Use of Network Pharmacology and Molecular Docking Technology to Analyze the Mechanism of Action of Velvet Antler in the Treatment of Postmenopausal Osteoporosis.

Kuiting Guo,Enjing Luo,Tiancheng Wang,Xiangyang Leng,Baojin Yao,Mohd Ramli Elvy Suhana

doi:10.1155/2021/7144529

Abstract

Deer velvet antlers are the young horns of male deer that are not ossified and densely overgrown. Velvet antler and its preparations have been widely used in the treatment of postmenopausal osteoporosis (PMOP) in recent years, although its mechanism of action in the human body remains unclear. To screen the effective ingredients and targets of velvet antler in the treatment of PMOP using network pharmacology and to explore the potential mechanisms of velvet antler action in such treatments, we screened the active ingredients and targets of velvet antler in the BATMAN-TCM database. We also screened the relevant targets of PMOP in the GeneCards and OMIM databases and then compared the targets at the intersection of both velvet antler and PMOP. We used Cytoscape 3.7.2 software to construct a network diagram of “disease-drug-components-targets” and a protein-protein interaction (PPI) network through the STRING database and screened out the core targets; the R language was then used to analyze the shared targets between antler and PMOP for GO-enrichment analysis and KEGG pathway-annotation analysis. Furthermore, we used the professional software Maestro 11.1 to verify the predictive analysis based on network pharmacology. Hematoxylin-eosin (H&E) staining and micro-CT were used to observe the changes in trabecular bone tissue, further confirming the results of network pharmacological analysis. The potentially effective components of velvet antler principally include 17β-E2, adenosine triphosphate, and oestrone. These components act on key target genes such as AKT1, IL6, MAPK3, TP53, EGFR, SRC, and TNF and regulate the PI3K/Akt-signaling and MAPK-signaling pathways. These molecules participate in a series of processes such as cellular differentiation, apoptosis, metabolism, and inflammation and can ultimately be used to treat PMOP; they reflect the overall regulation, network regulation, and protein interactions.

Highlights

Postmenopausal osteoporosis (PMOP) refers to a metabolic disease in which the endocrine function of women’s ovaries declines after menopause and the levels of estrogen diminish, which in turn causes bone resorption by osteoclasts to exceed bone formation by osteoblasts [1,2,3]
We obtained an intersection between target points for velvet antler and postmenopausal osteoporosis (PMOP) and constructed a Venn diagram comprising a total of 233 intersection targets
The regular octagon represents the traditional Chinese medicine velvet antler, the hexagon represents PMOP, the diamond represents the effective ingredients of velvet antler, and the triangle represents the common targets of the traditional Chinese medicine velvet antler and PMOP disease

Summary

Introduction

Postmenopausal osteoporosis (PMOP) refers to a metabolic disease in which the endocrine function of women’s ovaries declines after menopause and the levels of estrogen diminish, which in turn causes bone resorption by osteoclasts to exceed bone formation by osteoblasts [1,2,3]. Research by Tseng et al showed that deer antlers prevent bone loss by promoting bone formation and reducing bone resorption [18]. Our group further demonstrated that the therapeutic effects of deer antler on treating bone diseases might be achieved through the regulation of bone formation and remodeling by controlling a series of serum proteins and signaling pathways that were essential for osteoblast and osteoclast activities [19]. Velvet antler contains various known components, the material basis and mechanism of action for use in the treatment of PMOP are still unclear

Methods

Results

Discussion

Conclusion