Multi-omics reveals total flavones from Abelmoschus manihot (L.) Medik. [Malvaceae] ameliorate MAFLD via PI3K/AKT/mTOR-mediated autophagy

作者：Chao Lv, Lei Zhao, Jiani Hou, Hongyin Sun, Ziyuan Li, Yuesong Wu, Peizheng Shi, Yaping Xiao, Yunjin Xie, Wei Su, Mingzhu Yin · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1601707 · 被引用次数：6 · 研究领域：Liver Disease Diagnosis and Treatment、Bioactive Compounds in Plants、Diabetes, Cardiovascular Risks, and Lipoproteins

Introduction: Metabolic-associated fatty liver disease (MAFLD) has emerged as a global health crisis, which is characterized by hepatic lipid accumulation, inflammation, and fibrosis. Currently, effective therapeutic strategies for MAFLD are still scarce. Methods: This study aimed to explore the hepatoprotective effects and underlying mechanisms of total flavones from Abelmoschus manihot (L.) Medik. (Malvaceae), abbreviated as TFA, in the context of MAFLD. Ultra-high-performance liquid chromatography-quadrupole orbitrap mass spectrometry (UHPLC-QTOF-MS) was used to identify the metabolites in TFA. MAFLD mice induced by a high-fat diet were treated with TFA at doses of 50 and 100 mg/kg. Body weight gain, hepatic lipid accumulation, and serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TC), and triglycerides (TG) were determined. Histological analysis was performed to evaluate hepatic steatosis, fibrosis, as well as the levels of inflammatory cytokines (IL-6, TNF-α) and antioxidant markers (SOD, GSH). Transcriptomic and metabolomic analyses were carried out to explore the molecular mechanisms. In vitro studies were conducted in HepG2 cells, and the role of autophagy was investigated using the autophagy inhibitor 3-MA. Results: Using UHPLC-QTOF-MS, 56 metabolites were identified in TFA, including hyperoside, rutin, and quercetin derivatives, which possess anti-lipidemic and anti-inflammatory properties. In MAFLD mice, TFA treatment sign...