Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway

Abstract

Aim:The dried tuber root of Ophiopogon japonicus has been used in the traditional Chinese medicine for treatment of myocardial ischemia and thrombosis. In this study we investigated the effects of methylophiopogonanone A (MO-A), a major homoisoflavonoid in Ophiopogon japonicus, on myocardial ischemia/reperfusion (I/R) injury. Methods: Mice were pretreated with MO-A (10 mg· kg -1 ·d -1 , po) for 2 weeks and then subjected to transient occlusion of the left anterior descending coronary artery. Cardiac function was evaluated, and the infarct size and apoptosis index were assessed. The mechanisms underlying the cardio-protection of MO-A were analyzed in H9C2 rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The cell viability and apoptosis were evaluated; apoptotic and relevant signaling proteins were analyzed. NO levels in the culture medium were assessed. Results: In I/R mice, pretreatment with MO-A significantly reduced the infarct size (by 60.7%) and myocardial apoptosis (by 56.8%), and improved cardiac function. In H9C2 cells subjected to H/R, pretreatment with MO-A (10 μmol/L) significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production. Furthermore, pretreatment with MO-A markedly increased the activation of PI3K/Akt/eNOS pathway in H9C2 cells subjected to H/R, and the protective effects of MO-A were abolished in the presence of the PI3K inhibitor wortmannin (100 nmol/L). Conclusion: MO-A attenuates I/R-induced myocardial apoptosis in mice via activating the PI3K/Akt/eNOS signaling pathway.

MicroRNA-449a Inhibition Protects H9C2 Cells Against Hypoxia/Reoxygenation-Induced Injury by Targeting the Notch-1 Signaling Pathway

“…The cell viability was assessed using the methylthiotetrazole (MTT) assay kit (Beyotime, China) according to the manufacturer’s protocol and previously reported protocol [17]. …”

“…Then, 20 µg of total protein was separated by 10% sodium dodecyl sulfate–polyacrylamide gel electrophoresis and transferred to nitrocellulose membranes (Millipore, MA, USA). The membranes were blocked for 30 min at 37°C with 5% nonfat dry milk and subsequently incubated with primary antibodies overnight at 4°C according to a previous protocol [17]. The primary antibodies against Notch-1, Notch-1 intracellular domain (Notch-1 ICD), Hes-1, cleaved caspase-3, caspase-3, and β-actin were purchased from Cell Signaling Technology (Shanghai, China).…”

Hydromorphine postconditioning protects isolated rat heart against ischemia‐reperfusion injury via activating P13K/Akt/eNOS signaling

“…PI3K/Akt is a transmembrane signal transduction cascade involved in the growth and apoptosis of myocardial cells, which also regulate coronary angiogenesis and downstream signal transduction . He et al demonstrated that activating the PI3K/Akt/eNOS signaling pathway attenuates myocardial apoptosis induced by ischemic‐reperfusion (I/R) in mice via cleaving caspase‐3 expression, elevating the Bcl‐2/Bax ratio, and restoring NO production.…”

Exercise Preconditioning Plays a Protective Role in Exhaustive Rats by Activating the PI3K‐Akt Signaling Pathway

“…It is involved in the regulation of important physiological functions such as cell activation, protein synthesis, and mediates numerous external stimulus signals to induce cell growth, differentiation, survival, apoptosis, and malignancy. Akt activates directly on multiple targets such as the apoptotic family of Bcl, nuclear transcription factor-κB (NF-κB) and nitric oxide synthase (NOS) and inhibits apoptosis by reducing open mPTP [30]. But, the mechanism of myocardial apoptosis is complex and involves multiple targets; whether EP reduces the myocardial apoptosis in exhausted Figure 6: e effect of EP on the levels of p-PI3K, p-Akt, Bad, Bax, Bcl-2, and caspase-3 proteins in the rat myocardium after EE (x ± s, n � 6).…”