Objective: To investigate the intervention effect of Anemarrhenae Rhizoma (AR) on osteoporosis (OP) in rats and elucidate the potential regulatory network mechanism of AR in ameliorating OP. Methods: RNA-seq technology was employed to detect differential gene expression in the femur transcription profiles of rats. Differential metabolites in rat serum were analyzed using GC-MS. An integrated analysis of transcriptomics and metabolomics was conducted to construct the ” metabolite-gene ” interaction network. The expression of key target genes was verified through polymerase chain reaction (PCR) and western blot analysis to further clarify the regulatory mechanism of AR on OP in rats. Results: AR reversed OVX-induced femoral damage, modulated serum markers, inhibited bone resorption, promoted bone formation, and improved OP. Transcriptomics and metabolomics analysis demonstrated that AR administration altered the expression levels of 698 genes and 27 endogenous metabolites in OP rats. By constructing an interaction network of differential genes and differential metabolites, seven key metabolites and six key genes were identified. These key molecules influence amino acid metabolism, lipid metabolism, and other pathways related to bone metabolism. Conclusion: AR improved OP in rats by positively regulating changes in femoral transcriptional profiles and endogenous metabolites.
