Mechanism of Orcinol Glucoside in Treatment of Osteoporosis： An Exploration Based on Network Pharmacology and in Vitro Validation
10.13422/j.cnki.syfjx.20211519
- VernacularTitle:基于网络药理学和体外实验研究苔黑酚葡萄糖苷治疗骨质疏松的分子机制
- Author:
Xia LIU
1
;
Ming-chun HUANG
2
;
Xiao-qiong ZHANG
1
;
Jie LI
2
;
Mei ZHANG
1
Author Information
1. State Key Laboratory of Southwestern Chinese Medicine Resources，School of Pharmacy， Chengdu University of Traditional Chinese Medicine（TCM），Chengdu 611137，China
2. Chongqing Hospital of TCM，Chongqing 400021，China
- Publication Type:Journal Article
- Keywords:
orcinol glucoside （OG）;
osteoporosis;
network pharmacology;
molecular docking;
in vitro validation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(1):197-203
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo predict the therapeutic targets and related signaling pathways of orcinol glucoside （OG） in the treatment of osteoporosis by network pharmacology， and further clarify its mechanisms based on molecular docking and in vitro cell model. MethodThe pharmacological targets of OG were obtained from Similarity ensemble approach （SEA） and SwissTargetPrediction， and the targets related to osteoporosis from DisGeNET and GeneCards. The cross-analysis was conducted to screen the common targets between OG and osteoporosis. STRING was used to construct the protein-protein interaction （PPI） network， followed by topology analysis using CytoNCA plug-in of Cytoscape 3.7.2 to screen out the core targets. The obtained common targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） analysis by g：Profiler. AutoDock Vina was utilized for molecular docking， and the in vitro cell experiments were then carried out for verifying the mechanism of OG in treating osteoporosis. ResultA total of 73 targets related to OG and osteoporosis were harvested，among which 14 were proved to be key targets by topological analysis. GO and KEGG functional enrichment analysis yielded 259 cell biological processes， mainly involving organonitrogen compound metabolic process， cell population proliferation， protein metabolic process， regulation of response to stress， and response to chemicals. Its mechanism of action might be related to advanced glycation end-product （AGE）-AGE receptor （RAGE） signaling pathway， interleukin-17 （IL-17） signaling pathway， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. Molecular docking indicated that the binding energies of OG to Cyclin D1 （CCND1） and cyclin-dependent kinase 4 （CDK4） were the lowest and similar. The results of flow cytometry showed that compared with the normal group， OG group exhibited decreased proportion of cells in G0/G1 phase （P<0.01） and decreased proportion of cells in S phase （P<0.01）. As demonstrated by Western blot， compared with the normal group， OG up-regulated the protein expression levels of Cyclin D1 and CDK4 （P<0.05， P<0.01）. ConclusionOG alleviates osteoporosis via multiple targets and multiple pathways. It may exert the therapeutic effects by increasing Cyclin D1 and CDK4 protein expression to change cell cycle and promote cell proliferation.
