Neuroprotective Effect of Combined Pomegranate and Candesartan Therapy Against Chronic Cerebral Ischemia in Rats

Abstract Background Stroke remains a leading cause of mortality worldwide. Ischemic stroke, caused by arterial occlusion, induces sensorimotor deficits and memory impairments. Excessive activity of the brain angiotensin II type 1 receptor (AT1R) is associated with hypertension and cerebral ischemia. Candesartan (CN), an AT1R blocker, improves cerebrovascular blood flow. Pomegranate ( Punica granatum ) is rich in polyphenolic antioxidants that reduce oxidative stress and inflammation, suggesting potential neuroprotective effects in cerebral ischemia. Aim This study compared the neuroprotective effects of CN administered alone or in combination with pomegranate (POM) in a rat model of cerebral ischemia induced by chronic unilateral carotid artery ligation. Methods Cerebral ischemia was induced by ligation of the right common carotid artery (RCCA) in adult rats. Animals were randomly assigned to four groups: sham control, untreated ischemic, ischemic treated with CN, and ischemic treated with CN + POM. Sensorimotor and cognitive functions were assessed 1–15 days post-surgery using beam balance (BB), beam walking (BW), modified sticky-tape (MST), novel object recognition (NOR), and the Morris water maze (MWM) tests. Results RCCA ligation induced marked sensorimotor deficits and memory impairments. Both CN monotherapy and CN + POM treatment equally restored sensorimotor function to sham-control levels, as demonstrated by BB, BW, and MST tests. In contrast, CN + POM treatment showed greater efficacy than CN alone in improving short-term recognition and spatial memory, as demonstrated by NOR and MWM performance. Conclusion CN effectively reverses ischemia-induced sensorimotor deficits, whereas the addition of POM confers specific and enhanced protection against cognitive impairment, indicating distinct mechanisms underlying sensorimotor and memory recovery after cerebral ischemia.