Aqueous extract of Artemisia capillaris Thunb. herbal tea alleviates liver injury in MASLD mice and lipotoxicity in HepG2 cells by inhibiting apoptosis and promoting autophagy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic metabolic disorder characterized by diffuse hepatic steatosis. Excessive lipid accumulation induced by a high-fat diet can trigger hepatocyte apoptosis and impair autophagic flux, thereby aggravating liver injury. Artemisia capillaris Thunb. herbal tea contains multiple bioactive constituents with hepatoprotective, choleretic, and lipid-regulatory activities. Therefore, this study aimed to evaluate the protective effects of Artemisia capillaris Thunb. herbal tea aqueous extract (ACTE) against MASLD-associated hepatic lipid accumulation and liver injury and to investigate whether ACTE alleviates high-fat diet (HFD)-induced liver injury by modulating AKT-associated apoptotic signaling and mTOR-regulated autophagic flux. We employed an HFD-induced MASLD mouse model and a palmitic acid/oleic acid (PO)-induced lipotoxic HepG2 cell model. Hepatic injury and lipid accumulation were assessed by histological analysis and serum biochemical parameters. The involvement of AKT and mTOR signaling pathways was further verified using the AKT activator SC79 and the mTOR inhibitor rapamycin. The experimental results showed that ACTE significantly reduced hepatic lipid accumulation and improved lipid metabolic homeostasis in MASLD mice. ACTE also enhanced hepatic AKT phosphorylation, restored the Bcl-2/Bax balance, and suppressed caspase-dependent apoptosis; meanwhile, it decreased mTOR phosphorylation and P62 accumulation and enhanced hepatic autophagy. In PO-treated HepG2 cells, ACTE similarly reduced lipid accumulation and apoptosis, restored mitochondrial membrane potential and autophagic flux, and ameliorated abnormalities in AKT/Bcl-2/caspase-mediated apoptotic signaling and mTOR-related autophagic signaling. Further experiments with SC79 and rapamycin supported the involvement of these pathways. In conclusion, ACTE alleviated liver injury in MASLD mice and lipotoxic injury in HepG2 cells by activating AKT-associated anti-apoptotic signaling and restoring mTOR-regulated autophagy.