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Astragaloside IV Protects Rat Cardiomyocytes From Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a

Astragaloside IV Protects Rat Cardiomyocytes From Hypoxia-Induced Injury by Down-Regulation of miR-23a and miR-92a

Licheng Gong, Hong Chang, Jingze Zhang, Gongliang Guo, Jingwei Shi, Haiming Xu

Cell Physiol Biochem. 2018;49(6):2240-2253.

PMID: 30257251

Abstract:

Background/aims:
Astragaloside IV (AS-IV), a traditional Chinese medicine isolated from Astragalus membranaceus, has been shown to exert cardioprotective effect previously. This study aimed to reveal the effects of AS-IV on hypoxia-injured cardiomyocyte.
Methods:
H9c2 cells were treated with various doses of AS-IV for 24 h upon hypoxia. CCK-8 assay, flow cytometry/Western blot, and qRT-PCR were respectively conducted to measure the changes in cell viability, apoptosis, and the expression of miR-23a and miR-92a. Sprague-Dawley rats were received coronary ligation, and were administrated by various doses of AS-IV for 14 days. The infarct volume and outcome of rats followed by ligation were tested by ultrasound, arteriopuncture and nitrotetrazolium blue chloride (NBT) staining.
Results:
We found that 10 μg/ml of AS-IV exerted myocardioprotective effects against hypoxia-induced cell damage, as AS-IV significantly increased H9c2 cells viability and decreased apoptosis. Interestingly, the myocardioprotective effects of AS-IV were alleviated by miR-23a and/or miR-92a overexpression. Knockdown of miR-23a and miR-92a activated PI3K/AKT and MAPK/ ERK signaling pathways. Bcl-2 was a target gene for miR-23a, and BCL2L2 was a target gene for miR-92a. In the animal model of myocardial infarction (MI), AS-IV significantly reduced the infarct volume, ejection fraction (EF), shortening fraction (FS) and LV systolic pressure (LVSP), and significantly increased left ventricular end-diastolic internal diameter (LVEDd). And also, the elevated expression of miR-23a and miR-92a in MI rat was reduced by AS-IV.
Conclusion:
AS-IV protected cardiomyocytes against hypoxia-induced injury possibly via down-regulation of miR-23a and miR-92a, and via activation of PI3K/AKT and MAPK/ERK signaling pathways.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP127615605	3-Nitrotetrazolium blue chloride		127615-60-5	Price

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