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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

Betulinic acid exerts anti-hepatitis C virus activity via the suppression of NF-κB- and MAPK-ERK1/2-mediated COX-2 expression.

Abstract Source:

Br J Pharmacol. 2015 Jun 23. Epub 2015 Jun 23. PMID: 26102077

Abstract Author(s):

Chun-Kuang Lin, Chin-Kai Tseng, Kai-Hsun Chen, Shih-Hsiung Wu, Chih-Chuang Liaw, Jin-Ching Lee

Article Affiliation:

Chun-Kuang Lin

Abstract:

BACKGROUND AND PURPOSE: This study was designed to evaluate the effect of betulinic acid (BA), extracted from Avicennia marina, on the replication of hepatitis C virus (HCV) and to investigate the mechanism of this BA-mediated anti-HCV activity.

EXPERIMENTAL APPROACH: HCV replicon and infectious systems were used to evaluate the anti-HCV activity of BA. Exogenous COX-2 or knock-down of COX-2 expression was used to investigate the role of COX-2 in the anti-HCV activity of BA. The effects of BA on the phosphorylation of NF-κB and on kinases in the MAPK signalling pathway were determined. The anti-HCV activity of BA in combination with other HCV inhibitors was also determined to assess its use as an anti-HCV supplement.

KEY RESULTS: BA inhibited HCV replication in both Ava5 replicon cells and in a cell culture-derived infectious HCV particle system. Treatment with a combination of BA and IFN-α, the protease inhibitor telaprevir or the NS5B polymerase inhibitor sofosbuvir resulted in the synergistic suppression of HCV RNA replication. Exogenous overexpression of COX-2 gradually attenuated the inhibitory effect of BA on HCV replication, suggesting that BA reduces HCV replication by suppressing the expression of COX-2. In particular, BA down-regulated HCV-induced COX-2 expression by reducing the phosphorylation of NF-κB and ERK1/2 of the MAPK signalling pathway.

CONCLUSIONS AND IMPLICATIONS: BA inhibits HCV replication by suppressing the NF-κB- and ERK1/2-mediated COX-2 pathway and may serve as a promising compound for drug development or as a potential supplement for use in the treatment of HCV-infected patients.

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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