| Objective The mechanism of Xuling Jiangu Decoction in the treatment of osteoporosis (OP) was explored with integrating bioinformatics and verified with experiments. Methods Integrated bioinformatics method was adopted to analyze the compound information, the top 20 possible anti-OP key targets, mechanism and pathways. Then ovariectomy (OVX) rat models were prepared. Bone mineral density (BMD), biomechanics, micro-CT, and HE staining were performed to verify the effects in OP. Transcriptomics and the GO and KEGG analysis were performed to preliminarily validate the mechanism and the top 20 targets. qRT-PCR and Western blotting were used to further verify the expression levels of the key targets. Results One hundred and forty-four active components of the decoction could act on 242 targets which were mainly enriched in angiogenesis, stimulus response, cell proliferation, differentiation, apoptosis, migration and adhesion, bone reconstruction and osteoclastic differentiation, material metabolism. Fifty-five chemical components of 10 drugs could act on the top 20 targets and most of the components were found in Rhizoma Drynariae and Radix Dipsaci. BMD, biomechanics, and bone quality parameters in micro-CT and bone morphology could be significantly improved with the decoction. Transcriptomics showed that 679 genes were differentially expressed. The results of GO and KEGG analysis were basically consistent with those of integrated bioinformatics, which were obviously enriched in metabolic signaling pathways. The expression levels of all the top 20 targets were changed accordingly. The results of qRT-PCR and Western blotting further confirmed that the expression levels of Gapdh, Tnf, Spp1, Mmp2, Mmp1, Mapk3, Hif1a, Esr1, and other genes had opposite changes before and after modeling and treatment. Conclusion The effects of Xuling Jiangu Decoction mainly relies on Rhizoma Drynariae and Radix Dipsaci. The metabolic signaling pathway regulated by genes such as Gapdh and Hif1a may play an important role in it. |