| 1. |
[Optimal processing technology of Zhangbang vinegar-processed Olibanum with multi-indicator-response surface methodology and anticoagulant effect evaluation].
Xiao XL, Yan GM, Gong QF, Yu H, Yang DY, Wu XY, Zhu YH, Peng XL
This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P<0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.
Zhongguo Zhong Yao Za Zhi. 2023 Aug;48(16):4402-4412.
PMID: 37802866 [PubMed - indexed for MEDLINE]
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| 2. |
The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK.
AlTamimi JZ, AlFaris NA, Alshammari GM, Alagal RI, Aljabryn DH, Yahya MA
This study examined the protective effect of 11-keto-β-boswellic acid (AKBA) against streptozotocin (STZ)-induced diabetic cardiomyopathy (DC) in rats and examined the possible mechanisms of action. Male rats were divided into 5 groups (n = 8/each): (1) control, AKBA (10 mg/kg, orally), STZ (65 mg/kg, i.p.), STZ + AKBA (10 mg/kg, orally), and STZ + AKBA + compound C (CC/an AMPK inhibitor, 0.2 mg/kg, i.p.). AKBA improved the structure and the systolic and diastolic functions of the left ventricles (LVs) of STZ rats. It also attenuated the increase in plasma glucose, plasma insulin, and serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), and free fatty acids (FFAs) in these diabetic rats. AKBA stimulated the ventricular activities of phosphofructokinase (PFK), pyruvate dehydrogenase (PDH), and acetyl CoA carboxylase (ACC); increased levels of malonyl CoA; and reduced levels of carnitine palmitoyltransferase I (CPT1), indicating improvement in glucose and FA oxidation. It also reduced levels of malondialdehyde (MDA); increased mitochondria efficiency and ATP production; stimulated mRNA, total, and nuclear levels of Nrf2; increased levels of glutathione (GSH), heme oxygenase (HO-1), superoxide dismutase (SOD), and catalase (CAT); but reduced the expression and nuclear translocation of NF-κB and levels of tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These effects were concomitant with increased activities of AMPK in the LVs of the control and STZ-diabetic rats. Treatment with CC abolished all these protective effects of AKBA. In conclusion, AKBA protects against DC in rats, mainly by activating the AMPK-dependent control of insulin release, cardiac metabolism, and antioxidant and anti-inflammatory effects.
Nutrients. 2023 Mar;15(7):.
PMID: 37049501 [PubMed - indexed for MEDLINE]
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| 3. |
[Corrigendum] Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-β-boswellic acid in combination on isoproterenol-induced myocardial injury in rats.
Chen M, Wang M, Yang Q, Wang M, Wang Z, Zhu Y, Zhang Y, Wang C, Jia Y, Li Y, Wen A
Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the OGD + HYSA and OGD + HYSA + AKBA plots in Fig. 5B on p. 1507 appeared to share a similar patterning with respect to many of the data points. The authors have re-examined their original data and realize that they made inadvertent errors during the assembly of this figure. The FCS files were read and analyzed by FlowJo cell analysis software. The authors have carefully examined the raw data (fcs files), and have identified the errors that occurred when applying the setting to all files and saving the resulting fluorescence data to dot-plot graphs. The corrected version of Fig. 5, showing the correct flow cytometric analysis data in Fig. 5B and a re-evaluation of the quantification of the data in the associated bar chart, is shown on the next page. Note that the errors made during the assembly of this figure did not affect the major conclusions reported in the paper. All the authors have agreed to this Corrigendum, and thank the Editor of for allowing them the opportunity to publish this. The authors regret these errors went unnoticed prior to the publication of the paper, and apologize to the readership for any confusion that this may have caused. [the original article was published in 37: 1501-1510, 2016; DOI: 10.3892/ijmm.2016.2571].
Int J Mol Med. 2022 Jan;49(1):.
PMID: 34850962 [PubMed - as supplied by publisher]
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| 4. |
Boswellic acid protects against Bisphenol-A and gamma radiation induced hepatic steatosis and cardiac remodelling in rats: role of hepatic PPAR-α/P38 and cardiac Calcineurin-A/NFATc1/P38 pathways.
Thabet NM, Abdel-Rafei MK, Moustafa EM
Bisphenol-A (BPA) and gamma-radiation are two risky environmental pollutants that human beings are exposed to in everyday life and consequently they threaten human health via inducing oxidative stress, inflammation, and eventually tissue damage. This study aims at appraising the protective effect of Boswellic Acid (BA) (250 mg/kg/day, orally) administration on BPA (150 mg/kg/day, i.p) and γ-irradiation (IR) (3 Gy/week for 4 weeks up to cumulative dose of 12 Gy/experimental course) for 4 weeks-induced damage to liver and heart tissues of rats. The present results indicated a significant improvement against damage induced by BPA and IR revealed in biochemical investigations (hepatic PPAR-α/P38 and cardiac ET-1/Calcineurin-A/NFATc1/P38) and histopathological examination of liver and heart. It could be concluded that BA possesses a protective effect against these two deleterious environmental pollutants which attracted major global concerns due to their serious toxicological impact on human health.
Arch Physiol Biochem. 2022 Jun;128(3):767-785.
PMID: 32057248 [PubMed - indexed for MEDLINE]
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| 5. |
Acetyl-11-keto-β-boswellic acid alleviates myocardial fibrosis injury by inhibiting the TGF-β1/Smads pathway and activating the Nrf2/HO-1 pathway.
Hou X, Gao B, Han Q, Wang Q, Liang H, Huo Q
Minerva Med. 2020 Jun;111(3):285-288.
PMID: 31345015 [PubMed - indexed for MEDLINE]
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| 6. |
Anti-Inflammatory Activity of Extracts: An Study on Porcine Aortic Endothelial Cells.
Bertocchi M, Isani G, Medici F, Andreani G, Tubon Usca I, Roncada P, Forni M, Bernardini C
This study is aimed at investigating the cytotoxicity, anti-inflammatory, and angiogenic activities of two extracts on primary culture of porcine aortic endothelial cells (pAECs). Chemical characterization of a dry extract (extract A) and a hydroenzymatic extract (extract G) of was performed by HPLC using pure boswellic acids (BAs) as standard. In cultured pAECs, extract G improved cell viability, following LPS challenge, in a dose-dependent manner and did not show any toxic effect. On the other hand, extract A was toxic at higher doses and restored pAEC viability after LPS challenge only at lower doses. Pure BAs, used at the same concentrations as those determined in the phytoextracts, did not contrast LPS-induced cytotoxicity. Extract A showed proangiogenic properties at the lowest dose, and the same result was observed using pure AKBA at the corresponding concentration, whereas extract G did not show any effect on the migration capacity of endothelial cells. In conclusion, an anti-inflammatory activity of extracts on endothelial cells was reported, though cytotoxicity or proliferative stimulation can occur instead of a protective effect, depending on the dose and the formulation.
Oxid Med Cell Longev. 2018;2018():2504305.
PMID: 30046370 [PubMed - indexed for MEDLINE]
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| 7. |
Medicinal plants with antithrombotic property in Persian medicine: a mechanistic review.
Memariani Z, Moeini R, Hamedi SS, Gorji N, Mozaffarpur SA
Thrombosis is one of the major causes of morbidity and mortality in a wide range of vessels diseases. Due to the high prevalence of thromboembolic disorders investigations are being carried out on new antithrombotic agents with limited adverse side effects in which herbal medicines are considered as alternative remedies. Persian medicine (PM) as a traditional medicine has a good potential for pharmacotherapy based on its own principles and development of drugs via investigating PM literature. In PM manuscripts there are some concepts that express the management of blood clots and antithrombotic properties. This study reviewed the pharmacological effects of medicinal plants mentioned in PM literature for blood clot management in light of current knowledge. Plants mentioned in PM for management of blood clot belong to 12 families in which Apiaceae, Lamiaceae and Compositae were the most repeated ones. Among the proposed plants Allium sativum, Rosmarinus officinalis, Boswellia serrata, Sesamum indicum, Matricaria chamomilla and Carthamus tinctorius have been the most researched plants in modern antithrombotic studies while for some plants such as Helichrysum stoechas, Dracocephalum kotschi, Carum carvi, Bunium persicum and Lagoecia cuminoides no evidence could be found. One of the interesting notes in clot management in PM texts was introducing the target organ for some of the recommended herbs like Carum carvi and Bunium persicum for dissolving blood clot in stomach and Commiphora mukul for thrombosed hemorrhoid. It seems review of PM recommendations can help to design future researches for antithrombotic drugs discovering with more effectiveness and safety.
J Thromb Thrombolysis. 2018 Jan;45(1):158-179.
PMID: 29124622 [PubMed - indexed for MEDLINE]
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| 8. |
Defined Structure-Activity Relationships of Boswellic Acids Determine Modulation of Ca2+ Mobilization and Aggregation of Human Platelets by Boswellia serrata Extracts.
Siemoneit U, Tausch L, Poeckel D, Paul M, Northoff H, Koeberle A, Jauch J, Werz O
Boswellic acids constitute a group of unique pentacyclic triterpene acids from with multiple pharmacological activities that confer them anti-inflammatory and anti-tumoral properties. A subgroup of boswellic acids, characterized by an 11-keto group, elevates intracellular Ca concentrations [Ca] and causes moderate aggregation of human platelets. How different BAs and their mixtures in pharmacological preparations affect these parameters in activated platelets has not been addressed, so far. Here, we show that boswellic acids either antagonize or induce Ca mobilization and platelet aggregation depending on defined structural determinants with inductive effects predominating for a gum resin extract. 3--Acetyl-11-keto--boswellic acid potently suppressed Ca mobilization (IC = 6 µM) and aggregation (IC = 1 µM) when platelets were activated by collagen or the thromboxane A receptor agonist U-46619, but not upon thrombin. In contrast, -boswellic acid and 3--acetyl--boswellic acid, which lack the 11-keto moiety, were weak inhibitors of agonist-induced platelet responses, but instead they elicited elevation of [Ca] and aggregation of platelets (≥ 3 µM). 11-Keto--boswellic acid, the structural intermediate between 3--acetyl-11-keto--boswellic acid and -boswellic acid, was essentially inactive independent of the experimental conditions. Together, our study unravels the complex agonizing and antagonizing properties of boswellic acids on human platelets in pharmacologically relevant preparations of gum extracts and prompts for careful evaluation of the safety of such extracts as herbal medicine in cardiovascular risk patients.
Planta Med. 2017 Aug;83(12-13):1020-1027.
PMID: 28403501 [PubMed - indexed for MEDLINE]
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| 9. |
Acetyl-11-Keto-β-Boswellic Acid Attenuates Prooxidant and Profibrotic Mechanisms Involving Transforming Growth Factor-β1, and Improves Vascular Remodeling in Spontaneously Hypertensive Rats.
Shang P, Liu W, Liu T, Zhang Y, Mu F, Zhu Z, Liang L, Zhai X, Ding Y, Li Y, Wen A
Vascular remodeling is an important complication of hypertension with oxidative stress-related profibrotic pathways involved. The transforming growth factor β1 (TGF-β1) has been shown to be a potential target of vasoprotection, and has multiple roles in vascular remodeling. Acetyl-11-Keto-β-Boswellic Acid (AKBA) is one of the active principles of Boswellic acids, and shows antioxidant activity in many diseases. The study is to determine effects of AKBA on systemic oxidative stress of hypertension and vascular remodeling. In the experiments, spontaneously hypertensive rats (SHR) were used. And in vitro, fibroblast was pretreated with AKBA before Ang II stimuli. In the results, treatment of AKBA markedly reduced oxidative stress, and decreased vascular remodeling by restoring vascular wall parameters and improving vascular reactivity. AKBA dramatically reduced TGF-β1 and Smad3 expression, as shown in immunofluorescence and immunohistochemistry. In cultured fibroblast, AKBA decreased intracellular ROS levels. Cell viability and proliferation, as well as migration were inhibited by AKBA. Additionally, treatment of AKBA significantly decreased TGF-β1 secretion in culture supernatant. Expression of TGF-β1, Smad3, P-Smad3 and Smad7 were also decreased by AKBA in fibroblast. In conclusion, AKBA is able to attenuate oxidative stress and profibrotic mechanisms, and improve vascular remodeling in hypertension through TGF-β1/Smad3 pathway.
Sci Rep. 2016 Dec;6():39809.
PMID: 28009003 [PubMed - indexed for MEDLINE]
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| 10. |
Anti-aggregatory effect of boswellic acid in high-fat fed rats: involvement of redox and inflammatory cascades.
Tawfik MK
INTRODUCTION: A high-fat diet is one of the main dietary factors promoting platelet aggregation. The present study was conducted to elucidate the involvement of boswellic acid (BA) on the platelet hyperaggregability in HFD-fed rats. As platelet hyperaggregability in HFD rats is closely linked to inflammation and enhanced free radical production, the present study was extended to evaluate the anti-inflammatory and anti-oxidative effect of BA on HFD-promoted platelet aggregation.
MATERIAL AND METHODS: Rats were assigned to normal, HFD-fed, aspirin-treated (30 mg/kg), and BA-treated (250 and 500 mg/kg) groups.
RESULTS: Boswellic acid administration in a high dose was effective in attenuating the severity of hyperlipidemia and platelet aggregation, indicated by lower collagen/epinephrine-induced platelet aggregation, as evidenced by the significant increase ( < 0.05) in the circulating platelet count and reduction in the number of thrombi in the lungs. Moreover, it attenuated the oxidative stress and the intensity of inflammatory mediators associated with platelet hyperaggregability, as evidenced by the inhibitory effects on interlukin-1β, COX-2 and tumor necrosis factor-α, indicating that the antiplatelet activity of BA is likely a consequence of controlling oxidative stress and inflammation.
CONCLUSIONS: The present data suggest that BA shows a promising anti-aggregatory effect by attenuating the enhanced hyperlipidemia, oxidative stress and inflammation associated with HFD.
Arch Med Sci. 2016 Dec;12(6):1354-1361.
PMID: 27904529 [PubMed - as supplied by publisher]
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| 11. |
Protective Effects of α-Boswellic Acids in a Pulmonary Arterial Hypertensive Rat Model.
Xiao B, Zhang G, Ali Sheikh MS, Shi R
The purpose of this study was to observe the protective effects of α-boswellic acids on hypoxia-induced pulmonary vascular structural remodeling in pulmonary arterial smooth muscle cells in a hypertensive rat model. Pulmonary arterial smooth muscle cells were cultured and then randomly divided into four groups: normoxia, hypoxia (3 % O2; 24 h), hypoxia plus α-boswellic acids, and hypoxia plus DMSO (as a positive control), according to the different concentrations of α-boswellic acids (21.90 µM, 43.79 µM, and 87.58 µM). Apoptosis and proliferation of pulmonary arterial smooth muscle cells significantly decreased in the hypoxia plus α-boswellic acids group compared with the hypoxia and hypoxia plus DMSO groups (n = 8, p < 0.05). The mRNA and protein phosphorylation levels of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 were significantly elevated in hypoxic cells compared with normal cells. However, the mRNA and protein phosphorylation levels of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 markedly decreased in the hypoxia plus α-boswellic acids group compared with the hypoxia plus DMSO group (n = 8, p < 0.05; n = 13, p < 0.05, respectively). Our findings suggest that α-boswellic acids can inhibit inappropriate apoptosis and excessive proliferation of pulmonary arterial smooth muscle cells and pulmonary vascular remodeling by repressing the expression of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 under hypoxic conditions.
Planta Med. 2017 Jan;83(1-02):78-86.
PMID: 27367920 [PubMed - indexed for MEDLINE]
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| 12. |
Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-β-boswellic acid in combination on isoproterenol-induced myocardial injury in rats.
Chen M, Wang M, Yang Q, Wang M, Wang Z, Zhu Y, Zhang Y, Wang C, Jia Y, Li Y, Wen A
Oxidative stress plays an important role in the initiation and development of myocardial injury (MI). The peroxisome proliferator-activated receptor gamma coactivator-1α (PGC‑1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is considered to be a potential target for cardioprotection in MI. Acetyl-11-keto-β-boswellic acid (AKBA) is the major organic acid component extracted from Boswellia serrata Roxb. ex Colebr. Hydroxysafflor yellow A (HSYA) is the principal active constituent of Carthamus tinctorius L. In the present study, we aimed to investigate the cardioprotective effects of HSYA and AKBA in combination in vivo and in vitro, as well as the underlying mechanisms responsible for these effects. For this purpose, MI was produced in Sprague-Dawley rats by subcutaneous injection with isoproterenol. To model ischemic-like conditions in vitro, H9C2 cells were subjected to oxygen-glucose deprivation (OGD). The levels of creatine kinase-MB (CK‑MB), lactate dehydrogenase (LDH), malondialdehyde (MDA) as well as superoxide dismutase (SOD) activity were examined as well as apoptotic cell death. Mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm or MMP) were measured using MitoSOX Red and 5,5',6,6'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) dye. The expression of PGC-1α and Nrf2 was quantified by western blot analysis and immunohistochemistry. HSYA and AKBA prevented myocardial pathological changes, significantly reduced the blood levels of CK-MB and LDH, and decreased apoptotic cell death. They significantly increased the expression of PGC-1α and Nrf2, and the activity of the antioxidant enzyme SOD and also decreased the levels of MDA and ROS. Moreover, the reduction in MMP was partly prevented by HSYA and AKBA. Taken together, these findings elucidate the underlying mechanisms through which HSYA and AKBA protect against MI. Additionally, HSYA and AKBA appear to act synergistically in order to exert cardioprotective effects.
Int J Mol Med. 2016 Jun;37(6):1501-10.
PMID: 27121241 [PubMed - indexed for MEDLINE]
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| 13. |
Pretreatment with β-Boswellic Acid Improves Blood Stasis Induced Endothelial Dysfunction: Role of eNOS Activation.
Wang M, Chen M, Ding Y, Zhu Z, Zhang Y, Wei P, Wang J, Qiao Y, Li L, Li Y, Wen A
Vascular endothelial cells play an important role in modulating anti-thrombus and maintaining the natural function of vascular by secreting many active substances. β-boswellic acid (β-BA) is an active triterpenoid compound from the extract of boswellia serrate. In this study, it is demonstrated that β-BA ameliorates plasma coagulation parameters, protects endothelium from blood stasis induced injury and prevents blood stasis induced impairment of endothelium-dependent vasodilatation. Moreover, it is found that β-BA significantly increases nitric oxide (NO) and cyclic guanosine 3', 5'-monophosphate (cGMP) levels in carotid aortas of blood stasis rats. To stimulate blood stasis-like conditions in vitro, human umbilical vein endothelial cells (HUVECs) were exposed to transient oxygen and glucose deprivation (OGD). Treatment of β-BA significantly increased intracellular NO level. Western blot and immunofluorescence as well as immunohistochemistry reveal that β-BA increases phosphorylation of enzyme nitric oxide synthase (eNOS) at Ser1177. In addition, β-BA mediated endothelium-dependent vasodilatation can be markedly blocked by eNOS inhibitor L-NAME in blood stasis rats. In OGD treated HUEVCs, the protective effect of β-BA is attenuated by knockdown of eNOS. In conclusion, the above findings provide convincing evidence for the protective effects of β-BA on blood stasis induced endothelial dysfunction by eNOS signaling pathway.
Sci Rep. 2015 Oct;5():15357.
PMID: 26482008 [PubMed - indexed for MEDLINE]
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| 14. |
Triggering of Suicidal Erythrocyte Death Following Boswellic Acid Exposure.
Calabrò S, Alzoubi K, Faggio C, Laufer S, Lang F
BACKGROUND/AIMS: The antinflammatory natural product boswellic acid is effective against cancer at least in part by inducing tumor cell apoptosis. Similar to apoptosis of nucleated cells erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca(2+)-activity ([Ca(2+)]i), energy depletion, ceramide formation and p38 kinase activation. The present study tested, whether and how boswellic acid induces eryptosis.
METHODS: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofuorescein diacetate (DCFDA) fluorescence, and cytosolic ATP concentration utilizing a luciferin-luciferase assay kit.
RESULTS: A 24 hours exposure of human erythrocytes to boswellic acid (5 µg/ml) significantly increased the percentage of annexin-V-binding cells (to 9.3 ± 0.9 %) and significantly decreased forward scatter. Boswellic acid did not significantly modify [Ca(2+)]i, cytosolic ATP, ROS, or ceramide abundance. The effect of boswellic acid on annexin-V-binding was significantly blunted, but not abolished by p38 kinase inhibitors skepinone (2 µM) and SB203580 (2 µM).
CONCLUSIONS: Boswellic acid stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on p38 protein kinase activity.
Cell Physiol Biochem. 2015;37(1):131-42.
PMID: 26303375 [PubMed - indexed for MEDLINE]
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| 15. |
Boswellic acids synergize antitumor activity and protect against the cardiotoxicity of doxorubicin in mice bearing Ehrlich's carcinoma.
Ali SA, Zaitone SA, Moustafa YM
This study aimed to test whether boswellic acids add to the antitumor effects of doxorubicin against solid tumors of Ehrlich's ascites carcinoma (EAC) grown in mice, and to investigate the protective effects of boswellic acids against doxorubicin-induced cardiotoxicity. Sixty-four female Swiss albino mice bearing EAC solid tumors were distributed among 8 groups as follows: group 1, EAC control group; group 2, doxorubicin treatment group [mice were injected with doxorubicin (6 mg·(kg body mass)(-1)·week(-1)) for 3 weeks]; groups 3-5, these mice were treated with boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively; groups 6-8, these mice were treated with a combination of doxorubicin and boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively, for 3 weeks. The results indicated that boswellic acids synergized the antitumor activity of doxorubicin. Doxorubicin-treated mice showed elevated serum activities of lactate dehydrogenase and creatine kinase isoenzyme MB as well as cardiac malondialdehyde. Further, decreases in cardiac levels of reduced glutathione, superoxide dismutase, and catalase activities were observed. These effects were accompanied by an increase in cardiac expression of caspase 3. Thus, treatment with boswellic acids attenuated doxorubicin-evoked disturbances in the above-mentioned parameters, highlighting antioxidant and antiapoptotic activities. Therefore, boswellic acids could be potential candidates for ameliorating the cardiotoxicity of doxorubicin.
Can J Physiol Pharmacol. 2015 Aug;93(8):695-708.
PMID: 26230640 [PubMed - indexed for MEDLINE]
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| 16. |
Comparative studies of pharmacokinetics and anticoagulatory effect in rats after oral administration of Frankincense and its processed products.
Pan YN, Liang XX, Niu LY, Wang YN, Tong X, Hua HM, Zheng J, Meng DY, Liu XQ
ETHNOPHARMACOLOGICAL RELEVANCE: Frankincense (FRA), Ruxiang, is the resin of Boswellia carterii Birdw and Boswellia bhaw-dajiana Birdw which has been used for centuries as formulas to improve the circulation and to relieve pain against carbuncles. Stir-fried Frankincense (SFF) and vinegar processed Frankincense (VPF) are two major processed Frankincense, and the processing procedures reportedly enhance the curative efficacy or reduce the side effects of FRA. This paper describes the comparisons in plasma pharmacokinetic behaviors of 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA) in FRA and its processed products, and their effects on coagulation factors and blood clotting tetrachoric, using an acute cold blood-stasis animal model after oral administration of FRA, SFF, and VPF.
MATERIALS AND METHODS: For pharmacokinetic study, Sprague-Dawley (SD) rats were randomly divided into three groups, including group FRA, group SFF and group VPF. And the plasma samples were analyzed by HPLC. For study of anticoagulatory effect, SD rats were randomly divided into six groups, including control, acute cold blood-stasis model, Fu-fang-dan-shen tablet- (0.75g/kg), FRA-, SFF-, and VPF-treated (2.7g/kg) groups, respectively. The serum contents of thrombin-antithrombin complex (TAT), D-dimer (D-D), and prostacyclin (PGI2) of each group were measured by ELISA. The values of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were also assessed by hematology analyzer.
RESULTS: Significantly increased levels of Cmax, AUC, T1/2, and MRT were found in rats treated with the processed products. In addition, decreased levels of D-D and TAT and increased contents of PGI2 were observed in rats given FRA and its processed products, compared with that of the model group. Moreover, VPF improved anticoagulation more than SFF in the animals.
CONCLUSIONS: The observed improvement of anticoagulation by processed FRA may result from the increased absorption and bioavailability of triterpenoids.
J Ethnopharmacol. 2015 Aug;172():118-23.
PMID: 26117531 [PubMed - indexed for MEDLINE]
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| 17. |
Acetyl-11-keto-β-boswellic acid reduces retinal angiogenesis in a mouse model of oxygen-induced retinopathy.
Lulli M, Cammalleri M, Fornaciari I, Casini G, Dal Monte M
Retinal diseases characterized by pathologic retinal angiogenesis are the leading causes of blindness worldwide. Although therapies directed toward vascular endothelial growth factor (VEGF) represent a significant step forward in the treatment of proliferative retinopathies, further improvements are needed. In the last few years, an intense research activity has focused around the use of herbal and traditional natural medicines as an alternative for slowing down the progression of proliferative retinopathies. In the present study, we investigated the antiangiogenic effects of acetyl-11-keto-β-boswellic acid (AKBA), one of the active principles derived from the plant Boswellia serrata, used in Ayurvedic systems of medicine. We studied the antiangiogenic properties of AKBA using the mouse model of oxygen-induced retinopathy (OIR), which mimics the neovascular response seen in human retinopathy of prematurity. We first evaluated the effects of subcutaneously administered AKBA on the expression/activity of proteins which are known to play a role in the OIR model. In the retina, AKBA increased expression and activity of Src homology region 2 domain-containing phosphatase 1 and reduced the phosphorylation of the transcription factor signal transducer and activator of transcription 3 (STAT3) as well as VEGF expression and VEGF receptor (VEGFR)-2 phosphorylation. Likely as a result of these effects, AKBA significantly reduced retinal neovascularization in OIR mice without affecting retinal cell survival and retinal function. Using retinal explants cultured in hypoxia and an activator of STAT3 phosphorylation, we showed that the AKBA-induced inhibition of VEGFR-2 phosphorylation is likely to be mediated by a mechanism depending on an SHP-1/STAT3/VEGF axis. In the OIR model, neovascularization results from the activation of retinal endothelial cells, therefore we evaluated whether AKBA affected the angiogenic response of human retinal microvascular endothelial cells (HRMECs). We observed that AKBA reduced proliferation, migration and tube formation in HRMECs stimulated with exogenous VEGF, while it reduced migration and tube formation in untreated HRMECs. Taken together, our results demonstrate the antiangiogenic effects of AKBA in a model of pathologic neovascularization, providing a rationale for further investigation of AKBA as a promising therapeutic agent to reduce the impact of proliferative retinopathies.
Exp Eye Res. 2015 Jun;135():67-80.
PMID: 25913458 [PubMed - indexed for MEDLINE]
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| 18. |
Synthesis and structure-activity relationships of boswellic acid derivatives as potent VEGFR-2 inhibitors.
Shen S, Xu X, Liu Z, Liu J, Hu L
A series of AKBA derivatives were synthesized, and evaluated as potent VEGFR-2 inhibitors. The initial biological evaluation indicated that the introduction of C-24 amide group or a heterocycle at C-2,3 position effectively improved the potency. Further structure-activity relationship analysis showed that amide (7, 23, 25, and 26) and heterocycle (19, 34, and 36) substituted AKBA derivatives displayed more potential anti-proliferation activities than AKBA (1) on HUVECs that express high levels of VEGFR-2. Among all tested compounds, compounds 7 and 19 exhibited the best potency (IC₅₀: 2.36 and 2.13 μM) and obvious inhibitory activities with VEGFR-2 inhibition rates of 96% and 94% at 50 μM, respectively.
Bioorg Med Chem. 2015 May;23(9):1982-93.
PMID: 25819335 [PubMed - indexed for MEDLINE]
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| 19. |
Effects of the Four-Herb Compound ANBP on Wound Healing Promotion in Diabetic Mice.
Hou Q, He WJ, Chen L, Hao HJ, Liu JJ, Dong L, Tong C, Li MR, Zhou ZZ, Han WD, Fu XB
Wound healing is a troublesome problem in diabetic patients. Besides, there is also an increased risk of postsurgical wound complications for diabetic patient. It has been revealed that traditional Chinese medicine may promote healing and inhibit scar formation, while the changes of morphology and physiology of wounds on such medicine treatment still remain elusive. In this study, we first used the ultralow temperature preparation method to produce mixed superfine powder from Agrimonia pilosa (A), Nelumbo nucifera (N), Boswellia carteri (B), and Pollen typhae (P), named as ANBP. Applying ANBP on 40 streptozotocin (STZ)-induced diabetic C57BL/6 mice (4-6 weeks, 20 ± 2 g), we observed that the wound healing process was accelerated and the wound healing time was shortened (14 days, P < .05). Pathological observation using hematoxylin-eosin staining indicated that inflammatory cells were reduced (P < .05) while the thickness of granulation tissue and length of epithelial tongue were increased (P < .05). The vascular density was increased on 7 and 14 days after ANBP treatment. Masson and Sirius red staining showed that, at the early stage of trauma, the expressions of Col I and Col III, especially Col III, were increased in the ANBP group (P < .05). Studies in vitro demonstrated that tubular formation was significantly increased after ANBP treatment on human vascular endothelial cells in a dose-dependent way. Taken together, our studies revealed that ANBP treatment could accelerate wound healing, promote vascularization, and inhibit inflammation, suggesting the potential clinic application of ANBP for diabetes mellitus and refractory wounds.
Int J Low Extrem Wounds. 2015 Dec;14(4):335-42.
PMID: 25795279 [PubMed - indexed for MEDLINE]
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| 20. |
A computational and functional study elicits the ameliorating effect of the Chinese herbal formula Huo Luo Xiao Ling Dan on experimental ischemia-induced myocardial injury in rats via inhibition of apoptosis.
Han XD, Zhou ZW, Yang W, Ye HC, Xu YZ, Huang YF, Zhang T, Zhou SF
Ischemic heart disease (IHD) is the leading cause of death worldwide and remains a major life-threatening factor in humans. Apoptosis has been implicated in the pathogenesis of IHD. The Chinese herbal formula Huo Luo Xiao Ling Dan (HLXLD), one of the commonly used Chinese herbal formulas, consists of Salviae miltiorrhizae, Angelica sinensis, Gummi olibanum, and Commiphora myrrha, with a wide spectrum of pharmacological activity. However, the mechanism of action and molecular targets of HLXLD in the treatment of IHD are unclear. This study aimed to computationally predict the molecular interactions between the major active components of HLXLD and key regulators of apoptosis and then examine the effect of HLXLD on coronary artery ligation-induced acute myocardial ischemia in rats. The molecular interactions between the major active components of HLXLD, including ferulic acid, ligustilide, succinic acid, vanillic acid, tanshinone IIA, tanshinone IIB, danshensu, salvianolic acid A, salvianolic acid C, protocatechuic aldehyde, and β-boswellic acid and human protein molecules including B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 antagonist/killer 1 (Bak1), B cell lymphoma 2 (Bcl-2), procaspase 3, and caspase 9 with regard to hydrogen bond formation, charge interaction, and π-π stacking using Discovery Studio(®) program 3.1. The 12 HLXLD components were predicted by ADMET (absorption, distribution, metabolism, excretion and toxicity) Predictor to have favorable pharmacokinetic and low hepatotoxicity profiles. The acute myocardial ischemia was established by surgical ligation of the left anterior descending coronary artery. The rats were divided into a sham operative group, a model group, a positive control group treated with 0.2 mg/kg isosorbide mononitrate, and groups treated with 2.7, 5.4, or 10.8 g/kg HLXLD. The results showed that administration of HLXLD increased mean arterial pressure, left ventricular systolic pressure, heart rate, and maximal rate of rise/descent of left ventricular pressure levels. Administration of HLXLD significantly ameliorated coronary artery ligation-induced tissue damage in the left ventricle, with restored arrangement of myocardial fibers and recovered myoplasm in rats. Furthermore, HLXLD markedly increased the expression level of Bcl-2 but decreased the level of cleaved caspase 3. Taken together, administration of HLXLD attenuated acute myocardial ischemia-induced damage in cardiomyocytes and inhibited apoptotic death of cardiomyocytes, thereby exerting a cardioprotective effect in rats with IHD. These findings suggest that HLXLD may represent a promising herbal formula for the treatment of cardiovascular disease by counteracting apoptotic cell death via multiple active compounds. More studies are warranted to fully elucidate the mechanisms of action, identify the therapeutic targets, and validate the efficacy and safety of HLXLD in the treatment of IHD.
Drug Des Devel Ther. 2015;9():1063-102.
PMID: 25733819 [PubMed - indexed for MEDLINE]
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| 21. |
Cardioprotective and antioxidant effects of oleogum resin "Olibanum" from Bos Boswellia carteri Birdw. (Bursearceae).
Zaki AA, Hashish NE, Amer MA, Lahloub MF
One of the leading causes of death worldwide is cardiovascular disease, hence searching for a cure is an important endeavor. The totally safe, edible, and inexpensive Boswellia plant exudate, known as olibanum or frankincense, is considered to possess diverse medicinal values in traditional medicine and from recent biological studies. Investigating the cardioprotective and antioxidant activities of olibanum from a Boswellia species, family Bursearaceae, namely Boswellia carteri Birdw. was the aim of this study. Cardioprotective activity was evaluated using a model of myocardial infarction induced by isoprenaline (ISO), while antioxidant activity was tested adopting nitric oxide scavenging (NOS) and azino-bis-3-ethyl benzthiazoline-6-sulfonic acid (ABTS) assays. The results revealed a mild cardioprotective effect and weak antioxidant activity.
Chin J Nat Med. 2014 May;12(5):345-50.
PMID: 24856757 [PubMed - indexed for MEDLINE]
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| 22. |
Three pentacyclic triterpenes protect H9c2 cardiomyoblast cells against high-glucose-induced injury.
Chan CY, Mong MC, Liu WH, Huang CY, Yin MC
H9c2 cardiomyoblast cell line was used to examine the protection of three triterpenes, asiatic acid, boswellic acid, and oleanolic acid, at 5 or 10 μM against high-glucose-induced injury. High glucose stimulated reactive oxygen species (ROS), oxidized glutathione (GSSG), interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 production, as well as decreased glutathione peroxidase (GPX), glutathione reductase (GR) and catalase activities, and protein expression. However, pre-treatments of three triterpenes reserved glutathione, maintained activity and expression of GPX, GR, and catalase, as well as lowered ROS, GSSG, and inflammatory cytokines generation. High glucose reduced Na(+)-K(+)-ATPase activity, raised nuclear factor kappa (NF-κ) B and caspase-3 activities, up-regulated protein expression of NF-κB, mitogen-activated protein kinase, Bax, and cleaved caspase-3, as well as down-regulated Bcl-2 expression. Pre-treatments of three triterpenes retained Na(+)-K(+)-ATPase activity, declined NF-κB and caspase-3 activities, reserved Bcl-2 expression, as well as suppressed protein expression of NF-κB, p-p38, Bax, and cleaved caspase-3. These findings suggest that these triterpenes are potent cardiac-protective agents.
Free Radic Res. 2014 Apr;48(4):402-11.
PMID: 24393047 [PubMed - indexed for MEDLINE]
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| 23. |
Ethanolic extract of Boswellia ovalifoliolata bark and leaf attenuates doxorubicin-induced cardiotoxicity in mice.
Uma Mahesh B, Shrivastava S, Kuncha M, Sahu BD, Swamy CV, Pragada RR, Naidu VG, Sistla R
The aim of the study was to investigate the potential protective effect of ethanolic extract of Boswellia ovalifoliolata (BO) bark and leaf against doxorubicin (DOX)-induced cardiotoxicity in mice. Ethanolic extracts of BO bark (400 mg/kg) and leaves (250 mg/kg) were given orally to mice for 9 consecutive days and DOX (15 mg/kg; i.p.) was administered on the seventh day. Extract protected against DOX-induced ECG changes. It significantly inhibited DOX-provoked glutathione depletion and accumulation of malondialdehyde. The decrease in antioxidant enzyme activities of catalase, superoxide dismutase, glutathione peroxidase in cardiac tissue were significantly (p<0.05) mitigated after treatment with BO bark and leaf extracts. Pretreatment with BO significantly (p<0.05) restored the levels of DOX-induced rise of SGPT, SGOT, serum lactate dehydrogenase and creatine kinase-MB levels. These findings suggest that ethanolic extract of BO has protective effects against DOX-induced cardiotoxicity.
Environ Toxicol Pharmacol. 2013 Nov;36(3):840-9.
PMID: 23981374 [PubMed - indexed for MEDLINE]
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| 24. |
The selective 5-LOX inhibitor 11-keto-β-boswellic acid protects against myocardial ischemia reperfusion injury in rats: involvement of redox and inflammatory cascades.
Elshazly SM, Abd El Motteleb DM, Nassar NN
Myocardial ischemia induces 5-lipoxygenase (LOX) translocation and leukotriene production in the heart. Leukotrienes increase inflammatory responses aggravating, thereby, ischemia-reperfusion (I/R) injury. This study aimed to investigate whether the selective 5-LOX inhibitor 11-keto-β-boswellic acid (11-keto BA), in three different dose levels, exert a protective effect on myocardial I/R injury in an in vivo rat heart model. Sixty male Wister rats were used in this study and divided into five equal groups (n=12): GP1, sham-operated receiving normal saline; Gp 2, rats were subjected to 45 min left anterior descending coronary artery ligation followed by 4 h reperfusion to serve as I/R group. Gps 3-5 received 11-keto BA in doses 250, 500, 1,000 mg/kg, respectively, via an oral gavage for 7 days then were exposed to I/R. I/R injury induced a significant elevation in myeloperoxidase activity and gene expression of intracellular adhesion molecules, cyclooxygenase-2, 5-lipooxygenasae, nuclear factor kappa-beta, tumor necrosis factor alpha, nuclear factor (erythroid-derived 2)-like 2, and hemeoxygenease-1 consequently with reduction in glutathione peroxidase in heart tissues. Furthermore, immunohistochemical examination of the heart tissues showed positive immuostaining for both 3-nitrotyrosine and caspase-3 with DNA-ladder formation in all diseased rats. 11-keto BA in three dose levels exerted dose dependent cardioprotective effect manifested by dose-dependent reduction in serum lactate dehydrogenase and infract size through mechanisms related to enhancement of antioxidant capacity and prevention of inflammatory cascades.
Naunyn Schmiedebergs Arch Pharmacol. 2013 Sep;386(9):823-33.
PMID: 23771412 [PubMed - indexed for MEDLINE]
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| 25. |
Gum resin of Boswellia serrata inhibited human monocytic (THP-1) cell activation and platelet aggregation.
Kokkiripati PK, Bhakshu LM, Marri S, Padmasree K, Row AT, Raghavendra AS, Tetali SD
ETHNOPHARMACOLOGICAL RELEVANCE: Stem bark gum resin extract of Boswellia serrata is traditionally used in India for its hemostatic, antiinflammatory and cardiovascular health effects and it is named as Śallakī in Ayurvedic medicine.
AIM OF THE STUDY: This study was conducted to evaluate the antioxidative and antithrombotic properties of stem bark gum resin extracts of Boswellia serrata (BS).
MATERIALS AND METHODS: The inhibitory activity of the BSWE and BSAE on FeCl(3) induced lipid peroxidation (in vitro) in rat liver and heart homogenates was measured spectrophotometrically. Their effect on H(2)O(2) induced reactive oxygen species (ROS) generation in human monocytic (THP-1) cells was investigated by tracking intensity of a cell permeable fluorescent dye, H(2)DCFDA and subjecting the cell samples to confocal microscopy. Further, the effect of BSAE and BSWE on ADP-induced platelet aggregation was assessed using a multimode detection plate reader, plasma coagulation times using an automated blood coagulation analyzer and on human blood clotting factors Xa and XIa using chromogenic substrate. Phytomarker analysis of the water (BSWE) and hydroalcoholic (BSAE) extracts of BS-gum resin was done through HPLC using a standard compound AKβBA.
RESULTS: BSAE and BSWE inhibited, to varied extents, the lipid peroxidation in liver (80%) and heart (50%) tissue homogenates of male Wistar rats. Further, BSAE (30 μg dwt/mL) and BSWE (300 μg dwt/mL) attenuated ≥ 60% of H(2)O(2) mediated ROS generation in THP-1 cells. In case of standard compounds, ascorbate (20 μg dwt/mL) and butylated hydroxytoluene (BHT) (10 μg dwt/mL) completely scavenged ROS in the cells. BSAE and BSWE at 3 mg dwt/mL completely inhibited ADP induced platelet aggregation and activities were comparable to 20 μg/mL of heparin. The extracts also showed very high activity in prolonging coagulation time periods. Both types of extracts extended prothrombin time (PT) from ∼13 to >60s and activated partial thromboplastin time (APTT) from ∼32s to >90s. BSAE inhibited clotting factors Xa and XIa remarkably at 6 μg of dwt where as BSWE did not show much effect on FXa and showed 30% inhibition on FXIa at 120 μg. 10 μg of heparin was required to inhibit about 30% activity of the above factors. HPLC analyses suggested that BSAE and BSWE had AKβBA of 9% (w/w) and 7.8% (w/w) respectively.
CONCLUSION: Present study demonstrated antioxidant and antithrombotic anticoagulant activities of water and hydroalcoholic extracts of Boswellia serrata's gum resin. We suggest that BS-gum resin as a good source for lead/therapeutic compounds possessing antioxidant, antiplatelet and anticoagulant activities.
J Ethnopharmacol. 2011 Sep;137(1):893-901.
PMID: 21771654 [PubMed - indexed for MEDLINE]
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| 26. |
Olibanum extract inhibits vascular smooth muscle cell migration and proliferation in response to platelet-derived growth factor.
Choi OB, Park JH, Lee YJ, Lee CK, Won KJ, Kim J, Lee HM, Kim B
Olibanum (Boswellia serrata) has been shown to have anti-inflammatory, anti-arthritic and anti-cancer effects. This study determined the role of a water extract of olibanum in platelet-derived growth factor (PDGF)-stimulated proliferation and migration of rat aortic smooth muscle cells (RASMCs). PDGF-BB induced the migration and proliferation of RASMCs that were inhibited by olibanum extract in a dose-dependent manner. The PDGF-BB-increased phosphorylation of p38 mitogen-activated protein kinase (MAPK); the heat shock protein (Hsp) 27 was significantly inhibited by the olibanum extract. The effects of PDGF-BB-induced extracellular signal-regulated kinase1/2 was not altered by the olibanum extract. Treatment with olibanum extract inhibited PDGF-BB-stimulated sprout out growth of aortic rings. These results suggest that the water extract of olibanum inhibits PDGF-BB-stimulated migration and proliferation in RASMCs as well as sprout out growth, which may be mediated by the inhibition of the p38 MAPK and Hsp27 pathways.
Korean J Physiol Pharmacol. 2009 Apr;13(2):107-13.
PMID: 19885005 [PubMed - as supplied by publisher]
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| 27. |
Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis.
Pang X, Yi Z, Zhang X, Sung B, Qu W, Lian X, Aggarwal BB, Liu M
The role of angiogenesis in tumor growth and metastasis is well established. Identification of a small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we showed that acetyl-11-keto-beta-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBA) after solid tumors reached approximately 100 mm(3) (n = 5). The inhibitory effect of AKBA on tumor growth was well correlated with suppression of angiogenesis. When examined for the molecular mechanism, we found that AKBA significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively suppressed vascular endothelial growth factor (VEGF)-induced microvessel sprouting in rat aortic ring assay ex vivo. Furthermore, AKBA inhibited VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures from primary cultured human umbilical vascular endothelial cells in a dose-dependent manner. Western blot analysis and in vitro kinase assay revealed that AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2) kinase (KDR/Flk-1) with IC(50) of 1.68 micromol/L. Specifically, AKBA suppressed the downstream protein kinases of VEGFR2, including Src family kinase, focal adhesion kinase, extracellular signal-related kinase, AKT, mammalian target of rapamycin, and ribosomal protein S6 kinase. Our findings suggest that AKBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signaling pathways.
Cancer Res. 2009 Jul;69(14):5893-900.
PMID: 19567671 [PubMed - indexed for MEDLINE]
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| 28. |
Stilbene glycosides are natural product inhibitors of FGF-2-induced angiogenesis.
Hussain S, Slevin M, Ahmed N, West D, Choudhary MI, Naz H, Gaffney J
BACKGROUND: Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with pathological processes, in particular tumour development, and is a target for the development of new therapies. We have investigated the anti-angiogenic potential of two naturally occurring stilbene glycosides (compounds 1 and 2) isolated from the medicinal plant Boswellia papyriferai using large and smallvessel-derived endothelial cells. Compound 1 (trans-4',5'-dihydroxy-3-methoxystilbene-5-O-{alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)}-beta-D-glucopyranoside was the more hydrophilic and inhibited FGF-2-induced proliferation, wound healing, invasion in Matrigel, tube formation and angiogenesis in large and small vessel-derived endothelial cells and also in the chick chorioallantoic membrane assay. Using a binding assay we were able to show compound 1 reduced binding of FGF-2 to fibroblast growth factor receptors-1 and -2. In all cases the concentration of compound 1 which caused 50% inhibition (IC50) was determined. The effect of compound 1 on EGF and VEGF-induced proliferation was also investigated.
RESULTS: Compound 1 inhibited all stages of FGF-2 induced angiogenesis with IC50 values in the range 5.8 +/- 0.18 - 48.90 +/- 0.40 microM but did not inhibit EGF or VEGF-induced angiogenesis. It also inhibited FGF-2 binding to FGF receptor-1 and -2 with IC50 values of 5.37 +/- 1.04 and 9.32 +/- 0.082 muM respectively and with concommotant down-regulation of phosphorylated-ERK-1/-2 expression. Compound 2 was an ineffective inhibitor of angiogenesis despite its structural homology to compound 1.
CONCLUSION: Compound 1 inhibited FGF-2 induced angiogenesis by binding to its cognate receptors and is an addition to the small number of natural product inhibitors of angiogenesis.
BMC Cell Biol. 2009 Apr;10():30.
PMID: 19389252 [PubMed - indexed for MEDLINE]
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| 29. |
BHUx: a patented polyherbal formulation to prevent hyperlipidemia and atherosclerosis.
Tripathi YB
Since hyperlipidemia, inflammation and obesity are closely related to atherosclerosis, therefore management of these factors together would be beneficial for overall treatment approach for atherosclerosis. Although, Indian system of medicine, especially Ayurveda has several medicinal plants with proven beneficial claims towards these pathological conditions, but most of them lack enough experimental data. BHUx is a novel polyherbal formulation, consisting of 5 medicinal plants namely Termenalia arjuna, Strychnox nux vomica, Boswellia serrata, Commiphora mukul, and Semecarpus anacardium, which have history of clinical use as single or in other combinations, but these plant fractions were never tried collectively in this ratio as in BHUx, which has been found to be effective on all the etiological factors, together. In this paper, antioxidant, anti-inflammatory, hypo-lipidemic, anti-proliferative properties of BHUx have been studied on several experimental models based on chemical tests, cell culture, in vitro models, and in vivo experiments with normal and transgenic animals. A separate pre-clinical toxicity study has also been carried out to prove its safety margin in therapeutic doses. Further, clinical trail of BHUx is under way, before it comes to market for public use as functional food to maintain healthy heart. This article also review some patent related to the field.
Recent Pat Inflamm Allergy Drug Discov. 2009 Jan;3(1):49-57.
PMID: 19149746 [PubMed - indexed for MEDLINE]
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| 30. |
Thrombin-induced expression of endothelial CX3CL1 potentiates monocyte CCL2 production and transendothelial migration.
Popovic M, Laumonnier Y, Burysek L, Syrovets T, Simmet T
CX3CL1 (fractalkine, neurotactin) is the sole CX3C chemokine. It induces monocyte locomotion in its cleaved form, but in its membrane-anchored form, it also acts as an adhesion molecule. The expression of CX3CL1 is up-regulated in endothelial cells by proinflammatory cytokines such as IL-1 or TNF-alpha. Here, we studied the effect of the serine protease thrombin on endothelial CX3CL1 induction and its putative relevance for monocyte function. In HUVEC, thrombin triggered a time- and concentration-dependent expression of CX3CL1 at the mRNA and the protein level as shown by RT-PCR, Western immunoblotting, and flow cytometric analysis. Thrombin induced CX3CL1 by activating protease-activated receptor 1 (PAR1) as demonstrated by the use of PAR1-activating peptide and the PAR1-specific antagonist SCH 79797. The thrombin-induced CX3CL1 expression was NF-kappaB-dependent, as shown by EMSA, ELISA, and by inhibition of the NF-kappaB signaling pathway by the IkappaB kinase inhibitor acety-11-keto-beta-boswellic acid or by transient overexpression of a transdominant-negative form of IkappaBalpha. Upon cocultivation of human monocytes with HUVEC, the thrombin-dependent induction of membrane-anchored CX3CL1 in HUVEC triggered monocyte adhesion and an enhanced release of the MCP-1/CCL2 by monocytes and potentiated the monocyte transendothelial migration. Accordingly, the recombinant extracellular domain of CX3CL1 induced CCL2 release by monocytes. Thus, the thrombin-induced monocyte/endothelial cell cross-talk mediated by increased CX3CL1 expression potentiates the CCL2 chemokine generation that might contribute to the recruitment of monocytes into inflamed areas.
J Leukoc Biol. 2008 Jul;84(1):215-23.
PMID: 18436581 [PubMed - indexed for MEDLINE]
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| 31. |
Antiinflammatory and antiatherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-beta-boswellic acid in LPS-challenged ApoE-/- mice.
Cuaz-Pérolin C, Billiet L, Baugé E, Copin C, Scott-Algara D, Genze F, Büchele B, Syrovets T, Simmet T, Rouis M
OBJECTIVE: In this article, we studied the effect of acetyl-11-keto-beta-boswellic acid (AKbetaBA), a natural inhibitor of the proinflammatory transcription factor NF-kappaB on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE-/-) mice.
METHODS AND RESULTS: Atherosclerotic lesions were induced by weekly LPS injection in apoE-/- mice. LPS alone increased atherosclerotic lesion size by approximately 100%, and treatment with AKbetaBA significantly reduced it by approximately 50%. Moreover, the activity of NF-kappaB was also reduced in the atherosclerotic plaques of LPS-injected apoE-/- mice treated with AKbetaBA. As a consequence, AKbetaBA treatment led to a significant downregulation of several NF-kappaB-dependent genes such as MCP-1, MCP-3, IL-1alpha, MIP-2, VEGF, and TF. By contrast, AKbetaBA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocyte-derived cytokines. Moreover, AKbetaBA potently inhibited the IkappaB kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of IkappaB alpha and inhibition of p65/NF-kappaB activation. Comparable AKbetaBA-mediated inhibition was also observed in LPS-stimulated human macrophages.
CONCLUSIONS: The inhibition of NF-kappaB activity by plant resins from species of the Boswellia family might represent an alternative for classical medicine treatments for chronic inflammatory diseases such as atherosclerosis.
Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):272-7.
PMID: 18032778 [PubMed - indexed for MEDLINE]
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| 32. |
Induction of central signalling pathways and select functional effects in human platelets by beta-boswellic acid.
Poeckel D, Tausch L, Altmann A, Feisst C, Klinkhardt U, Graff J, Harder S, Werz O
We have recently shown that in polymorphonuclear leukocytes, 11-keto boswellic acids (KBAs) induce Ca2+ mobilisation and activation of mitogen-activated protein kinases (MAPK). Here we addressed the effects of BAs on central signalling pathways in human platelets and on various platelet functions. We found that beta-BA (10 microM), the 11-methylene analogue of KBA, caused a pronounced mobilisation of Ca2+ from internal stores and induced the phosphorylation of p38 MAPK, extracellular signal-regulated kinase (ERK)2, and Akt. These effects of beta-BA were concentration dependent, and the magnitude of the responses was comparable to those obtained after platelet stimulation with thrombin or collagen. Based on inhibitor studies, beta-BA triggers Ca2+ mobilisation via the phospholipase (PL)C/inositol-1,4,5-trisphosphate pathway, and involves Src family kinase signalling. Investigation of platelet functions revealed that beta-BA (> or =10 microM) strongly stimulates the platelet-induced generation of thrombin in an ex-vivo in-vitro model, the liberation of arachidonic acid (AA), and induces platelet aggregation in a Ca2+-dependent manner. In contrast to beta-BA, the 11-keto-BAs (KBA or AKBA) evoke only moderate Ca2+ mobilisation and activate p38 MAPK, but fail to induce phosphorylation of ERK2 or Akt, and do not cause aggregation or significant generation of thrombin. In summary, beta-BA potently induces Ca2+ mobilisation as well as the activation of pivotal protein kinases, and elicits functional platelet responses such as thrombin generation, liberation of AA, and aggregation.
Br J Pharmacol. 2005 Oct;146(4):514-24.
PMID: 16086030 [PubMed - indexed for MEDLINE]
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| 33. |
Anti-inflammatory properties of BHUx, a polyherbal formulation to prevent atherosclerosis.
Tripathi YB, Reddy MM, Pandey RS, Subhashini J, Tiwari OP, Singh BK, Reddanna P
BHUx is a polyherbal formulation consisting of water-soluble fractions of five medicinal plants (Commiphora mukul, Terminalia arjuna, Boswellia serrata, Semecarpus anacardium and Strychnos nux vomica). The present study was undertaken to evaluate its antioxidant and antiinflammatory effects. BHUx, standardized by HPLC fingerprinting and filtered through 0.2 microm filter paper, was employed for different studies under in vivo and in vitro conditions. Under in vivo conditions, BHUx significantly reduced inflammation in the carrageenan-induced rat paw oedema model of inflammation, suggesting its anti-inflammatory properties. In order to test the mechanism of action of BHUx, further in vitro studies were undertaken on cumene-hydroperoxide-induced lipid peroxidation (CHP) in liver homogenate, LPS-induced NO production in peritoneal macrophages and on key enzymes of arachidonic acid cascade, involved in the mediation of inflammation. Under the conditions, BHUx showed concentration-dependent inhibition of CHP-induced lipid peroxidation in liver homogenate, suggesting its antioxidant properties. Similarly the potent anti-inflammatory effects of BHUx are evident by (a) preferential inhibition of COX-2 (IC50 for COX-2 = 80 microg/ml and IC50 for COX-1 = 169 microg/ml), (b) low ratios in the IC50 values of COX-2/COX-1 (0.47), (c) decreased production of NO in LPS-induced peritoneal macrophages and (d) inhibition of 5-LOX (IC50 = 795 microg/ml). BHUx also showed a preference for inhibiting 15-lipoxygenase (IC50 = 44 microg/ml), a key enzyme implicated in LDL oxidation. These studies suggest that BHUx is acting mainly at three levels, i.e., as a potent natural antioxidant, by reduction of key inflammatory mediators of arachidonic acid cascade and by preventing 15-LOX-mediated LDL oxidations, to prevent atherosclerosis.
Inflammopharmacology. 2004;12(2):131-52.
PMID: 15265316 [PubMed - indexed for MEDLINE]
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