Exploring the Mechanism of Action of Guhuaisi Kangfu Pill for Treating Steroid-induced Osteonecrosis of the Femoral Head Based on WGCNA and Animal Experiment Validation
10.19378/j.issn.1003-9783.2024.09.004
- VernacularTitle:基于WGCNA和动物实验探究骨坏死康复丸治疗激素性股骨头坏死的作用机制
- Author:
Wenxi LI
1
,
2
,
3
;
Liangyu TIAN
;
Jin ZHANG
;
Caihong SHEN
;
Zhimin YANG
;
Jiaqiao GUO
;
Yuju CAO
Author Information
1. 郑州中医骨伤病医院,河南 郑州 450016
2. 河南省骨坏死研究中医药重点实验室,河南 郑州 450016
3. 河南省骨伤病中医诊疗工程技术研究中心,河南 郑州 450016
- Keywords:
steroid-induced osteonecrosis of the femoral head;
Guhuaisi Kangfu Pill;
network pharmacology;
weighted gene co-expression network analysis(WGCNA);
validation experiment;
rats
- From:
Traditional Chinese Drug Research & Clinical Pharmacology
2024;35(9):1306-1318
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the main pharmacological basis and mechanism of action of Guhuaisi Kangfu Pill(GHSKF)in the treatment of steroid-induced osteonecrosis of the femoral head(SONFH).Methods The active constituents and targets of GHSKF were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases.The speculative targets of SONFH were screened out based on GeneCards and Online Mendelian Inheritance in Man(OMIM)databases.The gene modules and hub genes of SONFH were identified using a weighted gene co-expression network analysis(WGCNA).The intersection of the two targets and the result of WGCNA was taken to obtain the potential targets of GHSKF for the treatment of SONFH.The key active constituents were screened with the"active constituent-target"network,which was constructed by the Cytoscape software.Then,the STRING database was used to construct the protein interaction network to screen the key targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of key targets was performed,and the relationship between key active constituent,key targets and key signaling pathways was explored.Finally,the molecular docking between key active constituents and key targets was verified.In addition,the SONFH rat model was used for experimental verification.Results A total of 146 compounds and the corresponding 346 targets were identified based on the TCMSP database.A total of 4 187 targets of SONFH were obtained based on GeneCards and OMIM databases.In addition,twelve gene modules and 2 556 hub genes of SONFH were screened out based on WGCNA.Quercetin,luteolin and kaempferol were key active ingredients for the treatment of SONFH.Various signaling pathways such as PI3K/AKT were involved.Molecular docking showed the key active ingredients had good binding activity with the key targets.The results of animal experiments demonstrated that GHSKF could improve bone biological alterations by up-regulating AKT1,PI3K,RUNX2,and down-regulating the expression of Caspase-3 and IL-6(P＜0.01),which verified some results of the network pharmacology prediction.Conclusion We analyzed the potential mechanism of action of GHSKF for the treatment of SONFH using network pharmacology and animal experiments,which may provide a reference for further research on its pharmacological basis and targets.
