Narrative review examines natural herbal therapeutics targeting autophagy in metabolic-associated fatty liver disease

Metabolic-associated fatty liver disease (MAFLD) is a serious condition that can progress to cirrhosis and liver cancer. Natural herbal therapeutics, characterized by their multi-constituent and multi-target properties, as well as favorable safety profiles—particularly lower hepatorenal toxicity—are attracting significant research interest for MAFLD management. In this review, we examine their ethnopharmacological applications, with a focus on autophagy regulation. Information was gathered from traditional medical texts and online databases (e.g., PubMed and CNKI) using keywords such as “MAFLD,” “autophagy,” and “natural herbal plants.” Incorporating herbal plants into MAFLD treatment offers several advantages. First, autophagy regulation involves multiple signaling pathways (e.g., PI3K/AKT/mTOR, AMPK/TFEB, PINK1/Parkin, and Unc-51-like autophagy activating kinase 1 (ULK1)/Beclin-1/VPS34). Single-target drugs often fail to modulate this complex network effectively, whereas various medicinal plants and their bioactive compounds can simultaneously interact with key targets such as mTOR, AMPK, TFEB, SIRT1, LC3B, Beclin-1, ATG5, ULK1, and PPARγ. Second, these plants demonstrate excellent safety profiles. Traditional Chinese compound preparations, such as Zexie Decoction and Shenling Baizhu Powder, have shown clinical efficacy over centuries. To elucidate their mechanisms, researchers are now isolating bioactive compounds from these formulas for cellular and animal studies, revealing their specific roles in modulating autophagy. In summary, plant-derived bioactive compounds—especially those targeting autophagy—have shown promising clinical results against MAFLD and represent valuable candidates for future drug development.