The phytochemical polydatin ameliorates non‐alcoholic steatohepatitis by restoring lysosomal function and autophagic flux

• DOI: 10.1111/jcmm.14320
• Publication Date: 2019-04-12T02:27:53Z
• Authors: Xiaoting Chen; Hung Chan; Lin Zhang; Xiaodong Liu; Idy H. T. Ho; Xiang Zhang; Jeffery Ho; Wei Hu; Yuanyuan Tian; Shanglong Kou; Chee Sam Chan; Jun Yu; Sunny H. Wong; Tony Gin; Matthew T. V. Chan; Xuegang Sun; William K. K. Wu
• Keywords: Steatohepatitis; Steatosis; Lipotoxicity; TFEB; Lipid droplet

Abstract Impaired autophagic degradation of intracellular lipids is causally linked to the development non‐alcoholic steatohepatitis (NASH). Pharmacological agents that can restore hepatic flux could therefore have therapeutic potentials for this increasingly prevalent disease. Herein, we investigated effects polydatin, a natural precursor resveratrol, in murine nutritional model NASH and cell line steatosis. Results showed oral administration polydatin protected against lipid accumulation alleviated inflammation hepatocyte damage db / mice fed methionine‐choline deficient diet. Polydatin also palmitic acid‐induced cultured hepatocytes. In both models, restored lysosomal function were impaired by or Mechanistically, inhibited mTOR signalling up‐regulated expression activity TFEB, known master regulator function. conclusion, ameliorated through restoring flux. The polydatin‐regulated autophagy was associated with inhibition pathway restoration TFEB. Our study provided affirmative preclinical evidence inform future clinical trials examining potential anti‐NASH effect humans.