Daixie recipe ameliorates diet-induced MASH in mice via activating PI3K/AKT and Keap1/Nrf2 signaling

作者：X. He, Jiawen You, Yanyan Deng, Ying Hu, Shenglan Qi, Qian Li, Yunyi Yang, Xiaoxiao Qu, Yuxin Shao, Xinyi Fu, Shiyu Yang, Zhiying Wang, Yunhao Li, Min Zheng, Wei Liu, Hongjie Yang, Guangbo Ge, Zheng Yao, Yanming He · 发表于：Frontiers in Endocrinology · 年份：2026 · DOI：10.3389/fendo.2026.1772033 · 研究领域：Liver Disease Diagnosis and Treatment、Liver physiology and pathology、Metabolomics and Mass Spectrometry Studies

Background Metabolic dysfunction-associated steatohepatitis (MASH) is a highly prevalent liver disease that can progress to cirrhosis and hepatocellular carcinoma. Despite its growing clinical burden, effective therapies remain limited. Daixie recipe (DXR), derived from Danggui Shaoyao San in Jingui Yaolue , has shown notable clinical efficacy in treating MASH, yet its underlying pharmacological mechanisms remain to be clarified. Purpose To clarify the pharmacological effects of DXR and to elucidate the underlying mechanisms of DXR for treating MASH. Methods UHPLC-Q-Orbitrap HRMS was used to identify the phytochemcials in DXR. The key targets and ingredients for combating MASH were explored by using a suite of in vitro and in vivo experiments, as well as molecular dynamics simulations and bioinformatics analysis. The MASH model was established in C57BL/6 male mice by feeding either a high-fat, high-fructose, high-cholesterol diet or a methionine- and choline-deficient (MCD) diet. ELISA and Western Blotting were used to measure liver tissue pathology, serum biochemistry, lipid synthesis enzymes, oxidative stress markers, pro-inflammatory mediators, apoptosis-related factors, and p -AKT1, Nrf2, and HO-1 expression. The effects of DXR on the PI3K/AKT pathway and Keap1/Nrf2 signaling were analyzed in free fatty acid-induced AML12 cells and HEK293-Nrf2-Luc cells. Results DXR shows significant therapeutic efficacy in ameliorating hepatic steatosis and inflammation, as evidenced by ...