Treatment with a polyherbal extract improves fat metabolism, attenuates hepatic stellate cell activation and fibrogenesis

ABSTRACT Non-alcoholic steatohepatitis (NASH) involves dysregulations in denovo lipogenesis, fatty acid oxidation, and fibrogenesis. Targeting these pathways holds promise for the treatment of liver disorders. Here we test the extract of a polyherbal formulation (namely Liv.52), which is approved by the Government of India’s Drug Regulatory Authority - AYUSH. The current study evaluates the effect of Liv.52 on denovo lipogenesis, fatty acid oxidation, and fibrogenesis. Both in vivo and in vitro model systems were employed to evaluate the efficacy of this polyherbal formulation. Male Wistar rats were dosed with Liv.52 for 2 weeks (250mg/k.g) and expression levels of the genes involved in de novo lipogenesis and fatty acid oxidation pathways were analysed by quantitative real time PCR. Liv.52 treatment resulted in increased hepatic fatty acid oxidation and decreased de novo lipogenesis in these rats. It also reduced hepatic stellate cell activation in CCL 4 treated Wistar rats as evidenced by histological evaluation. For in vitro experiments, HepG2 cells were cultured under lipotoxic conditions (using 200μM palmitic acid) and the conditioned media from these cells were used for inducing activation and fibrogenesis in human hepatic stellate cells (HHSteC). Treatment with lipotoxic conditioned media resulted in activation of hepatic stellate cells and fibrogenesis, as evidenced by increased expression of α-smooth muscle actin (α-SMA), and desmin (markers of stellate cell activation) and increased levels of collagen and lumican (markers of fibrogenesis). Treatment with Liv.52 reversed the up-regulation of α-SMA, collagen and lumican levels in HHSteC cells. These results indicate that Liv.52 exerts its hepatoprotective effect by improving fatty acid metabolism and fibrogenesis.