Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking.
10.12122/j.issn.1673-4254.2022.01.02
- Author:
Shi ZHAO
1
;
Ke Di LIU
1
;
Jia Lin DUAN
2
;
Xing Ru TAO
1
;
Wei Hong LI
1
;
Yang BAI
3
;
Pei Feng WEI
3
;
Miao Miao XI
3
;
Hong Lian YANG
4
Author Information
1. School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
2. Institute of Medicine, Northwestern Polytechnical University, Xi'an 710072, China.
3. National Institute of Drug Clinical Trials, Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712021, China.
4. Clinical Medical Research Center, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712099, China.
- Publication Type:Journal Article
- Keywords:
molecular docking;
myocardial infarction;
network pharmacology;
pharmacodynamic substances;
traditional Chinese drugs
- MeSH:
China;
Drugs, Chinese Herbal/therapeutic use*;
Humans;
Medicine, Chinese Traditional;
Molecular Docking Simulation;
Myocardial Infarction/drug therapy*;
Network Pharmacology
- From:
Journal of Southern Medical University
2022;42(1):13-25
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.
METHODS:The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.
RESULTS:Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).
CONCLUSION:Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.
