Plant metabolites targeting the AMPK pathway: advances in the mechanisms of action in the context of MAFLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is recognized as the hepatic manifestation of metabolic syndrome. Hepatic steatosis resulting from impaired energy metabolism constitutes the core of its pathogenesis, and this disease has become a global public health concern. AMP-activated protein kinase (AMPK) is widely expressed in high-energy-consuming organs and functions as a vital energy sensor that maintains systemic energy homeostasis. Current preclinical in vitro and in vivo evidence demonstrates that AMPK activation modulates multiple MAFLD-related pathological processes, including enhancing cellular autophagy, regulating lipid metabolism, reducing inflammatory and oxidative damage, improving IR, and mitigating mitochondrial dysfunction. Plant metabolites have attracted increasing research attention for targeting the AMPK pathway in MAFLD basic research, due to their multi-target regulatory characteristics and low adverse reaction profiles. Accordingly, based on the intrinsic connection between the AMPK signaling pathway and MAFLD, this review summarizes the research progress regarding the pharmacological mechanisms of plant metabolites acting on the AMPK pathway in MAFLD intervention. Notably, most studies included in this review are preclinical experiments conducted in vitro and in vivo, with scarce supporting clinical data. Further efforts are still needed to advance the translation of these findings and confirm their clinical potential. This review systematically summarizes recent basic research progress and identifies unresolved issues, so as to offer a theoretical basis for subsequent mechanistic studies and translational exploration of traditional Chinese medicine against MAFLD.