Mechanisms of Anemarrhenae Rhizoma in Treating Osteoporosis in Rats: An Integrated Metabolomics and Transcriptomics Analysis

Objective This study aims to investigate the therapeutic efficacy of Anemarrhenae Rhizoma (AR) in a rat osteoporosis (OP) model and elucidate its underlying regulatory network mechanisms mediating OP amelioration. Methods Transcriptome profiling through RNA sequencing was utilized to identify differentially expressed genes in rat femoral tissues. Serum metabolic alterations were quantitatively assessed by gas chromatography–mass spectrometry. A combined approach incorporating both transcriptomic and metabolomic datasets enabled the establishment of molecular interaction networks between metabolites and genes. Validation of crucial molecular targets was achieved via quantitative PCR and western-blotting technique, providing mechanistic insights into AR's anti-osteoporotic activity. Results AR treatment markedly alleviated ovariectomy (OVX)-induced femoral impairment, effectively suppressing bone resorption while enhancing bone formation, ultimately ameliorating OP progression. Transcriptomic and metabolomic profiling revealed that AR intervention significantly altered the expression profiles of 698 genes and 28 endogenous metabolites in OP rats. Through constructing interaction networks of differentially expressed genes and metabolites, we identified seven pivotal metabolites and six hub genes, which were found to modulate amino acid metabolism, lipid metabolism, and other bone metabolism-related pathways, forming a multi-omics regulatory axis underlying AR's therapeutic effects. Conclusion AR exerted therapeutic effects on OP in rat models through positive regulation of femoral transcriptional profiles and endogenous metabolites.