| 1. |
Extracts Ameliorates Symptom of Irregularities in Articular Cartilage through Inhibition of Matrix Metalloproteinases Activation and Apoptosis in Monosodium-Iodoacetate-Induced Osteoarthritic Rat Models.
Kim J, Eun S, Jung H, Kim J, Kim J
The research examined the effects of extracts (BSE) on a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). The severity and progression of MIA-induced osteoarthritis were assessed using microcomputed tomography imaging. Additionally, the study investigated the impact of BSE various the biomarkers associated with osteoarthritis, including anabolic and catabolic factors, pro-inflammatory factors, and apoptosis factors. The evaluation methods employed included western blot, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction analysis in osteoarthritic rats. Supplementing osteoarthritic rats with BSE reduced tissue injury, cartilage destruction, and decreased in MIA-induced roughness on the articular cartilage surface. MIA-treated rats exhibited increased expressions of phosphorylation of Smad3, MMPs, p-IκB, p-NF-κB, and pro-inflammatory factors (IL-1β, IL-6, TNF-α, and COX-2), which were mitigated by BSE supplementation. Furthermore, protein expressions related to apoptosis pathways were significantly reduced in MIA-induced rats supplemented with BSE. These findings suggested that BSE ingestion may enhance the inflammatory response, decrease JNK-dependent MMPs activation, and alleviate caspase-3-dependent apoptosis in MIA-induced osteoarthritic rat models. Consequently, BSE exhibits potential as a therapeutic agent for treating osteoarthritis.
Prev Nutr Food Sci. 2023 Sep;28(3):285-292.
PMID: 37842260 [PubMed - as supplied by publisher]
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| 2. |
Anti-inflammatory and anti-arthritic potential of methotrexate in combination with BA-25, an amino analogue of β-boswellic acid in the treatment of rheumatoid arthritis.
Choudhary R, Saroch D, Kumar D, Anjum S, Andrabi NI, Akram T, Shah BA, Shukla SK, Bhagat A, Kour G, Ahmed Z
β- boswellic acid, a pentacyclic triterpene derived from Boswellia serrata is extensively known for its anti-inflammatory potential. BA-25 (3-α-o-acetoxy-4β-amino-11-oxo-24-norurs-12-ene) is an amino analogue of β-boswellic acid that has shown anti-inflammatory potential in LPS-induced macrophages and animal models. The present study aims at investigation of the combination of BA-25 with the conventional gold standard DMARD methotrexate (MTX) for its anti-inflammatory and anti-arthritic potential using in vitro and in vivo experimental models. The anti-inflammatory potential of MTX versus the combination (BA-25 + MTX) was investigated for inhibition of NO, ROS and pro-inflammatory cytokines including TNF-α and IL-6 using ELISA in LPS-stimulated RAW-264.7 cells. The results demonstrated significant reduction in NO, ROS, TNF- α and IL-6 production with the combination treatment in comparison to MTX alone. The cytokine inhibition potential of the combination was further validated in-vivo using balb/c wherein the combination restored LPS-induced increase in pro-inflammatory cytokines. The toxicological aspect of the in vivo doses of the combination was also investigated in mice after dosing for 28 days wherein the results suggested no significant change in the hematological parameters and serum biochemical parameters in the combination versus the vehicle group. The effect of BA-25 was also investigated on MTX-induced increase in liver function tests and the expression of Bax and blc2. The results demonstrated decrease in the production of liver enzymes with BA-25 administration along with downregulating the expression of apoptotic protein Bax while increasing the expression of anti-apoptotic protein Bcl2. Furthermore, pharmacokinetic studies of BA-25 were conducted in Balb/c mice wherein the compound showed rapid absorption, high volume of distribution and a t of 13.08. Finally the anti-arthritic effect of the combination of MTX + BA-25 vs MTX alone was investigated using CIA model in DBA/1 mice wherein the treatment with the combination resulted in significant reduction in paw inflammation, IL-6 and IL-1β levels. Furthermore, the western blot analysis demonstrated considerable decrease in the expression of p-NF-κB p and p-IκB in the ankle-joint tissue of the CIA mice treated with the combination therapy. The results insinuated increased anti-inflammatory and anti-arthritic potential of the combination of MTX with BA-25 as evident from in to vitro and in-vivo studies.
Cytokine. 2023 Dec;172():156398.
PMID: 37820446 [PubMed - indexed for MEDLINE]
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| 3. |
Insights into the anti-inflammatory and anti-arthritic potential of 3-Acetyl-11-keto-β-Boswellic Acid as a therapeutic approach in Rheumatoid Arthritis.
Priya S, Singhvi G
Expert Opin Investig Drugs. 2023;32(10):867-871.
PMID: 37817458 [PubMed - indexed for MEDLINE]
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| 4. |
Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA.
Hussain N, Mumtaz M, Adil M, Ali Nadeem A, Sarwar A, Aziz T, Alharbi M, Alshammari A, Alasmari AF, Alharbi ME
Mutation in the VEGF gene disturbs the production of chondrocytes and angiogenesis which are essential for cartilage health. Cytokines and chemokines produced by auto-activation of B-cells degrade cartilage. Bruton's Tyrosine Kinase (BTK) plays a crucial role in the activation of these B-cells. VEGF has a central part in angiogenesis, in the recruitment of endothelial cells, and is involved in mechanisms that result in tumour formation. The objective of this research is to investigate the potential role of VEGF polymorphism in the development of Rheumatoid Arthritis (RA) and the screening of potential natural, synthetic BTK inhibitor compounds as possible in-silico chemotherapeutic agents to control auto-activation of B-cells and cartilage degrading cytokines. In this study, it had been shown that allele A frequency was significantly higher than that of allele C in RA-positive patients as compared to controls. Hence it depicts that allele A of VEGF (rs699947) can increase the risk of RA while allele C has a protective role. The phytochemicals which showed maximum binding affinity at the inhibitory site of BTK include beta boswellic acid, tanshinone, and baicalin. These phytochemicals as BTK inhibitor give insights to use them as anti-arthritic compounds by nanoparticle drug delivery mechanism.
Acta Biochim Pol. 2023 Sep;70(3):591-598.
PMID: 37669474 [PubMed - indexed for MEDLINE]
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| 5. |
Management of Osteoarthritis and Joint Support Using Feed Supplements: A Scoping Review of Undenatured Type II Collagen and .
Zapata A, Fernández-Parra R
In the multimodal management of osteoarthritis (OA) in recent decades, the use of feed supplements to maintain joint cartilage has been advocated. The aim of this scoping review is to present the results found in the veterinary literature on the use of undenatured type II collagen and in dogs, specifically its use in dogs with clinical signs of OA, healthy dogs after intense exercise or dogs with diseases that predispose the individual to OA. For this purpose, a literature review was carried out using the electronic databases PubMed, Web of Science and Google Scholar, from which a total of 26 records were included in this review: fourteen evaluating undenatured type II collagen, ten evaluating and two evaluating the combination of undenatured type II collagen and . The review of the records showed that undenatured type II collagen decreases the clinical signs associated with OA, improving the general clinical state with a reduction in the degree of lameness and increase in physical activity or mobility. Evaluating the response to supplementation with alone is complicated due to the limited publication of studies and variations in the purity and compositions of the products used, but in general terms, its combination with other feed supplements produces benefits by relieving pain and reducing the clinical signs of OA in dogs. The combination of both in the same product provides results similar to those obtained in undenatured type II collagen studies. In conclusion, undenatured type II collagen and are considered a valid option for the multimodal approach to the management of OA and for improving activity during intense exercise, but more studies are needed to conclude whether or not it prevents OA in dogs.
Animals (Basel). 2023 Feb;13(5):.
PMID: 36899726 [PubMed - as supplied by publisher]
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| 6. |
Effects of Extract Alone and Combined with Extract on Monosodium Iodoacetate Model of Osteoarthritis in Mice.
Khoramjouy M, Bayanati M, Noori S, Faizi M, Zarghi A
BACKGROUND: As a chronic joint condition, osteoarthritis (OA) is a common problem among older people. Pain, aching, stiffness, swelling, decreased flexibility, reduced function, and disability are the symptoms of arthritis.
OBJECTIVES: In this study, we tested the extracts of (ZJE) and (BSE) to reduce OA symptoms as an alternative treatment.
METHODS: NMRI mice were administered an intra-articular injection of monosodium iodoacetate (MIA; 1 mg/10 mL) in the left knee joint cavity for the induction of OA. Hydroalcoholic extracts of ZJE (250 and 500 mg/kg), BSE (100 and 200 mg/kg), and combined ZJE and BSE were orally administered daily for 21 days. Following behavioral tests, plasma samples were collected to detect inflammatory factors. To screen for general toxicity, acute oral toxicity was evaluated.
RESULTS: Oral administration of all the hydroalcoholic extracts significantly increased the locomotor activity, pixel values of the foot-print area, paw withdrawal threshold, the latency of the withdrawal response to heat stimulation, and decreased the difference between pixel values of hind limbs compared to the vehicle group. Also, the elevated levels of IL-1β, IL-6, and TNF-α were reduced. As tested in this study, ZJE and BSE were practically nontoxic and had a high degree of safety.
CONCLUSIONS: This study demonstrated that the oral administration of ZJE and BSE slows the progression of OA through anti-nociceptive and anti-inflammatory properties. Oral co-administration of ZJE and BSE extracts can be used as herbal medicine to inhibit OA progression.
Iran J Pharm Res. 2022 Dec;21(1):e134338.
PMID: 36896317 [PubMed - as supplied by publisher]
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| 7. |
Fast pain relief in exercise-induced acute musculoskeletal pain by turmeric-boswellia formulation: A randomized placebo-controlled double-blinded multicentre study.
Rudrappa GH, Murthy M, Saklecha S, Kumar Kare S, Gupta A, Basu I
BACKGROUND: Plant extracts with analgesic properties are seldom considered for treatment of acute musculoskeletal pain due to delay in onset of analgesia. Turmeric (Curcuma longa) and boswellia (Boswellia serrata) extracts are well-studied anti-inflammatory compounds gaining in popularity and used as an alternative to conventional treatments for musculoskeletal pain. This study analyzed the analgesic effect of a formulation of turmeric and boswellia extracts in sesame oil (Rhuleave-K, TBF) in reducing exercise-induced acute musculoskeletal pain in healthy participants.
METHODS: In this randomized double-blinded placebo-controlled, single-dose, single-day, multicentre study, a total of 232 participants (TBF n = 116; placebo n = 116) having moderate-to-severe exercise-induced acute musculoskeletal pain were randomized in an allocation concealed 1:1 ratio to receive a single dose of 1000 mg of TBF or placebo. The outcome measures were numerical rating scale (NRS), categorical pain relief scale (PRS), onset of analgesia, and short form of McGill questionnaire (SF-MPQ). NRS and PRS were measured from predose to every 30 minutes interval of postdose up to 6 hours at rest, with movement and applying pressure on the affected part. The onset of analgesia was measured from the time of dosage and censored at 6 hours of postdose. The sum of pain intensity difference (SPID6) and total pain relief (TOTPAR6) at 6 hours was, respectively, analyzed from NRS and PRS scores.
RESULTS: TBF showed a significant reduction in pain intensity (SPID6rest) with 97.85% improvement in cumulative responder analysis compared with 2.46% in placebo. The onset of pain relief was fast and highly significant in the TBF group with 99% of participants having a mean perceptible pain relief at 68.5 minutes (95% confidence interval, 59.5-77.4) and 96% of participants having a mean meaningful pain relief at 191.6 minutes (95% confidence interval, 176.7-206.4) compared to the placebo group. Highly significant and continuous improvement in pain relief was observed in the TBF group with 93% of participants having ≥ 50% of maximum TOTPAR6 with a number needed to treat of 1.1 at rest.
CONCLUSION: Exercise-induced acute musculoskeletal pain can be effectively relieved by TBF (Rhuleave-K) in about 3 hours signifying its strong analgesic activity.
Medicine (Baltimore). 2022 Sep;101(35):e30144.
PMID: 36107505 [PubMed - indexed for MEDLINE]
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| 8. |
β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways.
Park GD, Cheon YH, Eun SY, Lee CH, Lee MS, Kim JY, Cho HJ
Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. β-boswellic acid (βBA) is a natural compound found in , which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of βBA on osteoclastogenesis. βBA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, βBA significantly inhibited the phosphorylation of IκB, Btk, and PLCγ2 and the degradation of IκB. Additionally, βBA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as and . These results suggest that βBA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis.
Molecules. 2021 May;26(9):.
PMID: 34062884 [PubMed - indexed for MEDLINE]
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| 9. |
Inhibitory effect of acetyl-11-keto-β-boswellic acid on titanium particle-induced bone loss by abrogating osteoclast formation and downregulating the ERK signaling pathway.
Shi J, Gu Y, Wang Y, Bai J, Xiong L, Tao Y, Xue Y, Xu Y, Yang H, Ye H, Geng D
Wear debris-induced osteoclast accumulation around implants plays a crucial role during the progression of periprosthetic osteolysis (PPO). We have confirmed that acetyl-11-keto-β-boswellic acid (AKBA) promotes bone formation and protects against particle-induced bone destruction in vivo. However, the effect of AKBA on titanium-induced bone resorption is unknown. In this study, we detected the inhibitory effect of AKBA on titanium-induced bone erosion in vivo and used RAW264.7 cells and bone marrow macrophages (BMMs) to investigate the effect and underlying mechanism of AKBA on the differentiation and resorptive function of osteoclasts. Our findings revealed that AKBA inhibited particle-induced bone loss and osteoclast formation in vivo. Furthermore, AKBA exerted inhibitory effects on RANKL-induced osteoclastogenesis, osteoclastic ring-dependent resorption and the expression of osteoclast marker genes via the ERK signaling pathway in vitro. Our data further established the protective effect of AKBA on titanium particle-induced bone erosion from a new perspective of bone erosion prevention, strongly confirming that AKBA is an appropriate agent for protection against PPO.
Int Immunopharmacol. 2021 May;94():107459.
PMID: 33611061 [PubMed - indexed for MEDLINE]
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| 10. |
The Beneficial Effect of Boswellic Acid on Bone Metabolism and Possible Mechanisms of Action in Experimental Osteoporosis.
Al-Dhubiab BE, Patel SS, Morsy MA, Duvva H, Nair AB, Deb PK, Shah J
Estrogen is instrumental in the pathological process of osteoporosis because a deficiency of this hormone increases the release of bone-resorbing cytokines. Acetyl-11-keto-β-boswellic acid (AKBA), a constituent from , has an anti-inflammatory effect by inhibiting tumor necrosis factor-α (TNF-α) expression, which leads to a decline in receptor activator of nuclear factor-kappa B (NF-κB) ligand, and consequently, a reduction in osteoclast activity. Hence, AKBA may be beneficial against bone loss during osteoporosis. Therefore, the current study intended to evaluate the beneficial effects of AKBA in ovariectomy-induced osteoporosis and to investigate its mechanism of action. Sham-operation or ovariectomy female Sprague Dawley rats were used for evaluating the antiosteoporotic effect of AKBA in this study. AKBA (35 mg/kg, p.o.) and estradiol (0.05 mg/kg, i.m.) were administered for 42 days. At the end of the experiment, body and uterus weights, serum and urine calcium and phosphorus, serum alkaline phosphatase, and urinary creatinine levels, besides serum levels of NF-κB and TNF-α were determined. Weight, length, thickness, hardness, calcium content, as well as the bone mineral density of femur bone and lumbar vertebra were measured. A histopathological examination was also carried out. AKBA ameliorated all tested parameters and restored a normal histological structure. Thus, AKBA showed good antiosteoporotic activity, which may be mediated through its suppression of the NF-κB-induced TNF-α signaling pathway.
Nutrients. 2020 Oct;12(10):.
PMID: 33081068 [PubMed - indexed for MEDLINE]
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| 11. |
A natural supplement formula reduces anti-oxidative stress and enhances osteo-chondrogenic differentiation potential in mesenchymal stem cells.
Kim DH, Kim DH, Heck BE, Shaffer M, Hur J, Yoo KH
There is great interest in using natural supplements to treat various medical conditions. In this study, we evaluated the anti-oxidative and stem cell differentiation effects of a mixture of vitamin D, , ginger, curcumin, and Boswellia extract. The calcein acetoxymethyl assay after HO treatment showed that combined natural supplement had an anti-oxidative effect. NS-J also increased calcium deposition, as shown by Alizarin Red S staining, indicating bone formation activity. The contents of type II collagen and glycosaminoglycans, which are biomarkers of cartilage, were higher in mesenchymal stem cells treated with combined natural supplement than in cells treated with individual ingredients of the formula. In mesenchymal stem cells treated with human osteoarthritis synovial fluids, combined natural supplement enhanced the expression of type II collagen and PPAR-δ, overcoming the anti-chondrogenic effect of inflammatory conditions. Combined natural supplement also inhibited Oil Red O staining in cells, which indicates inhibited adipogenesis. Thus, combined natural supplement, a formula comprising vitamin D, , ginger, curcumin and Boswellia extract, reduced oxidative stress, enhanced osteogenesis and chondrogenesis, and inhibited adipogenesis in mesenchymal stem cells to a greater extent than the individual ingredients, indicating synergistic interaction. In addition, combined natural supplement increased the expression PPAR-δ, suggesting that these effects correlate with the PPAR-δ pathway.
J Clin Biochem Nutr. 2020 May;66(3):206-212.
PMID: 32523247 [PubMed - as supplied by publisher]
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| 12. |
Untargeted metabolomics revealed therapeutic mechanisms of icariin on low bone mineral density in older caged laying hens.
Huang J, Hu Y, Tong X, Zhang L, Yu Z, Zhou Z
Osteoporosis is a common chronic disease in the elderly population and in some domestic animals. Caged layer osteoporosis (CLO) is a common bone metabolism disease that was recently recommended as an ideal animal model for osteoporosis. This study aimed to investigate the therapeutic effect and mechanism of dietary icariin (ICA), the main bioactive component of the Chinese herb Epimedium, on low bone mineral density (BMD) in older caged laying hens. A total of 216, 54-week-old Lohmann pink-shell laying hens were allocated to three groups, comprising one control group and two treatment groups that were additionally supplied with 0.5 or 2.0 g kg-1 ICA. The results showed that dietary ICA significantly increased the femur BMD by 49.3% and the tibia BMD by 38.9%, improved the microstructure of bone tissue, decreased levels of the bone metabolism index, enhanced serum antioxidant capacity and regulated messenger RNA expression of bone-related genes. ICA-induced differential metabolites were clarified by using untargeted metabolomics assays. Furthermore, correlation analysis between differential metabolites and BMD indicated that eight differential metabolites correlated highly with both femur and tibia BMD, including uridine, taurine, palmitic acid, adrenic acid, fexofenadine, lysoPC(18 : 1), lysoPE(20 : 3/0 : 0) and 3-acetyl-11-keto-beta-boswellic acid. ICA mainly perturbed pyrimidine metabolism, taurine metabolism and lipid metabolism, which led to increased BMD in older caged laying hens. These findings revealed underlying therapeutic mechanisms of dietary ICA on low BMD, and provided reference metabolites for the early diagnosis of osteoporosis.
Food Funct. 2020 Apr;11(4):3201-3212.
PMID: 32211683 [PubMed - indexed for MEDLINE]
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| 13. |
β-Elemonic acid inhibits the growth of human Osteosarcoma through endoplasmic reticulum (ER) stress-mediated PERK/eIF2α/ATF4/CHOP activation and Wnt/β-catenin signal suppression.
Zhao A, Zhang Z, Zhou Y, Li X, Li X, Ma B, Zhang Q
BACKGROUND: Osteosarcoma (OS) is a significant threat to the lives of children and young adults. Although neoadjuvant chemotherapy is the first choice of treatment for OS, it is limited by serious side-effects and cancer metastasis. β-Elemonic acid (β-EA), an active component extracted from Boswellia carterii Birdw., has been reported to exhibit potential anti-inflammatory and anticancer activities. However, the anti-tumor effects and underlying mechanisms on OS as well as pharmacokinetic characteristics of β-EA remain unknown.
PURPOSE: This study was aimed to investigating the anti-tumor effects of β-EA on human OS, the underlying mechanisms, and the pharmacokinetic and tissue distribution characteristics.
STUDY DESIGN AND METHODS: Cell viability and colony formation assays were performed to determine the effect of β-EA cell on cell proliferation. Apoptosis rates, mitochondrial membrane potential and cell cycle features were analyzed by flow cytometry. qRT-PCR, Western blot, immunofluorescence and immunohistochemical assays were conducted to evaluate the expression levels of genes or proteins related to the pathways affected by β-EA in vitro and in vivo. Cell migration and invasion were evaluated in wound healing and Transwell chamber assays. The effects and pharmacokinetic characteristics of β-EA in vivo were evaluated by analyzing tumor suppression, pharmacokinetics and tissue distribution.
RESULTS: Explorations indicated that endoplasmic reticulum (ER) stress conditions provoked by β-EA activated the PERK/eIF2α/ATF4 branch of the unfolded protein reaction (UPR), stimulating C/EBP homologous protein (CHOP)-regulated apoptosis and inducing Ca leakage leading to caspase-dependent apoptosis. Furthermore, β-EA induced G0/G1 cell cycle arrest and inhibited metastasis of HOS and 143B cells by attenuating Wnt/β-catenin signaling effects, which included decreased levels of p-Akt(Ser473), p-Gsk3β (Ser9), Wnt/β-catenin target genes (c-Myc and CyclinD1) along with a decline in nuclear β-catenin accumulation. The fast absorption, short elimination half-life, and linear pharmacokinetic characteristics of β-EA were also revealed. The distribution of β-EA was detected in the tumor and bone tissues.
CONCLUSIONS: Overall, both in vitro and in vivo investigations showed the potential of β-EA for the treatment of human OS. The pharmacokinetic profile and considerable distribution in the tumor and bone tissues warrant further preclinical or even clinical studies.
Phytomedicine. 2020 Apr;69():153183.
PMID: 32113150 [PubMed - indexed for MEDLINE]
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| 14. |
Acetyl-11-keto-β-boswellic acid attenuates titanium particle-induced osteogenic inhibition via activation of the GSK-3β/β-catenin signaling pathway.
Xiong L, Liu Y, Zhu F, Lin J, Wen D, Wang Z, Bai J, Ge G, Xu C, Gu Y, Xu Y, Zhou J, Geng D
Peri-prosthetic osteolysis (PPO) is mainly induced by wear particles and represents the leading cause of implant failure and revision surgery. Previous studies have identified mitigation of wear particle-induced inflammation and bone resorption as the main approaches to treat PPO. Recently, wear particle-induced reduction of bone formation around the prosthesis was identified as a major factor in the development of PPO. Acetyl-11-keto-β-boswellic acid (AKBA), a derivative of frankincense, has been shown to play a potential role in bone metabolism. However, whether AKBA enhances bone formation in wear particle-induced osteolysis remains unknown. In this study, we examined whether AKBA attenuates titanium particle-induced osteogenic reduction. Titanium particles were used to induce osteolysis in murine calvaria, and micro-CT and histological analyses were used to evaluate the results. Mouse osteoblast cells, MC3T3-E1 were co-cultured with titanium particles to determine their effect on osteoblast formation . We demonstrated that AKBA treatment significantly inhibited titanium particle-induced osteogenic inhibition by enhancing osteogenesis both and . AKBA treatment also enhanced the phosphorylation of GSK-3β, decreased the degradation of β-catenin, and increased the translocation of β-catenin from the cytoplasm to the nucleus. Taken together, these results showed that AKBA treatment attenuated titanium-induced osteogenic inhibition by activating the GSK-3β/β-catenin signaling pathway. These findings suggest that AKBA is a promising new target in the prevention and treatment of PPO.
Theranostics. 2019;9(24):7140-7155.
PMID: 31695758 [PubMed - indexed for MEDLINE]
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| 15. |
Pharmacological investigation of 'HIM-CHX': A herbal combination in the experimental muscle wasting condition.
Azeemuddin MM, Rao CM, Rafiq M, Babu UV, Rangesh P
Muscle wasting diseases are gradually increasing with the increase in global life expectancy. This study was designed to evaluate the efficacy of HIM-CHX, a herbal combination of Boswellia serrata, Cissus quadrangularis, and Withania somnifera, on Sarcopenia. The effects of HIM-CHX on parameters such as muscle mass, grip strength, motor coordination, gait, locomotor activity and endurance were measured in rats. In addition to this, inflammatory cytokines, myokine and growth hormone levels were also evaluated. In the first experiment, HIM-CHX was administered orally to rats at the dose of 125, 250, and 500 mg/kg body weight for 12 weeks. At the end of the treatment period, muscle mass, grip strength, motor coordination and proinflammatory cytokines were evaluated. In the second experiment, HIM-CHX was administered orally at a dose of 500 mg/kg body weight for 4 weeks and gait analysis, locomotor activity, endurance and endogenous antioxidant activity were evaluated. The animals treated with HIM-CHX showed a significant improvement in gastrocnemius muscle weight, carcass weight, gait, locomotor activity and endurance. HIM-CHX exerts its effect by reducing the levels of TNF-α, IL-6, and Myostatin while increasing the IGF-1 levels which are the typical biomarkers of muscle wasting. Furthermore, the study findings indicate that HIM-CHX has the potential to correct the pathophysiological changes associated with sarcopenia.
Exp Gerontol. 2019 Oct;125():110663.
PMID: 31319130 [PubMed - indexed for MEDLINE]
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| 16. |
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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| 17. |
Dietary Ingredients Requiring Further Research Before Evidence-Based Recommendations Can Be Made for Their Use as an Approach to Mitigating Pain.
Crawford C, Boyd C, Berry K, Deuster P,
OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons; although such use has become popular, decisions are often driven by information that is not evidence-based. This work evaluates whether current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel.
METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. Grading of Recommendations, Assessment, Development and Evaluation was used to determine confidence in the effect estimates. The committee used a decision table to make evidence-informed judgments across decision-making factors and recommendations for practice and self-care use.
RESULTS: Nineteen dietary ingredients were assessed. No recommendations were given for boswellia, ginger, rose hip, or s-adenosyl-L-methionine (SAMe); specifically, although ginger can be obtained via food, no recommendation is provided for use as a supplement due to unclear research. Further, there were insufficient strong research on boswellia and SAMe and possible compliance issues (i.e., high number of capsules required daily) associated with rose hip.
CONCLUSIONS: No recommendations were made when the evidence was low quality or trade-offs were so closely balanced that any recommendation would be too speculative. Research recommendations are provided to enhance the quality and body of evidence for the most promising ingredients. Clinicians and those with chronic pain can rely on evidence-based recommendations to inform their decisions.
Pain Med. 2019 Aug;20(8):1619-1632.
PMID: 30986310 [PubMed - indexed for MEDLINE]
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| 18. |
Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.
Crawford C, Boyd C, Paat CF, Meissner K, Lentino C, Teo L, Berry K, Deuster P
OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel.
METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use.
RESULTS: Nineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations.
CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps.
Pain Med. 2019 Jun;20(6):1236-1247.
PMID: 30986309 [PubMed - indexed for MEDLINE]
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| 19. |
Comment on: Efficacy of Curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis.
Mobasheri A, Henrotin Y
Semin Arthritis Rheum. 2019 Feb;48(4):e25-e26.
PMID: 29735172 [PubMed - indexed for MEDLINE]
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| 20. |
Effect of Boswellia serrata Resin Supplementation on Basic Chemical and Mineral Element Composition in the Muscles and Liver of Broiler Chickens.
Al-Yasiry ARM, Kiczorowska B, Samolińska W
Supplementation of broiler chicken diets with resin rich in bioactive components, such as different boswellic acids, could improve productivity, chemical composition, and nutritive value of produced meat. The aim of the study was to assess the effect of different levels of Boswellia serrata (BSR) supplementation in broiler chicken diet on the basic chemical composition and the Ca, P, Mg, Fe, Zn, and Cu contents in the breast and drumstick muscles and liver. The analyses involved 200 Ross 308 chickens. The broiler chickens were fed with diets containing 0 (BSR0), 1.5 (BSR1.5), 2 (BSR2), and 2.5% (BSR2.5) of B. serrata resin. The supplementation of broiler chicken diets with 2.5% (BSR2.5) decreased linearly the ether extract in breast and drumstick muscles and the calorific value in drumstick muscles (P < 0.05). An increased level of Ca in the breast and drumstick muscles (control vs. BSR diets, linear, P < 0.05) and in the liver (control vs. BSR diets, quadratic, P < 0.05) as well as Mg in the drumstick muscles and liver (control vs. BSR diets, linear, P < 0.05) was noted in the BSR2 and BSR2.5 chicken groups. The BSR supplementation reduced Cu (in the breast and drumstick muscles and liver) (P < 0.05) and Zn retention (in the drumstick muscles) (C vs. BSR, linear, P < 0.05). B. serrata resin can be considered a good feed additive with a positive impact on the dietary value of poultry meat.
Biol Trace Elem Res. 2017 Oct;179(2):294-303.
PMID: 28210929 [PubMed - indexed for MEDLINE]
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| 21. |
Co-analgesic therapy for arthroscopic supraspinatus tendon repair pain using a dietary supplement containing Boswellia serrata and Curcuma longa: a prospective randomized placebo-controlled study.
Merolla G, Dellabiancia F, Ingardia A, Paladini P, Porcellini G
BACKGROUND: The cuff tendon that is most prone to full-thickness rotator cuff tears is the supraspinatus (SSP). Arthroscopic SSP repair ensures good to satisfactory mid- to long-term clinical outcomes. However, the intense postoperative pain reduces rehabilitation compliance and is cause of patient dissatisfaction. Many natural compounds act by inhibiting inflammatory pathways in a similar way to anti-inflammatory drugs
MATERIALS AND METHODS: This was a prospective randomized trial designed to assess the analgesic effect of a dietary supplement (DS) containing Boswellia serrata and Curcuma longa in a population of subjects with full-thickness SSP tendon tear treated by arthroscopy. Three weeks before surgery, patients were randomized to receive Tendisulfur(®) (group T) or a placebo (group P) for 2 months. The primary outcome measure was subjective VAS pain. Secondary outcomes measures were Constant-Murley score simple shoulder test, and patient global assessment (PGA) scores. Patients were assessed immediately at baseline and subsequently at 1, 2, 4, 6, 8, 12, and 24 weeks.
RESULTS: Stratification of pain scores and subscores demonstrated significantly lower overall pain scores in group T versus group P at 1 week (p = 0.0477), and lower but not significantly different scores on week 2 (p = 0.0988); at subsequent time points, differences were not significant (p > 0.05). PGA scores were good in all subjects.
CONCLUSIONS: In conclusion, this study provides objective data on the effect of a DS containing natural substances, added to standard analgesics, on postoperative RC pain. DS alleviated short and partially mid-term pain, while long-term pain was unchanged. This limitation can probably be addressed by a dosage increase over the first 4 weeks and by extending treatment by 1 or 2 months.
Musculoskelet Surg. 2015 Sep;99 Suppl 1():S43-52.
PMID: 25957549 [PubMed - indexed for MEDLINE]
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| 22. |
Ayurvedic interventions for osteoarthritis: a systematic review and meta-analysis.
Kessler CS, Pinders L, Michalsen A, Cramer H
Ayurveda is one of the fastest growing systems within complementary and alternative medicine. However, the evidence for its effectiveness is unsatisfactory. The aim of this work was to review and meta-analyze the effectiveness and safety of different Ayurvedic interventions in patients with osteoarthritis (OA). 138 electronic databases were searched through August 2013. Randomized controlled trials, randomized crossover studies, cluster-randomized trials, and non-randomized controlled clinical trials were eligible. Adults with pre-diagnosed OA were included as participants. Interventions were included as Ayurvedic if they were explicitly labeled as such. Main outcome measures were pain, physical function, and global improvement. Risk of bias was assessed using the Cochrane risk of bias tool. 19 randomized and 14 non-randomized controlled trials on 12 different drugs and 3 non-pharmaceutical interventions with a total of 2,952 patients were included. For the compound preparation, Rumalaya, large and apparently unbiased effects beyond placebo were found for pain (standardized mean difference [SMD] -3.73; 95 % confidence interval [CI] -4.97, -2.50; P < 0.01) and global improvement (risk ratio 12.20; 95 % CI 5.83, 25.54; P < 0.01). There is also some evidence that effects of the herbal compound preparation Shunti-Guduchi are comparable to those of glucosamine for pain (SMD 0.08; 95 % CI -0.20, 0.36; P = 0.56) and function (SMD 0.15; 95 % CI -0.12, 0.36; P = 0.41). Based on single trials, positive effects were found for the compound preparations RA-11, Reosto, and Siriraj Wattana. For Boswellia serrata, Lepidium Sativum, a Boswellia serrata containing multicomponent formulation and the compounds Nirgundi Taila, Panchatikta Ghrita Guggulu, and Rhumayog, and for non-pharmacological interventions like Ayurvedic massage, steam therapy, and enema, no evidence for significant effects against potential methodological bias was found. No severe adverse events were observed in all trials. The drugs Rumalaya and Shunti-Guduchi seem to be safe and effective drugs for treatment of OA-patients, based on these data. However, several limitations relate to clinical research on Ayurveda. Well-planned, well-conducted and well-published trials are warranted to improve the evidence for Ayurvedic interventions.
Rheumatol Int. 2015 Feb;35(2):211-32.
PMID: 25062981 [PubMed - indexed for MEDLINE]
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| 23. |
Boswellia frereana (frankincense) suppresses cytokine-induced matrix metalloproteinase expression and production of pro-inflammatory molecules in articular cartilage.
Blain EJ, Ali AY, Duance VC
The aim of this study was to assess the anti-inflammatory efficacy of Boswellia frereana extracts in an in vitro model of cartilage degeneration and determine its potential as a therapy for treating osteoarthritis. Cartilage degradation was induced in vitro by treating explants with 5 ng/ml interleukin1alpha (IL-1alpha) and 10 ng/ml oncostatin M (OSM) over a 28-day period, in the presence or absence of 100 microg/ml B. frereana. Treatment of IL-1alpha/OSM stimulated cartilage explants with B. frereana inhibited the breakdown of the collagenous matrix. B. frereana reduced MMP9 and MMP13 mRNA levels, inhibited MMP9 expression and activation, and significantly reduced the production of nitrite (stable end product of nitric oxide), prostaglandin E2 and cycloxygenase-2. Epi-lupeol was identified as the principal constituent of B. frereana. This is the first report on the novel anti-inflammatory properties of Boswellia frereana in an in vitro model of cartilage degradation. We have demonstrated that B. frereana prevents collagen degradation, and inhibits the production of pro-inflammatory mediators and MMPs. Due to its efficacy we propose that B. frereana should be examined further as a potential therapeutic agent for treating inflammatory symptoms associated with arthritis.
Phytother Res. 2010 Jun;24(6):905-12.
PMID: 19943332 [PubMed - indexed for MEDLINE]
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| 24. |
Role of Sandhika: a polyherbal formulation on MC3T3-E1 osteoblast-like cells.
Tripathi YB, Tripathi P, Korlagunta K, Chai SC, Smith BJ, Arjmandi BH
Sandhika is a polyherbal formulation, (water soluble fraction of Commiphora mukul, Boswellia serrata, Semecarpus anacardium and Strychnos nux vomica), which has been in clinical use in India for last 20 years. Its modified formulation BHUx has shown specific inhibition of cyclooxygenase (COX)-2 and lipoxygenase (LOX)-15 and has prevented diet-induced atherosclerosis in rabbits. In order to explore the possibility of the use of Sandhika for the management of osteoporosis, we have examined its influence on MC3T3-E1 osteoblast-like cells in presence of lipopolysaccharide (1 microg/ml) in terms of calcium nodule formation and alkaline phosphatase activity. MC3T3-E1 osteoblast-like cells (80% confluence in 6-well plates) were treated with water extract of Sandhika, for 10 days, in the concentration range of 0.5 to 16 mg/ml final concentration, in presence of LPS. Media was changed on every third day and culture supernatant was collected after every change to assess the alkaline phosphatase activity and on the tenth day, cells were washed and stained with "Alizarin S" for visualization of calcium nodules by using Meta Morph software (Universal Imaging, Downingtown, PA). The results showed significant enhancement in calcium nodule formation in the dose dependent manner up to 2 mg/ml, followed by gradual decrease at higher concentrations. This change was accompanied with the increase in the alkaline phosphatase activity in these plates, indicating a potential anabolic effect of this polyherbal formulation on osteoblast-like cells under inflammatory conditions induced by LPS.
Inflammation. 2008 Feb;31(1):1-8.
PMID: 17687634 [PubMed - indexed for MEDLINE]
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| 25. |
Acetyl-11-keto-beta-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-kappa B and NF-kappa B-regulated gene expression.
Takada Y, Ichikawa H, Badmaev V, Aggarwal BB
Acetyl-11-keto-beta-boswellic acid (AKBA), a component of an Ayurvedic therapeutic plant Boswellia serrata, is a pentacyclic terpenoid active against a large number of inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and bronchial asthma, but the mechanism is poorly understood. We found that AKBA potentiated the apoptosis induced by TNF and chemotherapeutic agents, suppressed TNF-induced invasion, and inhibited receptor activator of NF-kappaB ligand-induced osteoclastogenesis, all of which are known to require NF-kappaB activation. These observations corresponded with the down-regulation of the expression of NF-kappaB-regulated antiapoptotic, proliferative, and angiogenic gene products. As examined by DNA binding, AKBA suppressed both inducible and constitutive NF-kappaB activation in tumor cells. It also abrogated NF-kappaB activation induced by TNF, IL-1beta, okadaic acid, doxorubicin, LPS, H2O2, PMA, and cigarette smoke. AKBA did not directly affect the binding of NF-kappaB to the DNA but inhibited sequentially the TNF-induced activation of IkappaBalpha kinase (IKK), IkappaBalpha phosphorylation, IkappaBalpha ubiquitination, IkappaBalpha degradation, p65 phosphorylation, and p65 nuclear translocation. AKBA also did not directly modulate IKK activity but suppressed the activation of IKK through inhibition of Akt. Furthermore, AKBA inhibited the NF-kappaB-dependent reporter gene expression activated by TNFR type 1, TNFR-associated death domain protein, TNFR-associated factor 2, NF-kappaB-inducing kinase, and IKK, but not that activated by the p65 subunit of NF-kappaB. Overall, our results indicated that AKBA enhances apoptosis induced by cytokines and chemotherapeutic agents, inhibits invasion, and suppresses osteoclastogenesis through inhibition of NF-kappaB-regulated gene expression.
J Immunol. 2006 Mar;176(5):3127-40.
PMID: 16493072 [PubMed - indexed for MEDLINE]
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| 26. |
Boswellic acids and protease activities.
Rall B, Ammon HP, Safayhi H
The involvement of human leukocyte elastase (HLE) in several inflammatory processes and the reported inhibitory effect of ursolic acid on HLE has prompted the authors to start investigation on the effects of acetyl-11-keto-β-boswellic acid (AKBA) on serine proteinases including HLE.
Phytomedicine. 1996 May;3(1):75-6.
PMID: 23194866 [PubMed - as supplied by publisher]
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