Neuroprotective Effect of Phytochemically Characterized Fractions of Semecarpus anacardium Against Cerebral Ischemia-Reperfusion Injury in Rats

Semecarpus anacardium Linn. (Family: Anacardiaceae), known as Bhallatak has long standing history of traditional use in neurological disorders including sciatica, epilepsy, and neuralgia, conditions corresponding to cerebrovascular insufficiency providing the ethnopharmacological rationale for this investigation. The seeds were extracted by maceration with hydroalcohol (70:30 v/v) and fractionated sequentially to yield hydroalcohol (HESA) & ethyl acetate extract (EASA). Phytochemical characterization by HPLC confirmed the presence of gallic acid (3.23% w/w) and quercetin (0.038% w/w) as marker compounds, while LC-MS identified the presence of Bhilawanol A (0.76%), Bhilawanol B (2.06%) and Anacardic acid (0.74%). EASA showed total flavonoid content of 16.55 ± 1.11 mg QE/g and total phenolic content of 12.76 ± 0.02 mg GAE/g. Neuroprotective activity was evaluated in a rat model of unilateral cerebral ischemia/reperfusion injury at doses of 87.5, 175, and 350 mg/kg. Both extracts produced dose-dependent, significant (p < 0.001) reductions in lipid peroxidation and restored antioxidant enzymes such as superoxide dismutase, catalase, and glutathione levels. Suppression of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10). EASA at dose 350 mg/kg reduced infarction area to 10.16%, comparable to sham (10.94%), with restored BBB integrity, neuronal architecture, and favourable IHC profile across HSP27, HSP72, Caspase-3 & MAP-2 markers with superior efficacy over HESA extract at all doses. Semecarpus anacardium exerts significant neuroprotection against cerebral I/R injury by attenuating oxidative stress, neuroinflammation, and apoptosis, validating its traditional ethnomedicinal use. Further mechanistic and clinical studies are warranted.