Ononin inhibits cerebral ischemia/reperfusion injury via suppression of inflammatory responses in experimental rats and SH-SY5Y cells

The cerebral ischemic stroke is a major type of stroke characterized by brain injury, neurological deficits, and cognitive impairments, which accounts for increased disability and mortality worldwide. The present study focusses to investigate the therapeutic efficacy of ononin against the ischemic stroke induced by ischemia–reperfusion (I/R) injury via suppression of I/R injury stimulated neuroinflammation in rat model. Animals were separated into four groups as Sham, I/R induced, I/R + ononin pretreated (10 mg/kg body weight), and I/R + ononin pretreated (20 mg/kg body weight). The ischemic stroke was stimulated in animals by middle artery occlusion method as described previously. The infarct volume, brain edema, and neurological deficits were studied by standard methods. The oxidative stress markers like SOD, CAT, GSH, GSH-Px, Cu/Zn-SOD, Mn-SOD, MDA, and acetylcholinesterase were assessed by previously described methods. The contents of TNF-α, IL-1β, and IL-6 were assessed using assay kits. The in vitro studies were performed using SH-SY5Y neuroblastoma cells. The level of Ononin given at 10 and 20 mg/kg body weight resulted in increase in water content, reduced volume of infarct, improved neurological deficit score, and exerted its antioxidant, anti-inflammatory and neuroprotective efficacy against cerebral I/R injury-induced rats. Increase in proinflammatory cytokine expression was observed in cerebral I/R injury-stimulated rats. Oxygen glucose deprivation/ reoxygenation (OGD/R) injury showed reduction in cell viability of SH-SY5Y cells which was attenuated following treatment with ononin at varying concentrations. Ononin has reduced proinflammatory cytokine expression in vitro. Thus, ononin has successfully attenuated I/R injury-induced neuroinflammation in rats and thus minimized neuronal injury. Therefore, all the findings of the study depicts that ononin can thus be used as a beneficiary move toward treatment of cerebral I/R injury.