Notoginsenoside R1 protects oxygen and glucose deprivation‐induced injury by upregulation of miR‐21 in cardiomyocytes

• Published in: Journal of cellular biochemistry Vol. 120; no. 6; pp. 9181 - 9192
• Main Authors: Liu, Zengjia, Wang, Haiyang, Hou, Guoliang, Cao, Honglei, Zhao, Yan, Yang, Baofa
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2019
• Subjects: 1-Phosphatidylinositol 3-kinase; acute myocardial infarction; AKT protein; Apoptosis; Cardiomyocytes; Caspase; Cell viability; Deprivation; Diabetes mellitus; Diabetic nephropathy; Glucose; Homology; Low concentrations; miRNA; miR‐21; Nephropathy; notoginsenoside R1; Oxygen; oxygen‐glucose deprivation; Panax notoginseng; phosphatase and tensin homolog; PTEN protein; Ribonucleic acid; RNA; Signal monitoring; Signal transduction; Signaling; Silence; Tensin; Up-regulation; phosphatase and tensin homolog; miR-21; oxygen-glucose deprivation; acute myocardial infarction; notoginsenoside R1
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28194

Notoginsenoside R1 (NG‐R1) is a major component of Panax notoginseng, which has been used clinically for the treatment of diabetic nephropathy for centuries in China. This study aimed to reveal the functional impacts and the underlying mechanisms of NG‐R1 on oxygen‐glucose deprivation (OGD)‐injured cardiomyocytes. Rat cardiomyocyte line H9c2 and primary cardiomyocytes were subjected to OGD with or without NG‐R1 treatment. The expression levels of miR‐21 and phosphatase and tensin homolog (PTEN) in the cell were altered by microRNA, vector or short‐hairpin RNA transfections. Thereafter, changes in cell viability, apoptosis, and PI3K/AKT signaling were monitored. NG‐R1 with low concentrations had no impact on H9c2 cells viability, but 80 μM of NG‐R1 significantly reduced cell viability. NG‐R1 (20 μM) protected H9c2 cells and primary cardiomyocytes against OGD‐induced cell damage, as cell viability was increased, apoptotic cell rate was reduced, and Bax, cleaved caspase‐3 and ‐9 were downregulated by addition of NG‐R1. MiR‐21 was low expressed in response to OGD exposure, while was highly expressed by NG‐R1 treatment. PTEN was a direct target of miR‐21. More interestingly, OGD‐induced cell damage could be recovered by miR‐21 overexpression or PTEN silence. Furthermore, PTEN silence recovered OGD‐blocked PI3K/AKT signaling pathway. To conclude, this study demonstrated that NG‐R1 exerted remarkable benefits in reduction of OGD‐induced cardiomyocyte loss. The cardioprotective actions of NG‐R1 possibly via upregulation of miR‐21, repressing the expression of miR‐21's target PTEN and thereby preventing the blockage of PI3K/AKT signaling pathway. In this study, rat cardiomyocyte line H9c2 and primary cardiomyocytes were subjected to an oxygen‐glucose deprivation (OGD) model, which is more close to mimicking the ischemic condition . Next, the functional effects of NG‐R1 on rat cardiomyocytes following OGD injury were tested. And also, the regulatory effects of NG‐R1 on miR‐21 were detected upon OGD, to reveal the underlying mechanism of which NG‐R1 exhibited cardioprotective actions.