[Etiology, pathogenesis, and syndrome-based treatment of mitochondrial dysfunction in metabolic-associated fatty liver disease based on theory of "harmful hyperactivity and responding inhibition"].

Mitochondrial dysfunction is a key pathological mechanism in metabolic-associated fatty liver disease(MAFLD), and regulating mitochondrial function to restore normal activity is an important therapeutic strategy. The theory of "harmful hyperactivity and responding inhibition" is a classical TCM principle that explains cyclical patterns in nature, interprets physiological and pathological phenomena in the human body, and guides TCM clinical diagnosis and treatment. The mechanism of mitochondrial dysfunction closely aligns with the process described in this theory as when the responding element fails to control, the hyperactive element becomes harmful. Based on the relationship between mitochondrial function and the TCM pathogenesis of MAFLD, and applying the "harmful hyperactivity and responding inhibition" framework, this study proposes that MAFLD originates from spleen deficiency impairing nutrient transport and failing to disperse essence, kidney Yang deficiency leading to impaired Qi transformation, and insufficient mutual regulation of the two, resulting in pathological products such as excessive accumulation of phlegm-turbidity, dampness, and blood stasis. These pathological changes manifest as mitochondrial dysfunction, including mtDNA damage, hepatocyte injury, lipid peroxidation, and mitochondrial accumulation. Clinically, MAFLD treatment follows the principle of regulating the responding element and restraining the hyperactive element: reinforcing the spleen earth to restore regulation, strengthening kidney water to nourish the kidneys and harmonize the liver, and addressing phlegm-stasis obstruction and hyperactivity through blood-activating and phlegm-resolving therapies. By modulating mitochondrial structure and function, this approach improves hepatic lipid metabolism, reduces oxidative stress, and alleviates inflammatory responses, achieving multi-target therapeutic effects. This study provides new theoretical foundations and practical strategies for integrated TCM-western medicine treatment of MAFLD.