Jiangu granules ameliorate postmenopausal osteoporosis via rectifying bone homeostasis imbalance: A network pharmacology analysis based on multi-omics validation

Postmenopausal osteoporosis (PMOP) is a series of reactions to bone homeostasis dysregulation mediated by estrogen deficiency in elderly women. Jiangu granules, a traditional Chinese medicine formula, has been proven as an effective treatment approach for PMOP, which still needs more research iin its complex regulatory mechanisms. Our study aimed to identify the putative targets and regulatory mechanisms of Jiangu granules in PMOP treating. We utilized the NHANES database to compare the clinical information of normal population and PMOP patients. Associated with transcriptomics and proteomic data, we identified the PMOP-related genes, and further studied them with bioinformatic methods including and prognosis model. Network pharmacology was applied for confirming the action targets of Jiangu granules in PMOP. We verified the safety and effectiveness in PMOP treatments of Jiangu granules, and also demonstrated our hypothesis in rats. We discovered that the PMOP patients had higher monocytes than the normal women. Moreover, the transcriptomics and proteomic analysis suggested that the dysregulation of PMOP-related genes expression was associated with monocytes, and the Notch pathway were the critical targets representing bone homeostasis imbalance highly involved in the occurrence of PMOP. We also ascertained network pharmacology results further revealing that Jiangu granules might treat PMOP via recovering the bone homeostasis imbalance identified above. In vivo experiments, we confirmed the high efficacy which mainly resulted from function in mitigating the imbalance in bone homeostasis by recovering the normal expression of PMOP-related genes associated with monocytes, Notch, and steroid pathway in the rat models. Our finding underscored the clinical potential of Jiangu granules in treating PMOP, and enriched the comprehension of the related pathogenic and therapeutic mechanisms.