Network Pharmacology-Based Strategy and Molecular Docking to Explore the Potential Mechanism of Jintiange Capsule for Treating Osteoporosis.

Background: With the advent of ageing population, osteoporosis (OP) has already become a global challenge. Jintiange capsule is extensively applied to treat OP in China. Although recent studies demonstrate that it generates significant effects on strengthening bone, the exact mechanism of the jintiange capsule for treating OP remains unknown.

Purpose: To understand the main ingredients of the jintiange capsule, predict the possible targets and the relevant signal transduction pathways, and explore the mechanism of the jintiange capsule for the treatment of OP.

Methods: Main ingredients of the jintiange capsule, drug targets, and potential disease targets for OP were obtained from public databases. Molecular biological processes and signaling pathways were determined via bioinformatic analysis, containing protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the disease-drug-ingredient-targets-pathways networks were constructed using Cytoscape. According to CytoNCA, core targets were acquired. Finally, the present study conducted molecular docking for better testing the abovementioned results.

Results: In the current work, we found that 4 main ingredients of the jintiange capsule, 33 drug targets, 4745 potential disease targets for OP, and 12 overlapping targets were identified. PPI network containing 12 nodes and 25 edges proved that there existed a complex relationship. As revealed by GO functional annotation, the intersected targets were mostly associated with BP, CC, and MF. The targets were enriched to 368 items in BP, 27 items in CC, and 42 items in MF. They mainly included calcium ion homeostasis, calcium channel complex, and calcium channel regulator activity. According to KEGG pathway analysis, the intersected targets were mostly associated with Rap 1, cGMP-PKG, Ras, cAMP, calcium pathways, and so on. Based on the analysis with CytoNCA, we acquired 4 core targets, respectively-CALR, SPARC, CALM1, and CALM2. Besides, 2 core targets, CALR and CALM1, were selected for molecular docking experiments. Molecular docking revealed that the main ingredient, calcium phosphate, had good binding with the CALR protein and CALM1 protein.

Conclusion: To conclude, the main ingredient of the jintiange capsule, particularly calcium phosphate, may interact with 2 targets, CALR and CALM1, and regulate multiple signaling pathways to treat OP. Additionally, this also benefits us in further understanding the mechanism of the jintiange capsule for treating OP.