Protection by boswellic acids against galactosamine/endotoxin-induced hepatitis in mice

Safayhi, H.; Mack, T.; Ammon, H. P. T.

doi:10.1016/0006-2952(91)90575-p

Cited by 41 publications

(14 citation statements)

References 4 publications

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“…Boswellic acids are inhibitors of 5-lipoxygenase, and the inhibitory effect has been demonstrated in both intact cells and in the cell-free system (3,5,34). It was reported that MK886, the inhibitor of 5-lipoxygenase activating protein triggered apoptosis in both prostate and breast cancer cells (35,36).…”

Section: Discussionmentioning

confidence: 99%

Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells

Liu¹

2002

Carcinogenesis

172

125

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Boswellic acids are the effective components of gum resin of Boswellia serrata, which has anti-inflammatory properties. Recent studies on brain tumors and leukemic cells indicate that boswellic acids may have antiproliferative and apoptotic effects with the mechanisms being not studied in detail. We studied their antiproliferative and apoptotic effects on colon cancer cells and the pathway leading to apoptosis. HT-29 cells were treated with β-boswellic acid (BA), keto-β-boswellic acid (K-BA) and acetyl-keto-β-boswellic acid (AK-BA), respectively. Apoptosis was determined by flow cytometry, by cytoplasmic DNA-histone complex and the activity of caspase-3. The cleavage of poly-(ADP-ribose)-polymerase (PARP) and expression of Fas were examined by western blot. Specific caspase inhibitors, polyclonal Fas antibody, and antagonistic Fas antibody ZB4 were employed to elucidate apoptotic pathways. DNA synthesis and cell viability were examined. Both K-BA and AK-BA increased cytoplasmic DNA-histone complex dose-dependently and increased pre-G 1 peak in flow cytometer analysis, with the effects of AK-BA being stronger than K-BA. BA only increased the formation of DNA-histone complex at a high concentration. K-BA and AK-BA increased caspase-8, caspase-9 and caspase-3 activities accompanied by cleavage of PARP. The effects of AK-BA on formation of cytoplasmic DNA histone and on caspase-3 activation were 3.7-and 3.4-fold, respectively, more effective than those induced by camptothecin. The apoptosis induced by AK-BA was inhibited completely by caspase-3 or caspase-8 inhibitor and partially by caspase-9 inhibitor. ZB4 blocked exogenous Fas ligand-induced apoptosis, but had no effect on AK-BA-induced apoptosis. AK-BA had no significant effect on expression of Fas. Apart from apoptotic effect, these acids also inhibited [ 3 H]thymidine incorporation and cell viability to different extent. In conclusion, boswellic acids, particularly AK-BA and K-BA have antiproliferative and apoptotic effects in human HT-29 cells. The apoptotic effect is mediated via a pathway dependent on caspase-8 activation but independent of Fas/FasL interaction.

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Section: Discussionmentioning

confidence: 99%

Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells

Liu¹

2002

Carcinogenesis

172

125

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“…It was first observed that BAs protect against galactosamine/endotoxin-induced hepatitis in mice [22]. Later, it was found that high-dose B. serrata extract as well as both low-and high-dose AKBA significantly attenuated tissue injury scores in Sprague-Dawley rats after subcutaneous injections of indomethacin, and significantly reduced macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration as a model of experimental ileitis [23].…”

Section: Inflammatory Bowel Diseasementioning

confidence: 98%

Boswellic Acids: Biological Actions and Molecular Targets

Poeckel¹,

Werz

2006

CMC

203

153

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Gum resin extracts of Boswellia species have been traditionally applied in folk medicine for centuries to treat various chronic inflammatory diseases, and experimental data from animal models and studies with human subjects confirmed the potential of B. spec extracts for the treatment of not only inflammation but also of cancer. Analysis of the ingredients of these extracts revealed that the pentacyclic triterpenes boswellic acids (BAs) possess biological activities and appear to be responsible for the respective pharmacological actions. Approaches in order to elucidate the molecular mechanisms underlying the biological effects of BAs identified 5-lipoxygenase, human leukocyte elastase, toposiomerase I and II, as well as IkappaB kinases as molecular targets of BAs. Moreover, it was shown that depending on the cell type and the structure of the BAs, the compounds differentially interfere with signal transduction pathways including Ca(2+/-) and MAPK signaling in various blood cells, related to functional cellular processes important for inflammatory reactions and tumor growth. This review summarizes the biological actions of BAs on the cellular and molecular level and attempts to put the data into perspective of the beneficial effects manifested in animal studies and trials with human subjects related to inflammation and cancer.

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“…In experimental animal models of inflammation, BA has been shown to be effective against Crohn's disease, ulcerative colitis, and ileitis (10 -12), adjuvant or BSA-induced arthritis (13,14), galactosamine/endotoxin-induced hepatitis in mice (15), and osteoarthritis (16). Besides having anti-inflammatory effects, BA also exhibits antitumor effects as indicated by its activity against brain tumors (17,18), leukemic cells (19,20), colon cancer cells (21), metastatic melanoma and fibrosarcoma cells (22), and hepatoma (23).…”

mentioning

confidence: 99%

Acetyl-11-Keto-β-Boswellic Acid Potentiates Apoptosis, Inhibits Invasion, and Abolishes Osteoclastogenesis by Suppressing NF-κB and NF-κB-Regulated Gene Expression

Takada

Ichikawa

Badmaev

et al. 2006

The Journal of Immunology

195

129

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Acetyl-11-keto-β-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-κB ligand-induced osteoclastogenesis, all of which are known to require NF-κB activation. These observations corresponded with the down-regulation of the expression of NF-κB-regulated antiapoptotic, proliferative, and angiogenic gene products. As examined by DNA binding, AKBA suppressed both inducible and constitutive NF-κB activation in tumor cells. It also abrogated NF-κB activation induced by TNF, IL-1β, okadaic acid, doxorubicin, LPS, H2O2, PMA, and cigarette smoke. AKBA did not directly affect the binding of NF-κB to the DNA but inhibited sequentially the TNF-induced activation of IκBα kinase (IKK), IκBα phosphorylation, IκBα ubiquitination, IκBα 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-κB-dependent reporter gene expression activated by TNFR type 1, TNFR-associated death domain protein, TNFR-associated factor 2, NF-κB-inducing kinase, and IKK, but not that activated by the p65 subunit of NF-κB. Overall, our results indicated that AKBA enhances apoptosis induced by cytokines and chemotherapeutic agents, inhibits invasion, and suppresses osteoclastogenesis through inhibition of NF-κB-regulated gene expression.

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Protection by boswellic acids against galactosamine/endotoxin-induced hepatitis in mice

Cited by 41 publications

References 4 publications

Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells

Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells

Boswellic Acids: Biological Actions and Molecular Targets

Acetyl-11-Keto-β-Boswellic Acid Potentiates Apoptosis, Inhibits Invasion, and Abolishes Osteoclastogenesis by Suppressing NF-κB and NF-κB-Regulated Gene Expression

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