Vine tea (Ampelopsis grossedentata) ameliorates chronic alcohol-induced hepatic steatosis, oxidative stress, and inflammation via YTHDF2/PGC-1α/SIRT3 axis

Abstract

For over a millennium, the leaves of Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang, commonly known as vine tea, have been revered as a popular tea and traditional herbal remedy, possessing antioxidant, anti-inflammatory, hepatoprotective, and antiviral properties. In recent years, the incidence of alcohol-related liver injury has been on the rise, imposing a significant public health burden worldwide. Previous studies have indicated that extracts of vine tea (AGE) can ameliorate alcoholic liver disease (ALD), yet the pharmacological mechanisms underlying this effect remain poorly understood. In this study, we first employed UPLC-Q-TOF-MS to analyze the chemical constituents of AGE. Subsequently, an ALD model was established in mice fed with Lieber-DeCarli diet, and the hepatoprotective benefits of AGE were assessed by measuring biochemical indicators and hepatic pathological changes. Moreover, a suite of bioinformatics tools, including transcriptomics, weighted gene co-expression network analysis, and single-cell data mining, were utilized to reveal that the YTHDF2/PGC-1α/SIRT3 signaling axis may be the potential mechanism by which AGE exerts its anti-ALD effects. Additionally, Western blotting and immunofluorescence staining techniques were employed to further substantiate the aforementioned mechanism. Our findings demonstrate that administration of vine tea significantly alleviated chronic ethanol-induced hepatic lipid accumulation, oxidative stress, and inflammation. Notably, knockdown of YTHDF2 partially protected the liver from ethanol-induced injury. Mechanistically, bioinformatics analysis and in vitro and in vivo experiments identified YTHDF2 as a key pharmacological target of AGE in treating ALD, acting through the downstream PGC-1α/SIRT3 pathway. In summary, in this study, we provide the first evidence that AGE mitigates ethanol-induced liver injury by inhibiting YTHDF2 and enhancing the expression of PGC-1α and SIRT3. Vine tea, as a tea food with unique medicinal value, shows significant potential and value in the treatment of ALD.