Rhapontigenin Improves Non-alcoholic Fatty Liver Disease by Inducing Lipophagy Through
the ACOX1, mTOR/ULK1 Pathways Ying-Xiao Wang1, Xin-Ge Ke1, Chen Wang1, Kang-Bo Peng1, He-Zhen Wu1,2,3★, Yan-Fang Yang1,2,3★ Corresponding author
- 1Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, CHINA.
- 2Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan, CHINA.
- 3Modern Engineering Research Center of Traditional Chinese Medicine and Ethnic Medicine of Hubei Province, Wuhan, CHINA.
CORRESPONDENCE
He-Zhen Wu
Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, CHINA.
Volume 20, Issue 1 · pp. 43–56 · PUBLISHED 2024 · DOI: 10.1177/09731296231197299
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ABSTRACT
Background: Non-alcoholic fatty liver disease (NAFLD) is severely affecting the quality of people’s life. Rhapontigenin (RA) is a stilbene compound isolated from Rhubarb L., which has been reported to have an effect on cholesterol diet-induced hyperlipidemia in rats. This study aims to explore the pharmacodynamics and the mechanism of RA obtained from Rheum franzenbachii Munt. against NAFLD. RA was extracted from the roots of the Rheum L. (Polygonaceae) plant Rheum franzenbachii Munt. Materials and Methods: RA was extracted by Sephadex-gel column and identified by high-performance liquid chromatography (HPLC)-UV and HR-ESI-MS. The pharmacodynamic indexes of L-02 cells and mice treated with RA were determined by histological staining and ELISA, while the expression of autophagy-related proteins was analyzed by Western blot. Results: The results in vivo showed that the liver structure of RA-treatment mice was normal, and the organ coefficient was significantly decreased. It also showed that RA could significantly reduce the expression of reactive oxygen species (ROS) in the liver as well as inhibit oxidative stress and inflammatory response. Interestingly, the autophagy inhibitor 3-methyladenine (3-MA) could reverse the effect of RA on NAFLD, which further confirmed that RA plays an anti-NAFLD role through activating lipophagy. Conclusion: It suggested that RA has an effect on NAFLD by down-regulating the expression of Acyl-CoA oxidase 1 (ACOX1), p-mTOR, and p-Unc-51-like kinase 1 (ULK1), then inhibiting Acetyl-CoA (A-CoA) production, and up-regulating the expression of autophagy protein 5 (Atg5) to promote the lipophagy of lipocytes.
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ACOX, T., Wang, M. P. Y., Ke, X., Wang, C., Peng, K., Wu, H., & Yang, Y. (2024). Rhapontigenin Improves Non-alcoholic Fatty Liver Disease by Inducing Lipophagy Through. Pharmacognosy Magazine, 20(1), 43–56. https://doi.org/10.1177/09731296231197299