Hepatic steatosis is a metabolic disorder characterized by excessive accumulation of lipid in the liver. The activation of autophagy shows a promising effect in the elimination of intracellular lipids, potentially improving steatosis. Polygoni Cuspidati Rhizoma et Radix (PCRR) has been used for thousands of years in treating atherosclerosis, hepatitis, and gallstone disease. We recently found that PCRR exerts a potent anti-hepatic steatosis effect, but the active compounds responsible for its effect and underlying mechanism remain unknown. This study aims to investigate whether PCRR water extract intervention improves steatosis by regulating hepatic autophagic flux. We demonstrated that PCRR water extract promoted autophagic flux, enhanced lysosomal biogenesis, and alleviated steatosis in hepatocytes and in the livers of rats with steatosis through autophagy induction. Mechanistic investigation revealed that PCRR water extract inhibited the activity of MTORC1, thereby dephosphorylating and hence inducing nuclear translocation of the lipophagy inducer TFEB. Notably, knockdown of TFEB attenuated the promoting effects of PCRR on lipophagy in hepatocytes. Furthermore, blockage of autophagy by chloroquine inhibited the therapeutic effect of PCRR against hepatic steatosis in HFD-fed rats. Our findings demonstrate the potential of PCRR water extract as a novel autophagy enhancer for treating hepatic steatosis.
Keywords: Polygoni Cuspidati Rhizoma et Radix extract; Steatosis; TFEB; autophagy.
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