Apigenin Alleviates Myocardial Reperfusion Injury in Rats by Downregulating miR-15b

Abstract

Background We investigated whether apigenin could mitigate myocardial reperfusion injury in rats, and a possible mechanism was proposed. Material/Methods The I-R injury model was established in rats along with a sham group as control, and the expressions of microRNA-15b (miR-15b), JAK2, and p-JAK2 in the myocardia of the 2 groups were detected. Apoptosis and reactive oxygen species (ROS) were also detected. Rats in the I-R injury model were divided into 3 groups in vivo : the 1I-R group, the 2I-R+solvent group, and the 3I-R+apigenin group. Expression of miR-15b, JAK2, p-JAK2, STAT3, and p-STAT3 in the myocardia of the 3 groups were detected. ROS content, apoptosis, MDA content, SOD, and CAT activities were detected. Rat myocardial H9C2 cells were cultured in vitro and divided into 5 treatment groups in vitro; expressions of miR-15b, JAK2, p-JAK2, STAT3, and p-STAT3 in H9C2 cells were detected, and the apoptosis and ROS content were detected by flow cytometry. Results We found that the increased miR-15b expression during myocardial I-R injury in rats downregulated the expression of JAK2 and activity of the JAK2-STAT3 pathway, promoted myocardial apoptosis and ROS production, and aggravated myocardial I-R injury. Apigenin treatment can downregulate miR-15b expression, increase the expression of JAK2 and the activity of JAK2-STAT3 pathway, reduce myocardial apoptosis and ROS production, and alleviate myocardial I-R injury. Conclusions Api treatment downregulated the expression of miR-15b and upregulated the expression of JAK2 and the activity of the JAK2-STAT3 pathway, thereby alleviating myocardial I-R injury, cardiomyocyte apoptosis, and ROS production in vitro .

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

“…Thus, an in vivo study by Wang et al shows that the increased cardiac miR-15b expression observed during myocardial I/R injury in rats correlates with the decreased expression of JAK2 and activity of JAK2/STAT3 pathway, with augmented myocardial apoptosis and ROS production, and aggravated heart injury [206]. Apigenin treatment of I/R rats downregulates miR-15b expression in the heart, improves the altered mechanisms and alleviates myocardial I/R injury [206]. In an in vivo report, Bian et al showed that luteolin pretreatment induces anti-apoptotic effects by decreasing miR-208b-3p expression in myocardial tissue of I/R rats [207].…”

“…Recent studies evidenced that apigenin and luteolin modulate the expression of certain epigenetic factors, in particular miRNAs, that constitute fine regulators of the oxidative and inflammatory stress. Thus, an in vivo study by Wang et al shows that the increased cardiac miR-15b expression observed during myocardial I/R injury in rats correlates with the decreased expression of JAK2 and activity of JAK2/STAT3 pathway, with augmented myocardial apoptosis and ROS production, and aggravated heart injury [206]. Apigenin treatment of I/R rats downregulates miR-15b expression in the heart, improves the altered mechanisms and alleviates myocardial I/R injury [206].…”

Polyphenols in the Mediterranean Diet: From Dietary Sources to microRNA Modulation

“…This miR was found to be increased during myocardial RI, determining a downregulation of JAK2 that promotes myocardial apoptosis and ROS production, aggravating the myocardial injury. Apigenin treatment can downregulate miR-15b expression and increase the expression of Janus kinase 2 (JAK2) and the activity of Signal transducer and activator of transcription 3 (STAT3) pathway, reducing myocardial apoptosis and ROS production and alleviating myocardial RI [ 48 ]. Lastly, in mice, apigenin improved glucose intolerance by suppression of matured miR103 expression levels [ 49 ].…”

Regulation of miRNAs by Natural Antioxidants in Cardiovascular Diseases: Focus on SIRT1 and eNOS

“…Flavanones and flavones are mainly found in high concentrations in the same citrus fruits, such as oranges and lemons [ 17 ]. Apigenin, a major plant flavone present in chamomile, can alleviate MI after AMI [ 168 ]. Apigenin plays a role in conferring protection against myocardial injury by reducing the expression of miR-15b [ 168 ].…”

“…Apigenin, a major plant flavone present in chamomile, can alleviate MI after AMI [ 168 ]. Apigenin plays a role in conferring protection against myocardial injury by reducing the expression of miR-15b [ 168 ]. Apigenin also attenuates TGF-β1-stimulated cardiac fibroblast differentiation, and its mechanisms are associated with the reduction in miR-155-5p expression [ 162 ].…”