In Vivo Neuroprotective Effects of Alpinetin Against Experimental Ischemic Stroke Damage Through Antioxidant and Anti-Inflammatory Mechanisms

Ischemic stroke is the most common type of stroke and poses a major global health challenge due to its high mortality and lasting disability impact. The onset and progression of ischemic stroke are largely linked to oxidative stress and inflammatory responses. Alpinetin, a natural flavonoid found in the ginger family, exhibits various pharmacological properties, including antioxidant and anti-inflammatory activities. In this study, the neuroprotective potential of alpinetin in attenuating oxidative stress and inflammation against cerebral ischemic stroke was evaluated. Ninety male Wistar rats were randomly assigned to the sham operation group, the Rt.MCAO group, the Rt.MCAO+piracetam group, and the Rt.MCAO+alpinetin groups (25, 50, and 100 mg/kg BW). Cerebral infarction size, neuronal density, and antioxidant and anti-inflammatory activities were measured. Three days of treatment with alpinetin markedly reduced the infarct volume by 30% compared to the Rt.MCAO+vehicle-treated group. Additionally, rats treated with alpinetin exhibited a significant increase in neuronal density in the cortex, as well as in the CA1 and CA3 regions of the hippocampus. Furthermore, treatment with alpinetin ameliorated both the Rt.MCAO-induced increase in malondialdehyde (MDA) activity and the Rt.MCAO-induced decrease in catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in the cortex and hippocampus. Moreover, COX-2 and IL-6 protein levels were assessed using western blotting. The results showed that treatment with alpinetin (100 mg/kg BW) significantly reduced the expression levels of COX-2 and IL-6 in both the cortex and hippocampus. Our findings suggest that alpinetin significantly mitigates the effects of cerebral ischemia-induced brain damage through its antioxidant and anti-inflammatory properties and could potentially be developed as a therapeutic agent for stroke treatment.