6-Gingerol protects cardiomyocytes against hypoxia-induced injury by regulating the KCNQ1OT1/miR-340-5p/ PI3K/AKT pathway

Background: Hypoxia could induce cardiomyocytes injury and lead to heart disease. Studies have shown that 6-Gingerol has a protective effect on cardiomyocytes injury, but its molecular mechanism is still unclear.

Methods: Cell counting kit 8 (CCK8) and flow cytometry assays were used to measure the viability and apoptosis of cardiomyocytes. Western blot (WB) analysis was performed to assess the levels of proliferation, apoptosis, and phosphatidylinositol 3- kinase/protein kinase B (PI3K/AKT) signaling pathway-related proteins. The reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were detected by their corresponding Assay Kits. Besides, the expression levels of potassium voltage-gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1) and microRNA-340-5p (miR-340-5p) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the interaction between KCNQ1OT1 and miR-340-5p.

Results: Hypoxia could inhibit the viability and enhance the apoptosis and oxidative stress of cardiomyocytes to induce cardiomyocytes injury, while 6-Gingerol could alleviate this effect. Overexpression of KCNQ1OT1 aggravated hypoxia-induced cardiomyocytes injury and reversed the protective effect of 6-Gingerol on cardiomyocytes injury. Besides, miR-340-5p could be sponged by KCNQ1OT1, and its overexpression could invert the promotion effect of KCNQ1OT1 overexpression on hypoxia-induced cardiomyocytes injury. Moreover, miR-340-5p expression was regulated by 6-Gingerol and KCNQ1OT1. In addition, hypoxia inactivated the PI3K/AKT signaling pathway, whereas 6-Gingerol and miR-340-5p could reverse this effect.

Conclusions: 6-Gingerol could hinder the expression of KCNQ1OT1 to protect cardiomyocytes from hypoxia-induced injury through regulation of the miR-340-5p/ PI3K/AKT pathway, providing a new mechanism of 6-Gingerol protecting cardiomyocytes from injury.