Investigating the "homotherapy for heteropathy" mechanism of Danggui Shaoyao San in Alzheimer's disease and polycystic ovary syndrome via MAPK signaling pathway and metabolomics.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Shaoyao San (DSS), a classic TCM formula traditionally for gynecological diseases, shows promising efficacy in Alzheimer's disease (AD) per recent studies. It regulates metabolic disorders, which is a key feature of AD and polycystic ovary syndrome (PCOS), yet the mechanism of its "homotherapy for heteropathy" across these diseases remains unclear. AIM OF THE STUDY: This study aimed to verify the therapeutic effects of DSS on both AD and PCOS, and explore its underlying mechanisms involving metabolic regulation, gut microbiota modulation, and the MAPK signaling pathway. MATERIALS AND METHODS: Materials and methods: AD models were established by Aβhippocampal injection, and PCOS models by testosterone propionate combined with high-fat diet. These models were validated via behavior tests and histopathology. Network pharmacology was used to predict DSS targets. Western blot and qPCR were employed to detect the activation status of the MAPK pathway. Metabolic assays and 16 S rRNA sequencing were applied to analyze metabolic indexes and gut microbiota structure. RESULTS: DSS inhibited overactivation of the MAPK pathway in both models, which is consistent with network pharmacology predictions. It restored lipid/steroid hormone homeostasis and increased the abundance of beneficial Lactobacillus in gut microbiota, while alleviating AD and PCOS pathological phenotypes. CONCLUSION: DSS exerts "homotherapy for heteropathy" effects on AD and PCOS by synergistically regulating the MAPK pathway, metabolic balance, and gut microbiota, providing experimental evidence for its clinical application in these metabolically linked diseases.