Diosgenin attenuates nonalcoholic hepatic steatosis through the hepatic SIRT1/PGC-1α pathway.

Autor: Meng D; The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Yin G; The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Chen S; The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Zhang X; The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Yu W; The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Wang L; Traditional Chinese Medicine College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Liu H; Traditional Chinese Medicine College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Jiang W; The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Sun Y; Traditional Chinese Medicine College of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China., Zhang F; Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People's Republic of China. Electronic address: fxzhang0987@163.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Aug 15; Vol. 977, pp. 176737. Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1016/j.ejphar.2024.176737
Abstrakt: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide in recent years, causing severe economic and social burdens. Therefore, the lack of currently approved drugs for anti-NAFLD has gradually gained attention. SIRT1, as a member of the sirtuins family, is now the most widely studied in the pathophysiology of many metabolic diseases, and has great potential for preventing and treating NAFLD. Natural products such as Diosgenin (DG) have the potential to be developed as clinical drugs for the treatment of NAFLD due to their excellent multi-target therapeutic effects. In this study, we found that DG can activate the SIRT1/PGC-1α pathway and upregulate the expression of its downstream targets nuclear respiratory factor 1 (NRF1), complex IV (COX IV), mitofusin-2 (MFN2), and PPARα (perox-isome proliferator-activated receptor α) in SD rats induced by high-fat diet (HFD) and HepG2 cells caused by free fatty acids (FFAs, sodium oleate: sodium palmitate = 2:1). Conversely, the levels of dynamin-related protein 1 (DRP1) and inflammatory factors, including NF-κB p65, IL6, and TNFα, were downregulated both in vitro and in vivo. This improved mitochondrial dysfunction, fatty acid oxidation (FAO), lipid accumulation, steatosis, oxidative stress, and hepatocyte inflammation. Subsequently, we applied SIRT1 inhibitor EX527 and SIRT1 agonist SRT1720 to confirm further the necessity of activating SIRT1 for DG to exert therapeutic effects on NAFLD. In summary, these results further demonstrate the potential therapeutic role of DG as a SIRT1 natural agonist for NAFLD. (Graphical Abstracts).
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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