Multi-Target Intervention of Traditional Chinese Medicine in Metabolic Dysfunction–Associated Steatohepatitis: Comprehensive Treatment Strategies from Lipotoxicity to Immune Regulation

Abstract

Abstract Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction–associated steatotic liver disease (MASLD) characterized by steatosis, inflammation, hepatocellular injury, and fibrosis. The pathogenesis of MASH is complex and involves multiple factors, such as lipotoxicity, insulin resistance (IR), genetic susceptibility, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and dysregulation of the hepatic immune microenvironment. Currently, the clinical treatment for MASH remains challenging. Traditional Chinese medicine (TCM) has shown broad prospects in the prevention and treatment of MASH owing to its multi-target and multi-pathway regulation. This review summarizes the pathophysiological basis of MASH relevant to TCM intervention and discusses the effects of TCM formulas, active compounds, and comprehensive treatment strategies on lipid metabolism, IR, inflammation, autophagy and ferroptosis, intestinal barrier function, immune regulation, fibrosis, and clinical outcomes. We also discuss current clinical evidence, safety considerations, and remaining limitations, with the aim of providing a clearer basis for the clinical application and further investigation of TCM in MASH management.