A critical review on anti-fibrotic phytochemicals targeting activated hepatic stellate cells

Liver fibrosis is a major health concern occurring worldwide. It arises due to prolonged wound healing response of various insults like viral, autoimmune, cholestatic, drug-induced, and metabolic diseases. Currently, there is no clinically approved drug for liver fibrosis treatment. Hepatic stellate cells are the principal liver cells that are activated during liver fibrosis, and targeting these activated cells is an ideal therapeutic strategy. Numerous phytochemicals have been demonstrated in vitro and in vivo treating experimental liver fibrosis; however, none of them have been clinically approved for therapeutic use. This review mainly focuses on such hepatoprotective phytochemicals reported inhibiting major signaling pathways that are dysregulated in activated hepatic stellate cells. PRACTICAL APPLICATIONS: Liver fibrosis is a global health concern and there is no FDA approved drug to treat liver fibrosis. Although notable pharmacological agents like pentoxifylline, gliotoxin, imatinibmesylate, Gleevec, and so on are reported to exhibit anti-fibrotic effect, the major concern is their side effect. Hence, phytochemicals are promising candidates that could be employed against liver fibrosis. In this review, the anti-fibrotic potential of phytochemicals targeting activated HSCs are summarized. Understanding these phytochemicals will further help in the development of agents that are more effective against liver fibrosis.