Study of Isopsoralen on the Postmenopausal Osteoporosis Based on the Network Pharmacology and Bioinformatics

Abstract

Background: Isopsoralen, which comes from the fruit of the traditional Chinese medicine Psoralea corylifolia, has been identified as a kind of phytoestrogen and has been proved to be effective for the treatment of osteoporosis. However, the mechanism underlying ispsoralen’s anti-osteoporotic effects remains unknown. The purpose of this study was to study the effects and mechanisms of isopsoralen’s anti-osteoporosis activity by bioinformatics in combination with in vitro and in vivo experiments. Materials and methods: The targets and biological mechanisms of isopsoralen’s anti-osteoporotic effects were predicted by bioinformatics. Then an ovariectomized (OVX) mice model and a H2O2-induced bone marrow mesenchyml stem cell (BMSCs) model were used to detect the effects of isopsoralen on postmenopausal osteoporosis and to verify the predicted targets. Results: The results predicted that IPRN could protect against osteoporosis through several targets including EGFR, AKT1, SRC, CCND1, ESR1 (ER-α), AR, PGR, BRCA1, PTGS2, and IGF1R. In vivo and in vitro studies confirmed that isopsoralen could inhibit the bone loss induced by OVX in mice and promote the osteogenic differentiation of BMSCs damaged by H2O2 by inhibiting oxidative stress and apoptosis. Moreover, isopsoralen could significantly produce the above effects through upregulating estrogen receptors. These findings suggested that isopsoralen might be a therapeutic agent for postmenopausal osteoporosis prevention by acting as an estrogen replacement agent and a natural antioxidant. Conclusion: This study provided a comprehensive functional analysis of isopsoralen on the treatment of osteoporosis and provided a potential drug for the treatment of postmenopausal osteoporosis. Funding Information: This work was supported in part by grants from the National Natural Science Foundation of China [82073851] and Important Science Fund of Science and Technology Bureau of Liaoning Province [2020JH2/10300056]. Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: All animal studies complied the Guidelines for the Care and Use of Laboratory Animals of the National Institutes of Health and all experimental protocols in the current study were approved by the institutional animal care committee of Dalian Medical University (Dalian, China; Certificate of Conformity: No. SCXK 2018-0007).