Aβ) is a potent neurotoxic protein associated with Alzheimer's disease (AD) which causes oxidative damage to neurons. Incensole acetate (IA) is a major constituent of Boswellia carterii resin, which has anti-inflammatory and protective properties against damage of a large verity of neural subtypes. However, this neuroprotective effect was not studied on human olfactory bulb neural stem cells (hOBNSCs). Herein, we evaluated this effect and studied the underlying mechanisms. Exposure to Aβ (5 and 10 μM for 24 h) inhibited proliferation (revealed by downregulation of Nestin and Sox2 gene expression), and induced differentiation (marked by increased expression of the immature neuronal marker Map2 and the astrocyte marker Gfap) of hOBNSCs. However, pre-treatment with IA (100 μM for 4 h) stimulated proliferation and differentiation of neuronal, rather than astrocyte, markers. Moreover, IA pretreatment significantly decreased the Aβ-induced viability loss, apoptotic rate (revealed by decreased caspase 3 activity and protein expression, downregulated expression of Bax, caspase 8, cyto c, caspase3, and upregulated expression of Bcl2 mRNAs and proteins, in addition to elevated mitochondrial membrane potential and lowered intracellular Ca). IA reduced Aβ-mediated ROS production (revealed by decreased intracellular ROS and MDA level, and increased SOD, CAT, and GPX contents), and inhibited Aβ-induced inflammation (marked by down-regulated expression of IL1b, TNFa, NfKb, and Cox2 genes). IA also significantly upregulated mRNA and protein expression of Erk1/2 and Nrf2. Notably, IA increased the antioxidant enzyme heme oxygenase-1 (HO-1) expression and this effect was reversed by HO-1 inhibitor zinc protoporphyrin (ZnPP) leading to reduction of the neuroprotective effect of IA against Aβ-induced neurotoxicity. These findings clearly show the ability of IA to initiate proliferation and differentiation of neuronal progenitors in hOBNSCs and induce HO-1 expression, thereby protecting the hOBNSCs cells from Aβ-induced oxidative cell death. Thus, IA may be applicable as a potential preventive agent for AD by its effect on hOBNSCs and could also be used as an adjuvant to hOBNSCs in cellular therapy of neurodegenerative diseases.
Biomed Pharmacother. 2018 Sep;105():813-823.
PMID: 29913410 [PubMed - indexed for MEDLINE]
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65. |
Acetyl-11-keto-β-boswellic acid extracted from promotes Schwann cell proliferation and sciatic nerve function recovery.
Jiang XW, Zhang BQ, Qiao L, Liu L, Wang XW, Yu WH
Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid (AKBA) is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1 day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index. Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore, for in vitro experiments, Schwann cells were treated with AKBA at 0-20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 (2.5 μL/mL), the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.
Neural Regen Res. 2018 Mar;13(3):484-491.
PMID: 29623934 [PubMed - as supplied by publisher]
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66. |
NEUROPROTECTIVE EFFECT OF BOSWELLIA SERRATA AND ITS ACTIVE CONSTITUENT ACETYL 11-KETO-β-BOSWELLIC ACID AGAINST OXYGEN-GLUCOSE-SERUM DEPRIVATION-INDUCED CELL INJURY.
Sadeghnia HR, Arjmand F, Ghorbani A
Oxidative stress plays a key role in pathophysiology of brain ischemia. This study aimed to test whether B. serrata hydroalcoholic extract (BSE) and its active constituent 3-acetyl-1 1-keto-β-boswellic acid (AKBA) could protect neurons against ischemic condition induced by oxygen, glucose and serum deprivation (OGSD). First, PC12 neural cells were incubated with BSE (0-400 pg/mL) or AKBA (0-40 pg/mL) for 24 h to find non-cytotoxic concentrations of BSE and AKBA. Then, the cells were pre- (for 2 h) and co-treated with 1.5-6 μg/mL BSE or 0.5-2.5 pg/mL AKBA, and then exposed to OGSD condition for 6 h. The IC50. values of BSE and AKBA were 95 and 12.2 μg/mL, respectively. BSE (3 and 6 pg/mL) and AKBA (1 and 2.5 pg/mL) significantly increased viability of ischemic cells, in a concertation-dependent manner. The levels of intracellular oxygen free radicals, lipid peroxidation and oxidative DNA damage were also significantly and concentration-dependently decreased following treatment of ischemic cells with BSE or AKBA. Using HPLC analysis, the mount of AKBA in a sample of BSE was found to be 9.2%. In conclusion, B. sernata and AKBA reduce neuronal cell death induced by OGSD and this neuroprotective effect is mediated via attenuation of oxidative stress.
Acta Pol Pharm. 2017 May;74(3):911-920.
PMID: 29513961 [PubMed - indexed for MEDLINE]
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67. |
Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity: - Neuroprotective effect of Boswellic acid.
Ebrahimpour S, Fazeli M, Mehri S, Taherianfard M, Hosseinzadeh H
OBJECTIVES: Boswellic acid (BA), a compound isolated from the gum-resin of , is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats.
METHODS: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex.
RESULTS: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group ( < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group ( < 0.01).
CONCLUSION: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.
J Pharmacopuncture. 2017 Mar;20(1):10-17.
PMID: 28392957 [PubMed - as supplied by publisher]
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68. |
Boswellia serrata gum resin aqueous extract upregulatesBDNF but not CREB expression in adult male rat hippocampus.
Khalaj-Kondori M, Sadeghi F, Hosseinpourfeizi MA, Shaikhzadeh-Hesari F, Nakhlband A, Rahmati-Yamchi M
BACKGROUND/AIM: Boswellia from the family Burseraceae has been proposed for prevention of amnesia; however, the molecular mechanism by which it affects memory is not clear. To reveal the potential molecular mechanism, the effects of boswellia on the expression of two memory related genes, CREB and BDNF, were investigated.
MATERIALS AND METHODS: Twenty-one male rats were randomly divided into 3 groups (n = 7): the control group received distilled water and the treatment groups received two doses of aqueous extract of Boswellia serrata gum resin (boswellia) (50 and 100 mg/kg) every day for 4 weeks. The animals were tested by the Morris water maze (MWM) and their hippocampus was isolated. Expression of CREB and BDNF genes was analyzed by Q-RT-PCR.
RESULTS: The MWM test showed improvement in spatial learning and memory in both treatment groups. Gene expression analysis revealed a significant increase in BDNF but not CREB expression in rats treated with both 50 and 100 mg/kg doses in comparison with the control group.
CONCLUSION: Although boswellia exerts its effects on memory formation at least partly by affecting the expression of BDNF, the results imply that boswellia probably affects memory via another BDNF-related pathway than the BDNF-CREB-BDNF cycle.
Turk J Med Sci. 2016 Nov;46(5):1573-1578.
PMID: 27966331 [PubMed - indexed for MEDLINE]
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69. |
Combined Administration of and Extracts in an Animal Model of Memory.
Mahboubi M, Taghizadeh M, Talaei SA, Takht Firozeh SM, Rashidi AA, Tamtaji OR
BACKGROUND: and is traditionally used for its memory enhancing effects.
OBJECTIVES: In this study, we evaluated the protective effects of combined form of these extracts on memory improvement of scopolamine treated rats by the Morris water maze method.
MATERIALS AND METHODS: Two groups (group 1 and 2) of animals were pretreated with combined extracts of and (200, 400 mg/Kg body weight) for four weeks and then, 30 minutes before starting the experiment scopolamine was injected (0.1 mg/kg body weight) intraperitoneally to pretreated animals. The control group was the animals that were injected by scopolamine and pre treated with distilled water (group 3). The normal group was treated with distilled water alone (group 4).
RESULTS: For time spent and distance, there was no substantial difference between groups 1, 2 and 4, while they had statistical difference with group 3 (P = 0.001). The spatial memory evaluation showed no significant difference between treated groups and normal group.
CONCLUSIONS: Therefore, the combination of the two extracts had the ability to improve memory as its traditional use.
Iran J Psychiatry Behav Sci. 2016 Sep;10(3):e681.
PMID: 27822272 [PubMed - as supplied by publisher]
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70. |
Chemical composition and biological activities of extracts and essential oil of Boswellia dalzielii leaves.
Kohoude MJ, Gbaguidi F, Agbani P, Ayedoun MA, Cazaux S, Bouajila J
CONTEXT: Boswellia dalzielii Hutch. (Burseraceae) is an aromatic plant. The leaves are used for beverage flavouring.
OBJECTIVE: This study investigates the chemical composition and biological activities of various extracts.
MATERIALS AND METHODS: The essential oil was prepared via hydrodistillation. Identification and quantification were realized via GC-MS and GC-FID. Consecutive extractions (cyclohexane, dichloromethane, ethyl acetate and methanol) were carried out and various chemical groups (phenolics, flavonoids, tannins, antocyanins and sugar) were quantified. The volatile compounds of organic extracts were identified before and after derivatization. Antioxidant, antihyperuricemia, anti-Alzheimer, anti-inflammatory and anticancer activities were evaluated.
RESULTS: In the essential oil, 50 compounds were identified, including 3-carene (27.72%) and α-pinene (15.18%). 2,5-Dihydroxy acetophenone and β-d-xylopyranose were identified in the methanol extract. Higher phenolic (315.97 g GAE/kg dry mass) and flavonoid (37.19 g QE/kg dry mass) contents were observed in the methanol extract. The methanol extract has presented remarkable IC=6.10 mg/L for antiDPPH, 35.10 mg/L for antixanthine oxidase and 28.01 mg/L for anti-5-lipoxygenase. For acetylcholinesterase inhibition, the best IC (76.20 and 67.10 mg/L) were observed, respectively, with an ethyl acetate extract and the essential oil. At 50 mg/L, the dichloromethane extract inhibited OVCAR-3 cell lines by 65.10%, while cyclohexane extract inhibited IGROV-1 cell lines by 92.60%.
DISCUSSION AND CONCLUSION: Biological activities were fully correlated with the chemical groups of the extracts. The ethyl acetate and methanol extracts could be considered as potential alternatives for use in dietary supplements for the prevention or treatment of diseases because of these extracts natural antioxidant, antihyperuricemic and anti-inflammatory activities.
Pharm Biol. 2017 Dec;55(1):33-42.
PMID: 27650786 [PubMed - indexed for MEDLINE]
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71. |
The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes.
Fathi E, Katouli FH, Riazi GH, Shasaltaneh MD, Parandavar E, Bayati S, Afrasiabi A, Nazari R
Reelin is an extracellular glycoprotein which contributes to synaptic plasticity and function of memory in the adult brain. It has been indicated that the Reelin signaling cascade participates in Alzheimer's disease (AD). Besides the neurons, glial cells such as astrocytes also express Reelin protein. While functional loss of astrocytes has been reported to be associated with AD, dysfunction of astrocytic Reelin signaling pathway has not received much attention. Therefore, we investigated the effects of α-boswellic acid (ABA) as one of the major component of Boswellia serrata resin on primary fetal human astrocytes under a stress paradigm as a possible model for AD through study on Reelin cascade. For this aim, we used streptozotocin (STZ), in which from an outlook generates Alzheimer's hallmarks in astrocytes, and assayed Reelin expression, Tau and Akt phosphorylation as well as reactive oxygen species (ROS) generation and apoptosis in the presences of ABA. Our results indicated that while STZ (100 µM) down-regulated the expression of Reelin, ABA (25 µM) up-regulated its expression (p < 0.01) for 24 h. ABA efficiently reduced hyperphosphorylated Tau (Ser404) in STZ-treated astrocytes (p < 0.01). Furthermore, STZ-induced apoptosis by increasing cleaved caspase three (p < 0.01) and ROS generation (p < 0.01), a further pathological hallmark of Tauopathy. On the other hand, ABA decreased ROS generation and promoted proliferation of astrocytes through elevating Survivin expression (p < 0.01). These results showed that ABA could be considered as a potent therapeutic agent for prevention and decreasing the progression of Alzheimer's hallmarks in astrocytes; however, more in vivo studies would be needed.
Neuromolecular Med. 2017 Mar;19(1):136-146.
PMID: 27567921 [PubMed - indexed for MEDLINE]
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72. |
Aqueous and Ethanolic Extracts of Boswellia serrata Protect Against Focal Cerebral Ischemia and Reperfusion Injury in Rats.
Forouzanfar F, Hosseinzadeh H, Ebrahimzadeh Bideskan A, Sadeghnia HR
Oxidative stress and cell apoptosis play major roles in neuronal injury after ischemia-reperfusion (I-R) injury. Boswellia serrata is a medicinal plant with antioxidant properties. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid compound from B. serrate. In the current study, the neuroprotective effects of aqueous and ethanolic extracts of B. serrata (named ABS and EBS, respectively) and AKBA were investigated against middle cerebral artery occlusion-induced cerebral I-R injury in rats. ABS and EBS with doses of 125, 250 and 500 and AKBA with a dose of 50 mg/kg were administered (intraperitoneally) just after middle cerebral artery occlusion induction for 30 min and reperfusion for 24 h. HPLC analysis suggested that ABS and EBS had AKBA of 8.8% and 9.5% (w/w), respectively. B. serrata and AKBA significantly improved neurological deficit and reduced brain infarction, neuronal cell loss and apoptosis and also attenuated lipid peroxidation while increasing glutathione content and superoxide dismutase activity in the cerebral cortex following a stroke. Apoptosis suppression was found to be mediated through regulating caspase-3 and bax/bcl-2 expressions. In conclusion, our results demonstrated that B. serrata and AKBA attenuate oxidative damage and inhibit cell apoptosis, subsequently protecting cerebral I-R injury in rats. Copyright © 2016 John Wiley & Sons, Ltd.
Phytother Res. 2016 Dec;30(12):1954-1967.
PMID: 27515127 [PubMed - indexed for MEDLINE]
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73. |
Boswellia serrata Protects Against Glutamate-Induced Oxidative Stress and Apoptosis in PC12 and N2a Cells.
Rajabian A, Boroushaki MT, Hayatdavoudi P, Sadeghnia HR
This study was designed to investigate whether the extract from Boswellia serrata oleo-gum resin (BSE) can protect against glutamate-induced oxidative damage and cytotoxicity in PC12 and N2a cell lines. Using a simple and reliable reverse-phase high-performance liquid chromatography (HPLC), the amount of 3-acetyl-11-keto-β-boswellic acid (AKBA) in the BSE was found to be 18.5% w/w. The results confirmed that BSE and AKBA, at concentrations as high as 100 μg/mL or 10 μM, respectively, caused no significant cytotoxicity or apoptotic cell death. Co- and pretreatment with BSE (25-100 μg/mL) or AKBA (5 μM) restored the viability of PC12 and N2a cells under glutamate toxicity (8 mM). Treatment with BSE and AKBA also attenuated the toxic effects of glutamate on intracellular reactive oxygen species, lipid peroxidation, superoxide dismutase activity, and oxidative DNA damage compared with the untreated glutamate-injured cells. Furthermore, BSE and AKBA decreased the apoptotic cell population in the sub-G1 region and the rate of both early and late-stage apoptosis induced by glutamate in the cells. Our data suggest that the protective effects of Boswellia extract and AKBA against glutamate toxicity in PC12 and N2a cells may be mediated through the amelioration of the oxidative stress and the resultant apoptosis.
DNA Cell Biol. 2016 Nov;35(11):666-679.
PMID: 27494534 [PubMed - indexed for MEDLINE]
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74. |
Beneficial effect of Boswellia serrata gum resin on spatial learning and the dendritic tree of dentate gyrus granule cells in aged rats.
Hosseini-Sharifabad M, Kamali-Ardakani R, Hosseini-Sharifabad A
OBJECTIVE: The hippocampal formation, particularly the dentate gyrus (DG), shows age-related morphological changes that could cause memory decline. It is indicated that Boswellia resins attenuates memory deficits and the major component of Boswellia serrata (Bs) gum resin, beta boswellic acid increased neurite outgrowth and branching in hippocampal neurons. This study was designed to investigate the effect of Boswellia treatment on spatial learning performance and the morphology of dentate granule cells in aged rats.
MATERIALS AND METHODS: Sixteen male Wistar rats (24 months old) were divided into experimental and control groups. Experimental group was intragastrically administered with the aqueous extract of Bs (100 mg/kg/d for 8 weeks) and control group received a similar volume of water. Spatial learning performance of rats was tested using Morris water maze task. At the end of experiment, the brain was removed and the right hippocampus was serially sectioned for morphometric analysis. The Cavalieri principle was employed to estimate the volume of the DG. A quantitative Golgi study was used to analyze the dendritic trees of dentate granule cells.
RESULTS: Chronic treatment with Bs improved spatial learning capability during the three acquisition days. Comparisons also revealed that Bs-treated aged rat had greater DG with increased dendritic complexity in the dentate granule cells than control rats. Hippocampal granule cells of Bs-treated aged rats had more dendritic segments, larger arbors, more numerical branching density and more dendritic spines in comparison to control animals.
CONCLUSION: This study provided a neuro-anatomical basis for memory improvement due to chronic treatment with Bs.
Avicenna J Phytomed. 2016;6(2):189-97.
PMID: 27222832 [PubMed - as supplied by publisher]
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75. |
Co-administration of 3-Acetyl-11-Keto-Beta-Boswellic Acid Potentiates the Protective Effect of Celecoxib in Lipopolysaccharide-Induced Cognitive Impairment in Mice: Possible Implication of Anti-inflammatory and Antiglutamatergic Pathways.
Sayed AS, El Sayed NS
Neuro-inflammation is known to initiate the underlying pathogenesis of several neurodegenerative disorders which may progress to cognitive, behavioral, and functional impairment. Boswellia serrata is a well-known powerful anti-inflammatory agent used to treat several inflammatory diseases. The aim of the current study is to investigate the effect of the combination therapy of 3-acetyl-11-keto-β-boswellic acid (AKBA), a 5-lipoxygenase (5-LOX) inhibitor and celecoxib, and a selective cyclooxygenase-2 (COX-2) inhibitor as dual enzyme inhibitors compared to monotherapies with celecoxib and AKBA. Cognitive dysfunction is induced by intraperational injection of lipopolysaccharide (LPS) in mice. Radial maze, Y maze, and novel object recognition (NOR) were performed to evaluate the possible behavioral changes. Moreover, estimation of glutamate and tumor necrosis factor-alpha (TNF-α), as well as an immunohistochemical investigation of amyloid beta peptide (Aβ) was performed to evaluate the molecular changes that followed the LPS or drug treatment. The results showed that the combination therapy of AKBA and celecoxib reversed the behavioral and molecular changes caused by LPS cognitive dysfunction model that predispose cognitive dysfunction in mice. This study showed the effectiveness of the dual therapy with AKBA and celecoxib as anti-inflammatory, antiglutamatergic, and anti-amyloidogenic agents in the management of cognitive dysfunction.
J Mol Neurosci. 2016 May;59(1):58-67.
PMID: 26984336 [PubMed - indexed for MEDLINE]
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76. |
Tongxinluo reduces brain edema and inhibits post-ischemic inflammation after middle cerebral artery occlusion in rats.
Cai M, Yu Z, Wang L, Song X, Zhang J, Zhang Z, Zhang W, Li W, Xiang J, Cai D
ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL), a widely used traditional Chinese medicine, has been proved multiple therapeutic effects in cerebral ischemic infraction. The purpose of this study was to investigate the protective effects of TXL on the brain edema and post-ischemic inflammatory response.
MATERIALS AND METHODS: Middle cerebral artery occlusion in the rat was used as the ischemia model. Rats were treated with TXL. In the first stage, the best dosage was chosen based on functional assessment and infarct size. In the second stage, rats were randomly divided into 5 groups: sham control (sham), ischemia and reperfusion (IR) 24h, TXL24h, I/R72h, TXL72h. TXL(1.6g/kg/day) administration was pre-performed for 3 days in TXL groups, and was post-performed for 24h (TXL24h group) or 72h (TXL72h group). Brain edema was measured by water content, MRI and AQP4 expression. Iba1, HMGB1, TLR4, NF-κB expression were examined by immunofluorescence staining or Western blot. TNF-α was determined by enzyme-linked immunosorbent assay.
RESULTS: High dose (1.6g/kg/day) of TXL remarkably reduced neurological deficit scores and cerebral infarct area. Compared with those results of I/R24h group, pre-post treatment with TXL for 3 days decreased brain water content, down-regulated AQP4 expression, lowered relative signal intensity of T2WI, reduced lesion volume ratio, and inhibited the activation of microglia, HMGB1, TLR4, NF-κB and TNF-α.
CONCLUSIONS: These results indicated that the TXL pre-post treatment for 3 days could be an effective therapy for brain ischemia by inhibiting the development of brain edema and post-ischemic inflammation.
J Ethnopharmacol. 2016 Apr;181():136-45.
PMID: 26805468 [PubMed - indexed for MEDLINE]
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77. |
Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways.
Ding Y, Qiao Y, Wang M, Zhang H, Li L, Zhang Y, Ge J, Song Y, Li Y, Wen A
Acetyl-11-keto-β-boswellic acid (AKBA), a main active constituent from Boswellia serrata resin, is a novel candidate for therapy of cerebral ischemia-reperfusion (I/R) injury. Nevertheless, its poor solubility in aqueous solvent, bioavailability, and rapid clearance limit its curative efficacy. To enhance its potency, in our study, AKBA-loaded o-carboxymethyl chitosan nanoparticle (AKBA-NP) delivery system was synthesized. The transmission electron microscopy and transmission electron microscope images of AKBA-NPs suggested that particle size was 132 ± 18 nm, and particles were spherical in shape with smooth morphology. In pharmacokinetics study, AKBA-NPs apparently increases the area under the curve of plasma concentration-time and prolonged half-life compared with AKBA. The tissue distribution study confirmed that AKBA-NPs had a better brain delivery efficacy in comparison with AKBA. The results from our pharmacodynamic studies showed that AKBA-NPs possess better neuroprotection compared with AKBA in primary neurons with oxygen-glucose deprivation (OGD) model and in animals with middle cerebral artery occlusion (MCAO) model. Additionally, AKBA-NPs modulate antioxidant and anti-inflammatory pathways more effectively than AKBA by increasing nuclear erythroid 2-related factor 2 and heme oxygenase-1 expression, and by decreasing nuclear factor-kappa B and 5-lipoxygenase expression. Collectively, our results suggest that AKBA-NPs serve as a potent delivery vehicle for AKBA in cerebral ischemic therapy.
Mol Neurobiol. 2016 Aug;53(6):3842-3853.
PMID: 26162321 [PubMed - indexed for MEDLINE]
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78. |
The effects of aqueous extract of Boswellia Serrata on hippocampal region CA1 and learning deficit in kindled rats.
Jalili C, Salahshoor MR, Pourmotabbed A, Moradi S, Roshankhah Sh, Darehdori AS, Motaghi M
Temporal lobe epilepsy (TLE) is a disorder of the central nervous system in which hippocampus is mostly involved and causes memory impairment. Kindling is a model of inducing epilepsy which is created through pentylenetetrazol (PTZ) administration. This study examines the role of the aqueous extract of Boswellia on the learning and development of brain (formation of dendritic branches and axons) of the PTZ-induced kindled rats. The study is conducted on sixty-four male rats divided into 8 groups. Kindling seizures are induced by three injections of 25 mg/kg of PTZ every 15 min. The aqueous extracts (0, 0.1, 0.5, 1 g/kg, i.p) are administrated to all animals for three consecutive days. Passive avoidance learning of animals is examined using shuttle box apparatus and step-through latency (STL) method. Rats are anesthetized and their brains are fixed by transcardial perfusion method and are analyzed by morphometric methods after applying Golgi and Cresyl violet staining methods. PTZ-induced kindling indicates a significant decrease in the number of pyramidal neurons and dendritic spines in hippocampal region cornu ammonis (CA1). The STL of the kindled rats is significantly reduced compared with control ones. Also, Boswellia extract dramatically increased the number of neuronal processes in CA1 region and improves passive-avoidance learning ability in both control and PTZ-kindled animals in 1 g/kg dose administration of Boswellia extract, especially at high doses can eliminate adverse effects of seizures on cognitive function in hippocampal area CA1 in rats.
Res Pharm Sci. 2014;9(5):351-8.
PMID: 25657807 [PubMed - as supplied by publisher]
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79. |
Posttreatment with 11-Keto-β-Boswellic Acid Ameliorates Cerebral Ischemia-Reperfusion Injury: Nrf2/HO-1 Pathway as a Potential Mechanism.
Ding Y, Chen M, Wang M, Li Y, Wen A
Oxidative stress is well known to play a pivotal role in cerebral ischemia-reperfusion injury. The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway has been considered a potential target for neuroprotection in stroke. 11-Keto-β-boswellic acid (KBA) is a triterpenoid compound from extracts of Boswellia serrata. The aim of the present study was to determine whether KBA, a novel Nrf2 activator, can protect against cerebral ischemic injury. Middle cerebral artery occlusion (MCAO) was operated on male Sprague-Dawley rats. KBA (25 mg/kg) applied 1 h after reperfusion significantly reduced infarct volumes and apoptotic cells as well as increased neurologic scores at 48 h after reperfusion. Meanwhile, posttreatment with KBA significantly decreased malondialdehyde (MDA) levels, restored the superoxide dismutase (SOD) activity, and increased the protein Nrf2 and HO-1 expression in brain tissues. In primary cultured astrocytes, KBA increased the Nrf2 and HO-1 expression, which provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. But knockdown of Nrf2 or HO-1 attenuated the protective effect of KBA. In conclusion, these findings provide evidence that the neuroprotection of KBA against oxidative stress-induced ischemic injury involves the Nrf2/HO-1 pathway.
Mol Neurobiol. 2015 Dec;52(3):1430-1439.
PMID: 25452227 [PubMed - indexed for MEDLINE]
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80. |
Neuroprotection by acetyl-11-keto-β-Boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway.
Ding Y, Chen M, Wang M, Wang M, Zhang T, Park J, Zhu Y, Guo C, Jia Y, Li Y, Wen A
Stroke is a complex disease involved oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway has been considered a potential target for neuroprotection in stroke. Acetyl-11-Keto-β-Boswellic Acid (AKBA) is an active triterpenoid compound from the extract of Boswellia serrate. The present study was to determine whether AKBA, a novel Nrf2 activator, can protect against cerebral ischemic injury. The stroke model was produced in Sprague-Dawley rats via middle cerebral artery occlusion. To model ischemia-like conditions in vitro, primary cultured cortical neurons were exposed to transient oxygen and glucose deprivation (OGD). Treatment of AKBA significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores by elevating the Nrf2 and HO-1 expression in brain tissues in middle cerebral artery occlusion (MCAO) rats at 48 hours post reperfusion. In primary cultured neurons, AKBA increased the Nrf2 and HO-1 expression, which provided protection against OGD-induced oxidative insult. Additionally, AKBA treatment increased Nrf2 binding activity to antioxidant-response elements (ARE). The protective effect of AKBA was attenuated by knockdown of Nrf2 or HO-1. In conclusion, these findings provide evidence that AKBA protects neurons against ischemic injury, and this neuroprotective effect involves the Nrf2/HO-1 pathway.
Sci Rep. 2014 Nov;4():7002.
PMID: 25384416 [PubMed - indexed for MEDLINE]
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81. |
Analgesic effects of crude extracts and fractions of Omani frankincense obtained from traditional medicinal plant Boswellia sacra on animal models.
Al-Harrasi A, Ali L, Hussain J, Rehman NU, Mehjabeen , Ahmed M, Al-Rawahi A
OBJECTIVE: To investigate the analgesic effect of Boswellia sacra (B. sacra), which could support the Omani traditional uses of frankincense for muscle, stomach, and arthritis pain.
METHODS: The crude extract, the essential oils and various sub-fractions of the crude methanol extract (each 300 mg/kg of the body weight of the animal) obtained from the resin of B. sacra were administered orally, and were evaluated for their analgesic activities by using two well known models of pain in mice, viz. acetic acid induced writhing test and formalin induced pain test in mice.
RESULTS: Of 13 samples, almost all of them were effective at an orally administered dose of 300 mg/kg of the body weight. The acetic acid induced writhes were inhibited in all the three phases with comparable values to the standard drug aspirin (300 mg/kg of body weight) with inhibition of 67.6% in phase I, 66.8% in phase II, and 37.9% in phase III. At the same time, all the tested samples were found effective in both the early and the late phases of formalin test. In formalin test, most of the tested samples showed more inhibitory effects as compared to the standard drug aspirin (300 mg/kg of body weight), which showed 36.2% and 29.6% inhibition in early and late phases respectively. Among the tested samples, the most significant inhibition was produced by Shabi frankincense oil (57.5% in early phase, and 55.6% in late phase). Interestingly, the extracts showed comparable percentage of inhibition to the oil and found in the following order: 60% chloroform/n-hexane sub-fraction (55.3% in early phase, and 66.7% in late phase), and 70% chloroform/n-hexane sub-fraction (59.6% in early phase, and 63.0% in late phase).
CONCLUSIONS: The present study provided the scientific justification about the analgesic properties of the essential oils, extract, and various sub-fractions obtained from the resin of B. sacra, thus validating its use in traditional folk medicines and other products; and hence supporting the development in the analgesic properties of bioactive natural substances.
Asian Pac J Trop Med. 2014 Sep;7S1():S485-90.
PMID: 25312172 [PubMed - as supplied by publisher]
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82. |
Identification of dehydroabietc acid from Boswellia thurifera resin as a positive GABAA receptor modulator.
Rueda DC, Raith M, De Mieri M, Schöffmann A, Hering S, Hamburger M
In a two-microelectrode voltage clamp assay with Xenopus laevis oocytes, a petroleum ether extract (100 μg/mL) of the resin of Boswellia thurifera (Burseraceae) potentiated GABA-induced chloride currents (IGABA) through receptors of the subtype α₁β₂γ₂s by 319.8% ± 79.8%. With the aid of HPLC-based activity profiling, three known terpenoids, dehydroabietic acid (1), incensole (2), and AKBA (3), were identified in the active fractions of the extract. Structure elucidation was achieved by means of HR-MS and microprobe 1D/2D NMR spectroscopy. Compound 1 induced significant receptor modulation in the oocyte assay, with a maximal potentiation of IGABA of 397.5% ± 34.0%, and EC₅₀ of 8.7 μM ± 1.3 μM. This is the first report of dehydroabietic acid as a positive GABAA receptor modulator.
Fitoterapia. 2014 Dec;99():28-34.
PMID: 25200370 [PubMed - indexed for MEDLINE]
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83. |
The therapeutic effect of the aqueous extract of boswellia serrata on the learning deficit in kindled rats.
Jalili C, Salahshoor MR, Moradi S, Pourmotabbed A, Motaghi M
BACKGROUND: It has been reported that epilepsy is a disorder of the central nervous system that causes memory impairment. This study examines the role of the aqueous extract of Boswellia on the learning disability of the pentylenetetrazol (PTZ)-induced kindled rats.
METHODS: In this experimental study, 64 male rats were used. Kindling seizures were induced by three injections of 25 mg/kg of PTZ every 15 min. Control animals received normal saline instead. To evaluate the therapeutic effect of Boswellia extract on the PTZ-induced cognitive deficits, the aqueous extract (0, 0.1, 0.5 or 1 g/kg, i.p.) were administrated to all animals for three consecutive days. At 24 h later, passive avoidance learning of animals was examined using shuttle box apparatus, respectively. The time required for the animal stepping through the dark chamber was determined as step-through latency (STL). Data were subjected to the t-test and analysis of variance and followed by Tukey's test for multiple comparisons.
RESULTS: The STL of the kindled rats was significantly reduced compared with control ones (22/375 ± 4/19 for kindled and 295 ± 15/71 for control groups, respectively). Aqueous extract of Boswellia improved passive-avoidance learning ability in both control and PTZ-kindled animals (P < 0.05).
CONCLUSIONS: The results can be stated that the Boswellia extract is offset by harmful effects of seizures on cognitive function and consumption of Boswellia extract increases the learning ability in epileptic animals.
Int J Prev Med. 2014 May;5(5):563-8.
PMID: 24932387 [PubMed - as supplied by publisher]
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84. |
Effect of Boswellia serrata gum resin on the morphology of hippocampal CA1 pyramidal cells in aged rat.
Hosseini-sharifabad M, Esfandiari E
Experimental evidence indicates that administration of Boswellia resin, known as olibanum or Frankincense, increases memory power. It is reported that beta boswellic acid, the major component of Boswellia serrata gum resin, could enhance neurite outgrowth and branching in hippocampal neurons. We therefore studied whether Boswellia treatment produces morphological changes in the superior region of cornu ammonis (CA1) in aged rats. Sixteen male Wistar rats, 24 months of age, were randomly divided in experimental and control groups. The experimental group was orally administered Boswellia serrata gum resin (100 mg/kg per day for 8 weeks) and the control group received a similar volume of water. The Cavalieri principle was employed to estimate the volumes of CA1 hippocampal field, and a quantitative Golgi study was used to analysis of dendritic arborizations of CA1 pyramidal cells. Comparisons revealed that Boswellia-treated aged rats had greater volumes than control animals in stratum pyramidale and stratum radiatum lacunosum-moleculare. The neurons of CA1 in experimental rats had more dendritic segments (40.25 ± 4.20) than controls (30.9 ± 4.55), P = 0.001. The total dendritic length of CA1 neurons was approximately 20 % larger in the experimental group compared to control. Results also indicated that the aged rats treated with Boswellia resin had more numerical branching density in the apical dendrites of CA1 pyramidal neurons. The results of the present study show that long-term administration of Boswellia resin can attenuate age-related dendritic regression in CA1 pyramidal cells in rat hippocampus.
Anat Sci Int. 2015 Jan;90(1):47-53.
PMID: 24515442 [PubMed - indexed for MEDLINE]
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85. |
An in vitro study of the role of β-boswellic acid in the microtubule assembly dynamics.
Karima O, Riazi G, Khodadadi S, Yousefi R, Mahnam K, Mokhtari F, Cheraghi T, Hoveizi E, Moosavi-Movahedi AA
Structural integrity of microtubule protein (MTP) is pivotal for its physiological roles. Disruption of the MTP network is known to be involved in neurodegenerative disorders. The gum resin of plants of the boswellia species, with β-boswellic acid (BBA) as the major component, has long been used in Ayurveda and Oriental Medicine to prevent amnesia. In the current study, we addressed the question whether BBA affects assembly dynamics behavior of tubulin. Our in vitro results revealed that BBA increases MTP length distribution and the polymerization rate of tubulin, moderately stabilizing it and diminishing both the critical concentration (C(c)) and the fraction of inactive tubulin (F(i)).
FEBS Lett. 2012 Nov;586(23):4132-8.
PMID: 23098754 [PubMed - indexed for MEDLINE]
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86. |
Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals.
Moussaieff A, Gross M, Nesher E, Tikhonov T, Yadid G, Pinhasov A
Incensole acetate (IA), a constituent of Boswellia resin ('frankincense'), was previously demonstrated to exhibit an antidepressive-like effect in the Forced Swim Test (FST) in mice following single dose administration (50 mg/kg). Here, we show that acute administration of considerably lower dose (10 mg/kg) IA to selectively bred mice, showing prominent submissive behavior, exerted significant antidepressant-like effects in the FST. Furthermore, chronic administration of 1 or 5 mg/kg per day of IA for three consecutive weeks dose- and time-dependently reduced the submissiveness of the mice in the Dominant-Submissive Relationship test, developed to screen the chronic effect of antidepressants. This behavioral effect was concomitant to reduced serum corticosterone levels, dose-dependent down-regulation of corticotropin releasing factor and up-regulation of brain derived neurotrophic factor transcripts IV and VI expression in the hippocampus. These data suggest that IA modulates the hypothalamic-pituitary-adrenal (HPA) axis and influences hippocampal gene expression, leading to beneficial behavioral effects supporting its potential as a novel treatment of depressive-like disorders.
J Psychopharmacol. 2012 Dec;26(12):1584-93.
PMID: 23015543 [PubMed - indexed for MEDLINE]
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87. |
The synergistic effect of beta-boswellic acid and Nurr1 overexpression on dopaminergic programming of antioxidant glutathione peroxidase-1-expressing murine embryonic stem cells.
Abasi M, Massumi M, Riazi G, Amini H
Parkinson's disease (PD) is a neurodegenerative disorder in which the nigro-striatal dopaminergic (DAergic) neurons have been selectively lost. Due to side effects of levodopa, a dopamine precursor drug, recently cell replacement therapy for PD has been considered. Lack of sufficient amounts of, embryos and ethical problems regarding the use of dopamine-rich embryonic neural cells have limited the application of these cells for PD cell therapy. Therefore, many investigators have focused on using the pluripotent stem cells to generate DAergic neurons. This study is aimed first to establish a mouse embryonic stem (mES) cell line that can stably co-express Nurr1 (Nuclear receptor subfamily 4, group A, member 2) transcription factor in order to efficiently generate DAergic neurons, and glutathione peroxidase-1 (GPX-1) to protect the differentiated DAergic-like cells against oxidative stress. In addition to genetic engineering of ES cells, the effect of Beta-boswellic acid (BBA) on DAergic differentiation course of mES cells was sought in the present study. To that end, the feeder-independent CGR8 mouse embryonic stem cells were transduced by Nurr1- and GPX-1-harboring Lentiviruses and the generated Nurr1/GPX-1-expresssing ES clones were characterized and verified. Gene expression analyses demonstrated that BBA treatment and overexpression of Nurr1 has a synergistic effect on derivation of DAergic neurons from Nurr1/GPX-1-expressing ES cells. The differentiated cells could exclusively synthesize and secrete dopamine in response to stimuli. Overexpression of GPX-1 in genetically engineered Nurr1/GPX-1-ES cells increased the viability of these cells during their differentiation into CNS stem cells. In conclusion, the results demonstrated that Nurr1-overexpressing feeder-independent ES cells like the feeder-dependent ES cells, can be efficiently programmed into functional DAergic neurons and additional treatment of cells by BBA can even augment this efficiency. GPX-1 overexpression in Nurr1/GPX-1-ES cells increases the viability of differentiated CNS stem-like cells. The result of this study may have impact on future stem cell therapy of PD.
Neuroscience. 2012 Oct;222():404-16.
PMID: 22800564 [PubMed - indexed for MEDLINE]
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88. |
Protective effects of incensole acetate on cerebral ischemic injury.
Moussaieff A, Yu J, Zhu H, Gattoni-Celli S, Shohami E, Kindy MS
The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-κB activation and concomitant inflammation, as well as the neurological deficit following head trauma. Here, we show that IA protects against ischemic neuronal damage and reperfusion injury in mice, attenuating the inflammatory nature of ischemic damage. IA given post-ischemia, reduced infarct volumes and improved neurological activities in the mouse model of ischemic injury in a dose dependent fashion. The protection from damage was accompanied by inhibition of TNF-α, IL-1β and TGF-β expression, as well as NF-κB activation following injury. In addition, IA is shown to have a therapeutic window of treatment up to 6h after ischemic injury. Finally, the protective effects of IA were partially mediated by TRPV3 channels as determined by the TRPV3 deficient mice and channel blocker studies. This study suggests that the anti-inflammatory and neuroprotective activities of IA may serve as a novel therapeutic treatment for ischemic and reperfusion injury, and as a tool in the ongoing research of mechanisms for neurological damage.
Brain Res. 2012 Mar;1443():89-97.
PMID: 22284622 [PubMed - indexed for MEDLINE]
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89. |
The effects of olibanum administered to methimazole-treated dams during lactation on learning and memory of offspring rats.
Hosseini M, Shafei MN, Safari V, Taiarani Z, Kafami Ladani M, Sadeghian R
The effect of olibanum administered during lactation to methimazole-treated dams on the learning of offspring was evaluated. The animals were treated for 60 days from the first day of lactation period: group 1--tap water, group 2-0.03% methimazole and groups 3 and 4-0.03% methimazole with 0.25% or 0.125% olibanum, respectively. The serum thyroxin level in the offspring of group 2 was significantly lower than that of group 1. However, there was no difference compared to groups 3 and 4. In a Morris water maze, the distance and time latency to reach the platform in offspring of group 2 was significantly higher than groups 1, 3 and 4. In probe trial, the time spent in target quadrant (Q₁) by offspring of group 2 was lower than groups 1, 3 and 4. It is suggested that impaired learning and memory in the offspring of hypothyroid rats may be prevented by olibanum.
Nat Prod Res. 2012;26(16):1544-8.
PMID: 22007658 [PubMed - indexed for MEDLINE]
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90. |
Evaluation of systemic administration of Boswellia papyrifera extracts on spatial memory retention in male rats.
Mahmoudi A, Hosseini-Sharifabad A, Monsef-Esfahani HR, Yazdinejad AR, Khanavi M, Roghani A, Beyer C, Sharifzadeh M
Time-dependent effects of ethanolic extract of Boswellia papyrifera, administered systemically, on spatial memory retention in the Morris water maze were investigated in male rats. A total extract of Boswellia papyrifera (300 mg/kg) was administered every eight hours to three groups of rats by gavage for 1, 2 and 4 weeks. In a separate set of experiments, three doses of a fraction of the extract, called the boswellic acids (100, 200 and 300 mg/kg) were administered by gavage to three groups of rats three times a day for 2 weeks. Following these applications, animals were trained for 4 days. Behavioral testing for evaluation of spatial memory retention was performed 48 h after completion of training. Boswellia papyrifera extracts and boswellic acids caused a significant reduction in escape latency and distance traveled but had no influence on swimming speed. These findings provide evidence that Boswellia papyrifera extracts affect spatial memory retention irrespective of the treatment period. In addition our data show that systemic administration of the boswellic acids fraction enhanced spatial memory retention in a dose-dependent manner. These improving effects may be due to some extent to the interactions of these products with inflammatory mediators, neurotransmitter signaling cascades or protein kinase pathways in the brain.
J Nat Med. 2011 Jul;65(3-4):519-25.
PMID: 21479965 [PubMed - indexed for MEDLINE]
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91. |
Anticholinesterase activity of endemic plant extracts from Soqotra.
Bakthira H, Awadh Ali NA, Arnold N, Teichert A, Wessjohann L
A total of 30 chloroform and methanol extracts from the following endemic Soqotran plants Acridocarpus socotranus Olive, Boswellia socotranao Balf.fil, Boswellia elongata Balf. fil., Caralluma socotrana N. Br, Cephalocroton socotranus Balf.f, Croton socotranus Balf. fil.., Dendrosicycos socotrana Balf.f., Dorstenia gigas Schweinf. ex Balf. fil., Eureiandra balfourii Cogn. & Balf. fil., Kalanchoe farinaceae Balf.f, Limonium sokotranum (Vierh) Radcl. Sm), Oldenlandia pulvinata, Pulicaria diversifolia (Balf. and Pulicaria stephanocarpa Balf. were screened for their acetylcholinesterase inhibitory activity by using in vitro Ellman method at 50 and 200 µg/ml concentrations. Chloroform extracts of Croton socotranus, Boswellia socotrana, Dorstenia gigas, and Pulicaria stephanocarpa as well as methanol extracts of Eureiandra balfourii exhibited inhibitory activities higher than 50 % at concentration of 200 µg. At a concentrations of 50 µg, the chloroform extract of Croton socotranus exhibited an inhibition of 40.6 %.
Afr J Tradit Complement Altern Med. 2011;8(3):296-9.
PMID: 22468008 [PubMed - indexed for MEDLINE]
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92. |
The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze.
Hosseini M, Hadjzadeh MA, Derakhshan M, Havakhah S, Rassouli FB, Rakhshandeh H, Saffarzadeh F
Functional consequences of hypothyroidism include impaired learning and memory and inability to produce long-term potentiation (LTP) in hippocampus. Olibanum has been used for variety of therapeutic purposes. In traditional medicine, oilbanum is used to enhance learning and memory. In the present study the effect of olibanum on memory deficit in hypothyroid rats was investigated. Male wistar rats were divided into four groups and treated for 180 days. Group 1 received tap drinking water while in group 2, 0.03% methimazol was added to drinking water. Group 3 and 4 were treated with 0.03% methimazole as well as 100 and 500 mg/kg olibanum respectively. The animals were tested in Morris water maze. The swimming speed was significantly lower and the distance and time latency were higher in group 2 compared with group 1. In groups 3 and 4 the swimming speed was significantly higher while, the length of the swim path and time latency were significantly lower in comparison with group 2. It is concluded that methimazole-induced hypothyroidism impairs learning and memory in adult rats which could be prevented by using olibanum.
Arch Pharm Res. 2010 Mar;33(3):463-8.
PMID: 20361313 [PubMed - indexed for MEDLINE]
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93. |
The enhancement effect of beta-boswellic acid on hippocampal neurites outgrowth and branching (an in vitro study).
Karima O, Riazi G, Yousefi R, Movahedi AA
Increasing evidences implicate impairment of axonal integrity in mechanisms underlying neurodegenerative disorders. Beta-boswellic acid (BBA) is the major component of Boswellia serrata gum. This resin has long been used in Ayurveda (India's traditional medicine) to prevent amnesia. In this study, the effect of BBA was examined on neurites outgrowth and branching as well as on polymerization dynamics of tubulin. The morphometric parameters (axonal length and neuritis branching) were examined microscopically after treating the hippocampal cells with BBA. Also the assembly process of tubulin was assessed using UV/V is spectrophotometer through following of absorbance at 350 nm. The results revealed that BBA could significantly enhance neurite outgrowth, branching, and tubulin polymerization dynamics. The obtained results suggest that enhancing effect of BBA on microtubule polymerization kinetics might be the origin of increasing axonal outgrowth and branching.
Neurol Sci. 2010 Jun;31(3):315-20.
PMID: 20217445 [PubMed - indexed for MEDLINE]
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94. |
Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain.
Moussaieff A, Rimmerman N, Bregman T, Straiker A, Felder CC, Shoham S, Kashman Y, Huang SM, Lee H, Shohami E, Mackie K, Caterina MJ, Walker JM, Fride E, Mechoulam R
Burning of Boswellia resin as incense has been part of religious and cultural ceremonies for millennia and is believed to contribute to the spiritual exaltation associated with such events. Transient receptor potential vanilloid (TRPV) 3 is an ion channel implicated in the perception of warmth in the skin. TRPV3 mRNA has also been found in neurons throughout the brain; however, the role of TRPV3 channels there remains unknown. Here we show that incensole acetate (IA), a Boswellia resin constituent, is a potent TRPV3 agonist that causes anxiolytic-like and antidepressive-like behavioral effects in wild-type (WT) mice with concomitant changes in c-Fos activation in the brain. These behavioral effects were not noted in TRPV3(-/-) mice, suggesting that they are mediated via TRPV3 channels. IA activated TRPV3 channels stably expressed in HEK293 cells and in keratinocytes from TRPV3(+/+) mice. It had no effect on keratinocytes from TRPV3(-/-) mice and showed modest or no effect on TRPV1, TRPV2, and TRPV4, as well as on 24 other receptors, ion channels, and transport proteins. Our results imply that TRPV3 channels in the brain may play a role in emotional regulation. Furthermore, the biochemical and pharmacological effects of IA may provide a biological basis for deeply rooted cultural and religious traditions.
FASEB J. 2008 Aug;22(8):3024-34.
PMID: 18492727 [PubMed - indexed for MEDLINE]
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95. |
Incensole acetate: a novel neuroprotective agent isolated from Boswellia carterii.
Moussaieff A, Shein NA, Tsenter J, Grigoriadis S, Simeonidou C, Alexandrovich AG, Trembovler V, Ben-Neriah Y, Schmitz ML, Fiebich BL, Munoz E, Mechoulam R, Shohami E
Boswellia resin has been used as a major anti-inflammatory agent and for the healing of wounds for centuries. Incensole acetate (IA), isolated from this resin, was shown to inhibit the activation of nuclear factor-kappaB, a key transcription factor in the inflammatory response. We now show that IA inhibits the production of inflammatory mediators in an in vitro model system of C6 glioma and human peripheral monocytes. Given the involvement of postinjury inflammation in the pathophysiology and outcome of traumatic brain injury, we examined the effect of IA on the inflammatory process and on the recovery of neurobehavioral and cognitive functions in a mouse model of closed head injury (CHI). In the brains of post-CHI mice, IA reduced glial activation, inhibited the expression of interleukin-1beta, and tumor necrosis factor-alpha mRNAs, and induced cell death in macrophages at the area of trauma. A mild hypothermic effect was also noted. Subsequently, IA inhibited hippocampal neurodegeneration and exerted a beneficial effect on functional outcome after CHI, indicated by reduced neurological severity scores and improved cognitive ability in an object recognition test. This study attributes the anti-inflammatory activity of Boswellia resin to IA and related cembranoid diterpenes and suggests that they may serve as novel neuroprotective agents.
J Cereb Blood Flow Metab. 2008 Jul;28(7):1341-52.
PMID: 18414499 [PubMed - indexed for MEDLINE]
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96. |
Co-administration of acetyl-11-keto-beta-boswellic acid, a specific 5-lipoxygenase inhibitor, potentiates the protective effect of COX-2 inhibitors in kainic acid-induced neurotoxicity in mice.
Bishnoi M, Patil CS, Kumar A, Kulkarni SK
Cyclooxygenase (COX) and lipoxygenase (LOX) are responsible for the metabolism of arachidonic acid into inflammatory metabolites, prostaglandins and leukotrienes, respectively. The upregulation of these enzymes in the central nervous system has been demonstrated to be responsible for the increased neuronal vulnerability to degeneration. Kainic acid, a glutamate receptor agonist and responsible for neuronal excitotoxicity and oxidative damage via different mechanisms, is capable of stimulating mRNA of both COX-2 and 5-LOX in the brain. The present study was designed to study the effects of COX inhibitors (indomethacin, nimesulide, rofecoxib) and a 5-LOX inhibitor (acetyl-11-keto-beta-boswellic acid; AKBA) and the combination of these inhibitors (dual inhibition) on kainic acid induced excitotoxicity and oxidative and nitrosative damage in mice. The results from the present study indicated that AKBA, indomethacin, and nimesulide per se did not produce any change in the behavioural parameters after kainic acid administration; however, rofecoxib per seproduced a significant increase in the latency of clonic (seizure-like) movement and a decrease in mortality rate as compared with kainic acid treated animals. In combination studies AKBA, rofecoxib, and nimesulide produced a more pronounced effect than either of these drugs alone. Further, the effect of AKBA combined with rofecoxib was significantly more marked when compared with AKBA combined with nimesulide. Besides this, identical results were found for the effect of these agents and their combination against oxidative damage induced by kainic acid. These findings indicate the potential role of COX-2 inhibitors and also their combination with the 5-LOX inhibitor in kainic acid induced excitotoxicity and oxidative damage by virtue of their antioxidant effect and suggest the need for the development of dual inhibitors for the treatment of neuronal excitotoxicity.
Pharmacology. 2007;79(1):34-41.
PMID: 17139192 [PubMed - indexed for MEDLINE]
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97. |
Potentiation of antinociceptive effect of NSAIDs by a specific lipooxygenase inhibitor, acetyl 11-keto-beta boswellic acid.
Bishnoi M, Patil CS, Kumar A, Kulkarni SK
The present study was aimed to assess the combined effects of cyclooxygenase and 5-lipoxygenase (COX/5-LOX) inhibitors in different animal models of nociception. Naproxen, nimesulide and rofecoxib are well-established antinociceptive agents acting via COX inhibition. AKBA (acetyl-keto-beta-boswellic acid) is a 5-LOX inhibitor. AKBA (50-200 mg/kg) produced a dose dependent and significant antinociceptive effect in different animal models of nociception. Based on the earlier reports from our laboratory, sub effective doses of all the three COX Inhibitors were selected and they were administered (naproxen, 5 mg/kg; nimesulide, 1 mg/kg; and rofecoxib, 1 mg/kg) with AKBA (100 mg/kg). This produced a more significant antinociceptive effect as compared to per se effect observed in all the three models of nociception. However, the effect of combination of nimesulide with AKBA was more pronounced as compared to naproxen and rofecoxib and their combination with AKBA. The present finding provided an evidence for the potentiation of antinociceptive effect of NSAIDs with AKBA. Such a combination may help to reduce the therapeutic doses of conventional NSAIDs and also reduce side effects (gastric, cardiac and renal) that are popularly associated with the NSAIDs.
Indian J Exp Biol. 2006 Feb;44(2):128-32.
PMID: 16480179 [PubMed - indexed for MEDLINE]
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98. |
Protective effects of nimesulide (COX Inhibitor), AKBA (5-LOX Inhibitor), and their combination in aging-associated abnormalities in mice.
Bishnoi M, Patil CS, Kumar A, Kulkarni SK
Several inflammatory processes play a critical role in brain aging and are associated with increased vulnerability to neurodegeneration. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two enzymes involved in the oxygenation of the arachidonic acid, are upregulated in the central nervous system during aging and are associated with different aging-related brain pathologies. The present experiment was performed to study the effects of 5-LOX inhibitor, acetyl-11-keto-beta-boswellic acid (AKBA), nimesulide (preferential COX-2 inhibitor), and their combination on cognitive performance of young and aged mice, using elevated plus maze test. Chronic administration of AKBA (100 mg/kg, p.o.) and nimesulide (2.42 mg/kg, p.o.) for 15 days significantly reversed the aging-induced retention deficit in mice. Coadministration of AKBA and nimesulide enhanced the cognitive performance in aged mice when compared with that in per se treatment. The aging-related increase in oxidative damage (increased LPO and decreased GSH) was reversed by AKBA, nimesulide, and their combination. Further, per se COX and LOX inhibitors and their combination did not produce any alteration in gastrointestinal parameters; they also reversed the aging-induced motor dysfunction in the aged animals. On the basis of these observations, present findings indicated that the combination of COX and LOX inhibitors (dual inhibitors) may provide a new therapeutic innovation for the treatment of aging-related brain disorders such as Alzheimer's disease and different motor dysfunctions with adequate gastrointestinal tolerability.
Methods Find Exp Clin Pharmacol. 2005 Sep;27(7):465-70.
PMID: 16258590 [PubMed - indexed for MEDLINE]
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99. |
Analgesic and psychopharmacological effects of the gum resin of Boswellia serrata.
Menon MK, Kar A
Planta Med. 1971 Apr;19(4):333-41.
PMID: 5573545 [PubMed - indexed for MEDLINE]
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100. |
Analgesic effect of the gum resin of Boswellia serata Roxb.
Kar A, Menon MK
Life Sci. 1969 Oct;8(19):1023-8.
PMID: 5351016 [PubMed - indexed for MEDLINE]
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