The Active Components of Traditional Chinese Medicines Regulate the Multi-Target Signaling Pathways of Metabolic Dysfunction-Associated Fatty Liver Disease

Zhicong Song,1 Shuai Bu,2 Suzhen Sang,3 Jie Li,4 Xihai Zhang,1 Xu Song,2 Yuqin Ran1 1First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, People’s Republic of China; 2Department of Cardiology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, People’s Republic of China; 3Affiliated Hospital of Shandong Academy of Traditional Chinese Medicine, Jinan City, Shandong Province, People’s Republic of China; 4Scientific Research Office, Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, People’s Republic of ChinaCorrespondence: Shuai Bu, Department of Cardiology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 1 Jingba Road, Shizhong District, Jinan City, Shandong Province, 250001, People’s Republic of China, Email [email protected]: Metabolic dysfunction-associated fatty liver disease (MAFLD), which is characterized by hepatocyte lipid accumulation driven by systemic metabolic dysregulation, represents a critical therapeutic challenge in the context of the global metabolic syndrome epidemic. The clinically recommended drugs for MAFLD mainly include antioxidants, hepatoprotective anti-inflammatory drugs, and weight-loss drugs. However, the mechanisms underlying the progression of MAFLD is characterized by nonlinearity, highlighting the urgent need for safer multi-target alternative therapies. Although existing single-target pharmacological interventions often show limited efficacy and adverse effects, the multi-component and multi-target nature of the active ingredients in traditional Chinese medicine (TCM) formulations represent new opportunities for systemic metabolic regulation. In this study, by searching PubMed and Web of Science, we identified 108 experimental studies. By evaluating multiple mechanisms, such as improving lipid metabolism and insulin resistance, alleviating oxidative stress damage, inhibiting liver inflammation, suppressing liver fibrosis, reducing endoplasmic reticulum stress, regulating hepatocyte autophagy, inhibiting hepatocyte apoptosis, improving mitochondrial dysfunction, and regulating the intestinal flora, we constructed a cross-scale regulatory network for the treatment of MAFLD by the active components of TCM. Subsequently, the dynamic target groups were screened, and a new paradigm of “mechanism-oriented and spatiotemporal-optimized” design for TCM compound prescriptions was proposed, providing a theoretical framework for the development of precise therapies that can improve liver lipid metabolism, block inflammation and fibrosis, and restore intestinal homeostasis.Keywords: metabolic dysfunction-associated fatty liver disease, traditional Chinese medicine, active ingredient, lipid metabolism disorder, action mechanism