Pterostilbene alleviated NAFLD via AMPK/mTOR signaling pathways and autophagy by promoting Nrf2

• DOI: 10.1016/j.phymed.2022.154561
• Publication Date: 2022-11-21T07:15:06Z
• Authors: Bingyu Shen; Yeling Wang; Jiaqi Cheng; Yi Peng; Qiaoling Zhang; Zheng Li; Lilei Zhao; Xuming Deng; Haihua Feng
• Keywords: Pterostilbene

NAFLD is a liver disease that is caused by liver damage or extreme lipid deposition but not alcohol. Nrf2 could mediate resistance to oxidative stress injury. Autophagy can degrade metabolic waste and accumulated toxic endogenous substances. Pterostilbene (PTE) is an active compound extracted from blueberry, and grape, that exhibits many biological effects, such as antiinflammation and antitumor.This study provides a mechanism of PTE affecting on oxidative stress and autophagy in NAFLD mice. Tyloxapol, oil acid (OA) and palmitic acid (PA) were used to induce lipid accumulation in mice and HepG2 cells.Western blotting, CRISPR/Cas 9 and other molecular biological approaches were applied to explore the mechanisms of PTE effected on NAFLD.PTE pretreatment effectively reduced the lipid accumulation in OA and PA induced HepG2 cells and tyloxapol induced mice, and significantly promoted the expression of nNrf2, PPAR-α and HO-1, and AMPK activity, but inhibited the expression of mTORC 1 and SREBP-1c. PTE activated phosphatidylinositide 3-kinase (PI3K) and proteins in the autophagy-related gene (ATG) family, and promoted the transformation of LC3Ⅰ to LC3Ⅱ which indicated the activation of autophagy, however, these effects were abolished after Nrf2 knockout.PTE effectively alleviated oxidative stress damage induced by excessive lipid accumulation in hepatocytes, thus promoting the metabolism and decomposition of fatty acids to improve NAFLD.