Abstract

Metabolic associated fatty liver disease (MAFLD) is a prevalent metabolic disorder worldwide, for which effective therapeutic options remain limited. Asiaticoside, a major bioactive compound derived from Centella asiatica, possesses anti-inflammatory and antioxidant properties; however, its role and underlying mechanisms in MAFLD remain incompletely understood. In the present study, the therapeutic effects and molecular mechanisms of asiaticoside were investigated using both in vivo and in vitro MAFLD models. MAFLD was induced in mice by a high-fat high-cholesterol diet, while palmitic acid-treated AML12 hepatocytes were used to establish an in vitro lipid metabolism disorder model. Asiaticoside treatment markedly alleviated hepatic injury, lipid accumulation, steatosis, and inflammation in vivo, and reduced lipid droplet accumulation, mitochondrial oxidative stress, and inflammatory responses in vitro. Target prediction approaches, including network pharmacology analysis, molecular docking, and cellular thermal shift assay, identified AKT as a key target, which was further validated by molecular experiments. Mechanistically, asiaticoside improved lipid metabolic homeostasis and attenuated mitochondrial dysfunction and inflammation primarily by inhibiting aberrant activation of the PI3K/AKT/mTOR signaling pathway. Collectively, these findings demonstrate that asiaticoside exerts protective effects against MAFLD and highlight its potential as a nutritional regulator for MAFLD prevention and treatment.