Koenimbine Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Down-Regulating PERK/ATF-4 and Apaf-1/IRE1α Signaling Pathways

Background: Ischemic stroke is a significant contributor to enduring impairment and mortality worldwide, resulting from the abrupt obstruction of cerebral blood flow and the ensuing pathophysiological processes that ultimately induce neuronal damage and apoptosis. This research study primarily aims to ascertain the neuroprotective effects of koenimbine in a rat model of ischemic stroke. Method: The rats underwent the middle cerebral artery occlusion (MCAO) procedure to induce cerebral ischemia/reperfusion damage. The rats were administered oral koenimbine at dosages of 25 and 50 mg/kg two hours after the MCAO surgery. The infarction extent, neurological impairment score, and cerebral water content of the experimental rats were assessed. Inflammatory cytokines, biomarkers, oxidative stress markers, acetylcholine esterase (AChE), and proteins from the PERK/ATF-4 and Apaf-1/IRE1α pathways were assessed using commercial kits. Results: The current findings demonstrated that koenimbine treatment mitigated neurological deficits, reduced brain water content, and decreased infarction levels in rats subjected to cerebral ischemic-reperfusion injury. The koenimbine therapy reduced pro-inflammatory cytokine levels and alleviated oxidative stress by enhancing antioxidant levels. The koenimbine therapy down-regulated the PERK/ATF-4 and Apaf-1/IRE1α pathways in rats subjected to cerebral ischemia-reperfusion damage. Conclusions: This study revealed the neuroprotective effects of koenimbine in rats subjected to cerebral ischemia-reperfusion injury. These findings may promote the development of koenimbine as a potential therapeutic drug to prevent or alleviate brain injury caused by ischemic stroke.