Recent advances in traditional Chinese medicine-mediated regulation of microglial metabolic reprogramming in neurological disease therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation, driven by microglial metabolic reprogramming, underpins neurological diseases. Contrasting with the limitations of single-target therapies, TCM and acupuncture offer multi-targeted anti-inflammatory and antioxidant effects to modulate microglial activation, with TCM directly regulating microglial energy metabolism. AIM OF THE STUDY: This review aims to elucidate how TCM and acupuncture regulate microglial energy metabolism in neurological diseases, identify key metabolic enzymes and signaling pathways, and establish a scientific foundation for their translational applications. MATERIALS AND METHODS: we systematically searched major scientific databases (PubMed, Web of Science, Sinomed, and CNKI) from January 2010 to December 2025 using predefined keywords including "TCM", "acupuncture", "microglia", "glucose/lipid/amino acid metabolism", and "neurological diseases" (e.g., Alzheimer's disease, depression). Our literature review focused on two main aspects: (1) direct mechanistic studies of TCM bioactive compounds and formulas on microglial energy metabolism; (2) related studies on acupuncture's effects on brain or astrocyte metabolism, providing indirect evidence for its potential effects on glial cell metabolism. RESULTS: TCM bioactive compounds and formulas regulate metabolic enzymes and pathways, correcting microglial metabolic disturbances. These interventions promote microglial polarization toward the anti-inflammatory M2 phenotype, reducing neuroinflammation and improving outcomes in neurological diseases. Acupuncture may modulate metabolic pathways in microglia, supporting its role as an auxiliary therapeutic modality in TCM. CONCLUSION: TCM restores microglial metabolic homeostasis, enhancing M2 polarization and neuroprotection. These findings highlight TCM's potential for developing metabolism-immunity dual-target interventions for neurological diseases. Further research is needed to elucidate acupuncture's mechanisms and effects on microglial metabolism.