The effect and mechanism of formononetin on alleviating no-reflow after myocardial ischemia and reperfusion by up-regulating the PI3K/Akt/eNOS signal pathway activated by GPER
10.16438/j.0513-4870.2022-1442
- VernacularTitle:芒柄花黄素通过上调GPER激活PI3K/Akt/eNOS信号通路减轻心肌缺血再灌后无复流的作用及机制研究
- Author:
Hai-rui LIU
;
Lin-xi YE
;
Jia-mei-hui LIN
;
Qian LIU
;
Ya-xuan PENG
;
Ting CHEN
- Publication Type:Research Article
- Keywords:
cardioprotective effect;
molecular mechanism;
network pharmacology;
formononetin;
G protein-coupled estrogen receptor;
PI3K/Akt/eNOS
- From:
Acta Pharmaceutica Sinica
2023;58(6):1496-1504
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the cardioprotective effect of formononetin (FMN) on no-reflow (NR) after myocardial ischemia-reperfusion and its molecular mechanism based on integrated pharmacology and experimental verification, firstly, human breast cancer MCF-7 cells and myocardial NR rats were used to confirm the estrogenic activity and the effect of alleviating NR of FMN, respectively. Male SD rats were divided into Sham, NR, FMN (20 mg·kg-1) and sodium nitroprusside (SNP, 5.0 mg·kg-1) groups, which were administered once a day for one week, the experiment was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (TCM-LAEC2019095). The pharmacological analysis and in vivo study of NR rats were integrated to reveal the mechanism of FMN improving NR. The results showed that FMN had estrogenic effect and reduced NR by improving cardiac structure and function, reducing NR, ischemic myocardial area and pathological injury of cardiomyocytes. Integrated pharmacology predicts that the mechanism of FMN improving NR is mainly related to phosphatidyinositol-3-kinase-protein kinase B (PI3K-Akt) signal pathway. Phytoestrogens play a role in cardiovascular protection mainly by activating G protein-coupled estrogen receptor (GPER). GPER is also an important regulator in the upstream of PI3K-Akt signaling pathway. This study found that FMN can significantly activate GPER, p-PI3K, p-Akt and phospho-endothelial nitric oxide synthase (p-eNOS). It has good binding ability with GPER and eNOS protein. In this study, through the integration of pharmacology and experimental evaluation, it is revealed that FMN activates PI3K/Akt/eNOS signal pathway by activating GPER, thus significantly improving NR.
