| Objective To analyze the pharmacological mechanism of the treatment of osteoporosis (OP) with XianlingGubao Capsule (XGC) based on network pharmacology. Methods The active components and related targets of XGC were obtained by means of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID), and Cytoscape (ver.3.7.1) was adopted for constructing the active component-target network. With OP as the key word, OP-related genes were obtained from Gene Cards: The Human Gene Database. Thereafter, Gene Ontology (GO) bioprocess enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using DAVID data analysis platform. STRING data analysis platform and Cytoscape were respectively applied for PPI network analysis and the construction of passage-target network. Results A total of 115 active components related to XGC were obtained, of which the core active components contain quercetin, kaempferol, luteolin, icariin, tanshinone IIA, etc. 280 targets are involved with the active components, whose core targets consist of PTGS2, PTGS1, ESR1, etc. The PPI network analysis demonstrated an interaction of 111 kinds of core protein, indicating a major relation with cell cycle regulation. Likewise, 46 biological processes obtained through the screening of GO enrichment are associated with cell cycle regulation as well. The process of positively regulating NF-κB transcriptional activator is one of the mechanisms of OP, which is consistent with the findings of other studies. Moreover, the KEGG pathway enrichment screened out 37 pathways in total, suggesting that the effects of XGC on OP focus on PI3K-Akt, TNF, MAPK, estrogen and other signaling pathways. Conclusion As for the core active components of XGC, flavonoids inhibit osteoclast and promote osteoblast differentiation mainly by regulating OPG/RANK/RANKL, while icaritin can improve the activity of osteoblast. In terms of the core targets, PTGS2 can restrict the expressions of M-CSF and RANKL, thus affecting the differentiations of osteoclast and osteoblast, and estrogen receptor is closely related to postmenopausal osteoporosis. Furthermore, as to the core pathways, PI3K-Akt, TNF and MAPK signaling pathways contribute to the differentiation of osteoblast. PI3K-Akt pathway also can increase bone mass. Estrogen and GnRH signaling pathways may help to provide evidences for the intervention of XGC in postmenopausal osteoporosis. Therefore, the intervention of XGC in the treatment of OP is carried out simultaneously through multiple pathways, targets and signaling pathways, which can be predicted to some extent through network pharmacology. |