Anticomplementary activity of Boswellic acids — An inhibitor of C3-convertase of the classical complement pathway

Kapil, A.; Moza, Nalini

doi:10.1016/0192-0561(92)90048-p

Cited by 56 publications

(29 citation statements)

References 15 publications

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“…Syringin (TC-4) and cordiol (TC-7), derived from an Indian plant, also have anticomplementary and immunomodulatory activities. Recently, it was discovered that these two compounds inhibit the C3 convertase of the classical complement pathway [89,90]. Recently Holmquist et al discovered Sushi domain-containing protein 4 (SUSD4) is a novel complement inhibitor and it inhibited the formation of the classical C3 convertase by 90% [91].…”

Section: Roles Of Complement Activation In Alzheimer’s Diseasementioning

confidence: 99%

What does complement do in Alzheimer’s disease? Old molecules with new insights

Shen

Yang

2013

Transl Neurodegener

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Increasing evidence suggests that inflammatory and immune components in brain are important in Alzheimer’s disease (AD) and anti-inflammatory and immunotherapeutic approaches may be amenable to AD treatment. It is known that complement activation occurs in the brain of patients with AD, and contributes to a local inflammatory state development which is correlated with cognitive impairment. In addition to the complement’s critical role in the innate immune system recognizing and killing, or targeting for destruction, complement proteins can also interact with cell surface receptors to promote a local inflammatory response and contributes to the protection and healing of the host. On the other hand, complement activation also causes inflammation and cell damage as an essential immune function to eliminate cell debris and potentially toxic protein aggregates. It is the balance of these seemingly competing events that influences the ultimate state of neuronal function. Our mini review will be focusing on the unique molecular interactions happening in the AD development, the functional outcomes of those interactions, as well as the contribution of each element to AD.

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Section: Roles Of Complement Activation In Alzheimer’s Diseasementioning

confidence: 99%

What does complement do in Alzheimer’s disease? Old molecules with new insights

Shen

Yang

2013

Transl Neurodegener

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“…Nowadays, boswellic acids have been regarded as specific, non-redox inhibitors of 5-lipoxygenase as they do not affect 12-lipoxygenase and cyclooxygenase (COX) activities (3)(4)(5). In addition, boswellic acids also inhibit leukocyte elastase, which may also contribute to their anti-inflammatory properties (6,7).…”

Section: Introductionmentioning

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

173

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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“…The traditional therapeutic usefulness of BA is the result of its anti-inflammatory activity, possibly mediated through the inhibition of 5-lipoxygenase (5-7) and leukocyte elastase (8,9). 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).…”

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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

196

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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Anticomplementary activity of Boswellic acids — An inhibitor of C3-convertase of the classical complement pathway

Cited by 56 publications

References 15 publications

What does complement do in Alzheimer’s disease? Old molecules with new insights

What does complement do in Alzheimer’s disease? Old molecules with new insights

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

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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