[Research progress on traditional Chinese medicine for metabolic-associated fatty liver disease via regulating MAPK...

Metabolic-associated fatty liver disease(MAFLD) is one of the most prevalent chronic liver diseases worldwide. Its complex pathogenesis involves multiple pathological processes, including insulin resistance, lipid metabolism disorder, inflammation, oxidative stress, and apoptosis. The mitogen-activated protein kinase(MAPK) signaling pathway serves as a critical hub linking these sections. It plays a central role in MAFLD occurrence and progress, identified as a key therapeutic target. Recent studies have shown that active compounds, single herbs, and traditional Chinese medicine(TCM) formulas can improve the MAFLD pathological state via regulating the MAPK pathway. This review systematically summarized the primary mechanisms of the MAPK signaling pathway in MAFLD. Additionally, this review highlighted the research progress on TCM active components, including flavonoids, terpenoids, quinones, and phenolic acids, as well as herbs and formulas such as Bupleuri Radix, Artemisiae Scopariae Herba, Polygoni Multiflori Radix Praeparata, Yinchenhao Decoction, and Erhuang Quzhi Formula in intervening in insulin resistance, lipid metabolism, inflammation, oxidative stress, autophagy, and apoptosis via regulating c-Jun N-terminal kinase(JNK), p38 MAPK, extracellular signal-regulated kinase 1/2(ERK1/2), and other classical pathways. It was found that TCM improved metabolic disorder and liver function in a coordinated manner via multi-target and multi-pathway regulation of the MAPK signaling network, demonstrating unique advantages in integrative regulation. Future studies illustrate the multi-target regulation mechanisms of TCM by exploring the direct binding mechanisms between TCM active components and MAPK key kinases. Specifically, future research should be concentrated on TCM in the specific regulation of MAPK subtypes, and the interaction between MAPK and metabolic pathways such as the peroxisome proliferator-activated receptor(PPAR) signaling, while further clinical trials should be conducted, aiming to provide theoretical and experimental support for MAFLD prevention and treatment, as well as TCM new medicine research and development.