Kolaviron offered a novel cardioprotection against ischemic/reperfusion injury by modulation of Akt/protein kinase B (PKB)/p38MAPK/Caspase 3/poly‐ADP‐ribose polymerase signaling pathway

Abstract

Free radical generation and oxidative stress have been implicated in the pathogenesis and pathophysiology of ischemic/reperfusion injury. Kolaviron is a bioflavonoid with arrays of biological and pharmacological activities. The study was designed to investigate the modulatory role of Kolaviron on ischemic/reperfusion injury in experimental animal models. Twenty male Wistar albino rats were randomly divided into two groups of ten rats per group: Group 1 received corn oil as a vehicle (Control) and rats in Group 2 were pre‐treated with Kolaviron at 200 mg/kg for 4 weeks. After 4 weeks of Kolaviron administration, hearts were excised and mounted on the working heart perfusion system. Western blot analysis for protein expressions was carried out on frozen heart samples. Results revealed significant (p < 0.05) reduction in the activity of cardiac catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)with concomitant reduction in oxygen radical absorbance capacity (ORAC) in ischemic rat heart of Control compared to group pre‐treated with Kolaviron. Similarly, intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) contents were significantly elevated in control compared to Kolaviron pre‐treated rats. Western blot showed that pre‐treatment with Kolaviron significantly increased total Akt/protein kinase B (PKB), phosphorylated Akt/PKB at serine 473 with concomitant significant reduction in the expressions of p38 mitogen‐activated protein kinase (p38MAPK), Caspase 3, and cleaved poly adenosine diphosphate ribose polymerase (PARP). Taken together, Kolaviron offered significant cardioprotection via free radical scavenging activity and upregulation of pro‐survival signaling pathway.