Ginsenoside Rk1 Ameliorates Non-Alcoholic Fatty Liver Disease by Targeting CD36 to Modulate the AMPK Signaling Pathway.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder associated with obesity and insulin resistance. Ginsenoside Rk1 (Rk1), a natural compound extracted from ginseng, exerts various pharmacological effects, including anti-inflammatory, hepatoprotective, hypolipidemic, and insulin-sensitizing properties. This study investigated the therapeutic effects of Rk1 on NAFLD induced by a Western diet in mice and explored the underlying molecular mechanisms. The results showed that Rk1 treatment significantly reduced weight gain, improved insulin sensitivity, and attenuated liver damage and lipid accumulation in the mice. RNA sequencing and molecular analyses showed that Rk1 downregulated the expression of the fatty acid translocase CD36, and restored AMP-activated protein kinase phosphorylation. Furthermore, Rk1 alleviated hepatic inflammation and oxidative stress in NAFLD mice by affecting the sirtuin 1 (SIRT1) and forkhead box O1 (FOXO1) pathways and regulated fatty acid synthesis by affecting the expression of the mechanistic target of rapamycin complex 1 (mTORc1) and sterol regulatory element-binding protein 1c (SREBP1). These findings highlight the potential of Rk1 as a natural therapeutic agent for NAFLD and contribute to research on the use of functional foods and bioactive compounds for metabolic disease management.