Shengyang Sanhuo decoction and its disassembled prescriptions improve chronic fatigue syndrome in mice: Insights from lipid metabolism and autophagy

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic fatigue syndrome (CFS) is a chronic intractable disease, displaying abnormal energy metabolism, resulting in significant energy deficiency. Shengyang Sanhuo Decoction (SYSH), with its exquisite compatibility of traditional Chinese medicine (TCM), has been clinically used for treating CFS. However, its pharmacological mechanisms remain underexplored. AIM OF THE STUDY: To analyse the therapeutic effects of SYSH and its disassembled prescriptions (Group A: Qi-tonifying; Group B: Wind-dispelling) on CFS, with a focus on autophagy function and lipid metabolism. METHODS: A multi-stress-induced CFS mouse model was established. Behavioural assessments, transmission electron microscopy, serum biochemistry, and Western blot were performed to evaluate the regulation of autophagy and energy homeostasis. Chemical composition was analysed using LC-MS/MS, and mechanisms elucidated through integrated network pharmacology and lipidomics. RESULTS: SYSH, Group A, and Group B significantly ameliorated fatigue-like behaviours and reduced serum biomarkers, including lactate dehydrogenase (LDH), creatine kinase (CK), and blood urea nitrogen (BUN). Treatments elevated adenosine triphosphate (ATP) levels and modulated the autophagy signalling pathway to promote autophagosome-lysosome formation. Crucially, Group A predominantly restored phospholipid (PC/PE), while Group B primarily modulated the sphingolipid (ceramide/S1P) rheostat. CONCLUSIONS: SYSH and its disassembled prescriptions alleviated CFS by regulating lipid metabolism: Qi-tonifying herbs preferentially enhance phospholipid availability, while wind-dispelling herbs more prominently restore sphingolipid homeostasis, supporting the TCM formula compatibility theory.