Traditional Chinese medicine for antipsychotic-induced hyperprolactinemia: A comprehensive review of ethnopharmacological foundations, mechanistic insights, and network pharmacology perspectives.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has long employed herbal formulas for conditions manifesting as menstrual irregularities, galactorrhea, and infertility-symptom constellations overlapping with hyperprolactinemia (HPRL). Classical formulas such as Peony-Glycyrrhiza Decoction, documented for "liver constraint" patterns associated with amenorrhea, provide an ethnopharmacological rationale for investigating their relevance to antipsychotic-induced HPRL through modern mechanistic studies and network pharmacology. AIM OF THE STUDY: This review critically evaluates the scientific evidence supporting TCM interventions for antipsychotic-induced HPRL, elucidating multi-target mechanisms via network pharmacology and experimental data, thereby linking traditional uses with pharmacological validation. METHODS: This narrative review synthesizes literature from PubMed, CNKI, TCMSP, and HERB databases (January 2000-December 2024) on TCM interventions for antipsychotic-induced HPRL. Network pharmacology analyses, molecular docking studies, experimental validations, and clinical studies of individual herbs and complex formulas were critically evaluated. RESULTS: TCM ameliorates HPRL through multi-dimensional mechanisms: dopaminergic modulation via DRD2 upregulation and MAO inhibition; epigenetic regulation through DNMT inhibition and DRD2 promoter demethylation; restoration of the gut-brain-pituitary axis via microbiota modulation and anti-inflammatory effects; and regulation of key signaling pathways (JAK2/STAT5, NF-κB, PI3K/Akt). Network pharmacology reveals convergent pathway enrichment across formulas, including dopaminergic synapse, TGF-β signaling, and neuroactive ligand-receptor interactions. Clinically, Peony-Glycyrrhiza Decoction reduces prolactin by -32.69 ng/mL (p < 0.00001) with favorable safety. CONCLUSION: TCM represents a promising multi-target approach for antipsychotic-induced HPRL, addressing complex neuroendocrine dysregulation through component synergy. Network pharmacology effectively bridges TCM theory with mechanistic research, supporting evidence-based integration into psychiatric care.