Fig. 4.
Pheophytin Sorafenib Tosylate and IFNα-2a elicit synergistic inhibitory effect on HCV gene expression. (A) Typical isobologram for analyzing the interaction between two drugs. (B) The isobologram for the combined uses of pheophytin a and IFNα-2a. Luciferase-based replicon cell assays were performed under the indicated treatments. The fixed ratios adjusted by the IC50 (FICs) at 50% inhibition were calculated and the FICs for pheophytin a and IFNα-2a were plotted on the X-axis and Y-axis, respectively.
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Discussion
The global prevalence of HCV infection averages 3% according to the estimation made by the World Health Organization. Through bioactivity-guided screening, structure–activity relationship, and biochemical analysis, we report herein that HCV-NS3 is a potent molecular target of L. hypoglauca-derived pheophytin a. As a result, the viral proteins and RNA expression and the HCV infectivity are diminished. Notably, concomitant treatment of HCV replicon cells with pheophytin a and INFα-2a elicits synergistic effect and enhances anti-HCV activity without compensation of cell survival. This study thereby offers insight to the molecular basis for the anti-HCV activity of L. hypoglauca and indicates pheophytin a as a potent adjuvant regimen for INFα-2a therapy in the clinical setting.
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Conversely the concentrations of copper in the liver
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