Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia.
10.1007/s11655-023-3644-x
- Author:
Po-Li LIN
1
;
Jun-Ling CAO
1
;
Ping REN
1
;
Jia-Li CHEN
2
;
Bo-Ya CAO
1
;
Ping HE
3
;
Chang-Hui ZHENG
1
;
Qi-Wen LI
1
;
Wei WANG
4
;
Jian ZHANG
5
Author Information
1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
2. School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
3. School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China.
4. School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
5. School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China. zhangjian@bucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
acute myocardial infarction;
energy metabolism;
hormone;
inflammation;
tetrahydropalmatine
- MeSH:
Humans;
Matrix Metalloproteinase 9;
Network Pharmacology;
Cyclooxygenase 2;
Molecular Docking Simulation;
PPAR gamma;
Myocardial Ischemia/genetics*;
Glucose;
RNA;
Drugs, Chinese Herbal/therapeutic use*;
Serotonin Plasma Membrane Transport Proteins
- From:
Chinese journal of integrative medicine
2023;29(12):1087-1098
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI).
METHODS:First, the target genes of THP and AMI were collected from SymMap Database, Traditional Chinese Medicine Database and Analysis Platform, and Swiss Target Prediction, respectively. Then, the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally, the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR in vivo and in vitro.
RESULTS:MMP9, PPARG, PTGS2, SLC6A4, ESR1, JAK2, GSK3B, NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function, as well as alleviated myocardial cell damage. Furthermore, THP significantly decreased the RNA expression levels of MMP9, PTGS2, SLC6A4, GSK3B and ESR1 (P<0.05, P<0.01) after AMI. In vitro, THP significantly increased H9C2 cardiomyocyte viability (P<0.05, P<0.01) and inhibited the RNA expression levels of PPARG, ESR1 and AR (P<0.05, P<0.01) in OGD model.
CONCLUSIONS:THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation, the improvement of energy metabolism and the regulation of hormones.
