Network Pharmacology and Molecular Docking Elucidate the Pharmacological Mechanism of the OSTEOWONDER Capsule for Treating Osteoporosis

Jiashuang Fan; Jianli Zhou; Zhuan Qu; Hangya Peng; Shuhui Meng; Yaping Peng; Tengyan Liu; Qiu Luo; Lifen Dai

doi:10.3389/fgene.2022.833027

Network Pharmacology and Molecular Docking Elucidate the Pharmacological Mechanism of the OSTEOWONDER Capsule for Treating Osteoporosis

Front Genet. 2022 Feb 28:13:833027. doi: 10.3389/fgene.2022.833027. eCollection 2022.

Authors

Jiashuang Fan¹, Jianli Zhou², Zhuan Qu², Hangya Peng², Shuhui Meng², Yaping Peng³, Tengyan Liu³, Qiu Luo⁴, Lifen Dai^{1

2}

Affiliations

¹ Department of Internal Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
² Department of Internal Medicine, Yunnan Fuwai Cardiovascular Hospital, Kunming, China.
³ Medical School, Kunming Medical University, Kunming, China.
⁴ Department of Internal Medicine, The Affiliated Hospital of Yunnan University, Kunming, China.

Abstract

Background: Osteoporosis (OP) is a serious and common bone metabolic disease with bone mass loss and bone microarchitectural deterioration. The OSTEOWONDER capsule is clinically used to treat OP. However, the potential regulatory mechanism of the OSTEOWONDER capsule in treatment of OP remains largely unknown. Methods: The bioactive compounds of herbs and their targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The speculative targets of OP were screened out based on GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. The gene modules and hub genes of OP were identified using a weighted gene co-expression network analysis (WGCNA). Then, an herb-compound-target network was constructed based on the above analyses. The biological function of targets was subsequently investigated, and a protein-protein interaction (PPI) network was constructed to identify hub targets of OP. Finally, molecular docking was performed to explore the interaction between compounds and targets. Results: A total of 148 compounds of eight herbs and the corresponding 273 targets were identified based on the TCMSP database. A total of 4,929 targets of OP were obtained based on GeneCards, DisGeNET, and OMIM databases. In addition, six gene modules and 4,235 hub genes of OP were screened out based on WGCNA. Generally, an herb-compound-target network, including eight herbs, 84 compounds, and 58 targets, was constructed to investigate the therapeutic mechanism of the OSTEOWONDER capsule for OP. The biofunction analysis indicated 58 targets mainly associated with the bone metabolism, stimulation response, and immune response. EGFR, HIF1A, MAPK8, IL6, and PPARG were identified as the hub therapeutic targets in OP. Moreover, the interaction between EGFR, HIF1A, MAPK8, IL6, PPARG, and the corresponding compounds (quercetin and nobiletin) was analyzed using molecular docking. Conclusion: Our finding discovered the possible therapeutic mechanisms of the OSTEOWONDER capsule and supplied the potential therapeutic targets for OP.

Keywords: OSTEOWONDER capsule; WGCNA; molecular docking; network pharmacology; osteoporosis.