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Menebar Ilmu Pengetahuan

Sanguinarine, suatu inhibitor poten aktivasi NF-kB

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Sanguinarin atau (Pseudochelerythrine) diturunkan dari akar Sanguinaria canadensis and other poppy-fumaria species. This benzophenanthridine alkaloid is a structural homologue of chelerythrine, which is a potent inhibitor of protein kinase C. Sanguinarine has been shown to display antitumor (3) and anti-inflammatory properties in animals (4) and to inhibit neutrophil function, including degranulation and phagocytosis in vitro(5). It is also a potent inhibitor of Na-K-dependent ATPase and cholinesterase .

NF-κB is a nuclear transcription factor that resides in its inactive state in the cytoplasm as a heterotrimer consisting of p50, p65, and IκBα subunits. On activation of the complex, IκBα sequentially undergoes phosphorylation, ubiquinitation, and degradation, thus releasing the p50-p65 heterodimer for translocation to the nucleus . Treatment of cells with various inflammatory and stress stimuli including lipopolysaccharide, tumor necrosis factor (TNF),1 interleukin (IL)-1, ceramide, hydrogen peroxides, ultraviolet light, phorbol myristate acetate (PMA), and okadaic acid (OA) activates the transcription factor. NF-κB is a ubiquitous transcription factor that regulates the expression of various cytokines, their receptors, major histocompatibility complex genes, cell adhesion proteins, and other gene products involved in inflammation, septic shock, atherosclerosis, cell proliferation, and viral replication including human immunodeficiency virus-1.

Sanguinarine exhibits antimicrobial, anti-inflammatory, and antioxidant properties. Since anti-inflammatory compounds like aspirin and glucocorticoid have been shown to inhibit activation of NF-κB, we investigated the effect of sanguinarine on activation of NF-κB induced by a wide variety of agents including TNF. The results show that sanguinarine is a potent inhibitor of NF-κB activation that blocks the phosphorylation and degradation of IκBα, thus suggesting that sanguinarine is a potential candidate for intervening in NF-κB-dependent pathological responses.


Chaturvedi MM, Kumar A, Darnay BG, Chainy GB, Agarwal S, Aggarwal BB., Sanguinarine (pseudochelerythrine) is a potent inhibitor of NF-kappaB activation, IkappaBalpha phosphorylation, and degradation, J Biol Chem. 1997 Nov 28;272(48):30129-34.[link]


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menebar ilmu pengetahuan

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