期刊
PHYTOMEDICINE
卷 109, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2022.154561
关键词
NAFLD; Pterostilbene; Nrf2; Oxidative stress; Autophagy
This study provides insights into the mechanism of PTE affecting oxidative stress and autophagy in NAFLD mice.
Background: 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. Purpose: 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. Methods: Western blotting, CRISPR/Cas 9 and other molecular biological approaches were applied to explore the mechanisms of PTE effected on NAFLD. Results: 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-alpha and HO-1, and AMPK ac-tivity, 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. Conclusion: PTE effectively alleviated oxidative stress damage induced by excessive lipid accumulation in he-patocytes, thus promoting the metabolism and decomposition of fatty acids to improve NAFLD.
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