Bile acids (BAs), the end-products of cholesterol catabolism, are signaling molecules activating several cellular networks through the recognition of nuclear and membrane receptors, such as FXR (farnesoid-X-receptor) and GP-BAR1. BAR502 is a dual FXR and GP-BAR1 agonist with EC50 values of 2 and 0.4 μM, respectively. BAR502 (10 μM) was able to induce the expression of pro-glucagon mRNA in GLUTAg cells, an intestinal endocrine cell line, as well as to increase cAMP concentrations in THP-1 cells[3]. In C57BL6 mice, BAR502 (15 mg/kg/day) reversed the NASH (non-alcoholic steatohepatitis)-like features induced by high fat diet (HFD). In addition, BAR502 reduced liver fibrosis scores by 70% and expression of pro-fibrogenetic genes (αSMA and α1-collagen), as well as the inflammatory score and liver expression of F4/80, IL-1β, IL-6, MCP-1, RANTES and TNFα mRNA[4].
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