The Citrus Flavonoid Naringin Confers Neuroprotection Against Cerebral Ischemia by Enhancing Endogenous Antioxidant Capacity and Suppressing Neuroinflammation

Naringin is a naturally occurring flavanone glycoside found in citrus fruits that has been widely studied for its antioxidant and anti-inflammatory activities. The precise mechanisms by which naringin exerts protective effects against ischemic stroke are not yet fully understood. To address this gap, the current study examined the efficacy of naringin administration (100 mg/kg BW) in an experimental rat model involving permanent right middle cerebral artery occlusion (Rt.MCAO). Administration of naringin significantly improved neurological performance while reducing cerebral infarct volume and brain edema following ischemic injury. Histopathological evaluation further demonstrated that naringin preserved neuronal density in the cerebral cortex and hippocampus, indicating protection against ischemia-induced neuronal degeneration. In parallel, naringin attenuated glial activation, as evidenced by reduced expression of ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), accompanied by suppression of the pro-inflammatory mediators interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). Furthermore, naringin restored redox homeostasis by lowering malondialdehyde (MDA) levels and preserving the activities of the endogenous antioxidant enzymes catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and mitochondrial superoxide dismutase (mitochondrial SOD). A significant reduction in myeloperoxidase (MPO) activity further supported its ability to alleviate oxidative stress and inflammatory responses. Our findings indicate that naringin has neuroprotective effects in experimental ischemic stroke. These effects were associated with improved antioxidant defenses and reduced neuroinflammatory responses. However, further preclinical studies are needed to confirm the underlying mechanisms, optimal treatment conditions, and long-term effects.