Deciphering the Underlying Mechanism of Eucommiae Cortex against Osteoporotic Fracture by Network Pharmacology

BACKGROUND: Du Zhong (DZ), or Eucommiae Cortex, a traditional Chinese herbal medicine, has been used to treat osteoporosis. Although it has been reported that DZ can improve bone mass in ovariectomized rats, its pharmacological mechanisms in treating osteoporotic fractures (OPF) remain unclear. METHODS: In this study, we used a network pharmacological manner to explore its potential complicated mechanism in treating OPF. We obtained DZ compounds from TCMSP and BATMAN-TCM databases and collected potential targets of these compounds through target fishing based on TCMSP and BATMAN-TCM databases. Next, we collected the OPF targets by using CTD, GeneCards, OMIM, HPO, and GenCLiP 3 databases. And then the overlapping genes between DZ potential targets and OPF targets were used to build up the protein-protein interaction (PPI) network and to analyze their interactions and find out the big hub genes in this network. Subsequently, clusterProfiler package in R language was utilized to conduct the enrichment of Gene Ontology biological process and KEGG pathways. RESULTS: There were totally 93 active compounds and 916 related targets in DZ. After the enrichment analysis, we collected top 25 cellular biological processes and top 25 pathways based on the adjusted P value and found that the DZ anti-OPF effect was mainly associated with the regulation of ROS and inflammatory response. Furthermore, 64 hub genes in PPI network, such as MAPK1 (degree = 41), SRC (degree = 39), PIK3R1 (degree = 36), VEGFA (degree = 31), TP53 (degree = 29), EGFR (degree = 29), JUN (degree = 29), AGT (degree = 29), MAPK1, SRC, PIK3R1, VEGFA, and TP53, were considered as potential therapeutic targets, implying the underlying mechanisms of DZ acting on OPF. CONCLUSION: We investigated the possible therapeutic mechanisms of DZ from a systemic perspective. These key targets and pathways provided promising directions for the future research to reveal the exact regulating mechanisms of DZ in treating OPF.