ABSTRACT:
Liver fibrosis results due to excessive accumulation of extracellular matrix proteins including collagen. It is a complex process involving various cell types of liver including hepatocytes, several immune cell types and stellate cells. Current strategies for the treatment of liver fibrosis have shifted from single target approach to multi target approach and plant extracts contain several bioactive molecules which act on multiple pathways. In view of this, Liv.52 is one of the polyherbal formulations known worldwide for its beneficial effects against liver ailments. In the present study, we have evaluated the molecular mechanism of action of this polyherbal formula in an in vitro set up that captures metabolic overload, inflammation and stellate cell activation. HepG2 (Human, liver hepatoma) cells were exposed to palmitate and CCL, (carbon tetrachloride) for 24 hours to induce lipotoxic inflammation following which the conditioned media was used to induce stellate cell activation in HHSTEC (Human Hepatic Stellate) cell line. The effect of Liv52 on lipotoxicity and inflammation induced stellate cell activation was evaluated. Liv.52 showed 14.8522.47% protection against lipotoxicity and attenuated the expression of key markers of stellate cell activation viz. ACTA2 and Desmin and significantly reduced the levels of ECM (extra cellular matrix) proteins accumulation as measured by expression levels of lumican and cellular collagen content. Thus, the results indicate that Liv.52 efficiently counters the effects of metabolic overload and inflammation induced liver injury and halts the stellate cell activation, a central event in the process of progression of liver fibrosis.