| Objective To explore the mechanism of Liuwei Dihuang pills in the treatment of postmenopausal osteoporosis based on clinical trials combined with network pharmacology. Methods (1) Sixty postmenopausal osteoporosis patients with kidney-yin deficiency syndrome were randomly divided into treatment group and control group. The patients in two groups received vitamin D and calcium. In addition, patients in the treatment group received Liuwei Dihuang pills and patients in the control group received oral raloxifene. After 6 months of treatment, bone mineral density of the lumbar spine (L1-4) and the right femoral neck and the levels of serum osteocalcin (OCN) and serum anti-tartrate acid phosphatase-5b (TRAP-5b) were determined. (2) According to the TCMSP database, the active ingredients of Liuwei Dihuang pills and their corresponding targets were screened. The targets related to postmenopausal osteoporosis were obtained from the three databases, GeneCards, OMIM, and Drugbank. The interaction between active ingredient targets and postmenopausal osteoporosis was the treatment target of Liuwei Dihuang pill for postmenopausal osteoporosis. Cytoscape 3.7.2 software was used to construct the interaction network between active ingredients, targets, and proteins. STRING database was used for PPI network analysis. Metascape data analysis platform was used for GO biological process enrichment and KEGG pathway enrichment analysis. Results Compared with those before the treatment, bone mineral density increased, OCN value reflecting the bone formation index significantly increased, and TRAP-5b value of the bone resorption index significantly reduced in both groups. Those in the treatment group had a more obvious effect than in the control group (P<0.05). According to network pharmacology predictions, there were 36 active ingredients of Liuwei Dihuang pills acting on postmenopausal osteoporosis. The top three active ingredients were quercetin, kaempferol, and catechin. The main targets were interferen regulatory factor-1 (IRF1), oncostatin M (OSM), and interleukin 6 (IL-6). GO enrichment analysis showed that biological processes were mainly involved in cytokine-mediated signaling pathways and apoptosis signaling pathways, cell composition mainly included protein kinase complexes and plasma membrane protein complexes, and molecular functions mainly included transcription factor binding and nuclear receptor activity. KEGG enrichment analysis obtained the relevant signal pathways including JAk-STAT, Wnt, and NF-κB signal pathways. Conclusion Liuwei Dihuang pills significantly increases bone mineral density, promotes bone formation, and inhibits bone resorption. Its mechanism of action for postmenopausal osteoporosis is based on the application of active ingredients such as quercetin, kaempferol, targeting catechins, and IRF1, OSM, and IL-6, and acting through JAk-STAT, Wnt, and NF-κB signaling pathways. |