Black Currant Extract Protects against Oxidative Stress in SH-SY5Y Cells and High-Fat Diet-Induced Cognitive Impairment in C57BL/6 Mice

Black currant (<i>Ribes nigrum</i> L.) is rich in anthocyanins and other phenolic compounds with diverse health benefits. This study investigated the neuroprotective effects of black currant extract (BCE) using integrated <i>in vitro</i> and <i>in vivo</i> approaches. UHPLC-MS/MS analysis identified four major anthocyanins in BCE: delphinidin 3-<i>O</i>-glucoside, delphinidin 3-<i>O</i>-rutinoside, cyanidin 3-<i>O</i>-glucoside, and cyanidin 3-<i>O</i>-rutinoside. <i>In vitro</i>, BCE protected SH-SY5Y neuroblastoma cells against H₂O₂-induced oxidative stress in a dose-dependent manner, restoring cell viability to 77% of control levels at 50 mg/l. BCE also exhibited dose-dependent inhibition of acetylcholinesterase and butyrylcholinesterase, demonstrating cholinergic-enhancing properties. <i>In vivo</i>, C57BL/6 mice were fed a high-fat diet (HFD) for 4 weeks to induce obesity, followed by 4 weeks of oral BCE administration (50 or 200 mg/kg /day) with continued HFD feeding. Cognitive function was assessed using the Y-maze, passive avoidance, and Morris water maze tests. BCE treatment (50 mg/kg/day) significantly increased the time spent in the target quadrant compared with the HFD-only group (<i>p</i> < 0.05), suggesting that BCE mitigates HFD-induced cognitive impairment by enhancing spatial memory consolidation. BCE also showed trends toward improved performance in Y-maze and passive avoidance tests, though these did not reach statistical significance. These findings demonstrate that BCE exerts multi-target neuroprotective effects through antioxidant activity, cholinesterase inhibition, and amelioration of obesity-associated cognitive deficits, supporting its potential as a functional food ingredient for cognitive health in metabolic syndrome.