Hesperidin provides synergistic effect in conferring neuroprotection to rats maintained on a regimen of alternate day fasting

Background. Alternate day fasting (ADF) is a beneficial dietary intervention that reduces age- associated complications. Hesperidin is a potential antioxidant especially known for free radical scavenging ability. Oxidative damages are a major cause of neurological changes in brain that accelerates deteriorative effects leading to aging. In the current study, we aimed to investigate the role of hesperidin supplementation on neuroprotection conferred in terms of redox balance in rats that were maintained on an ADF regimen. Methods and Results. Middle aged male Wistar rats (Rattus Norvegicus) (12-15 months) were divided into four groups: Group I. Control; Group II. ADF; Group III. Hesperidin; Group IV. ADF+ Hes (maintained under ADF regimen and given hesperidin regularly). The number of rats maintained in each group is 6. We measured crucial biomarkers of antioxidant defense like FRAP, GSH, SOD, catalase, and oxidative stress MDA, PCO, AOPP, NO, inflammatory cytokine (IL-6 and TNF-α) and autophagy expression. The results provide evidence of a synergistic benefit obtained in crucial parameters of antioxidant defense including FRAP, GSH, SOD, catalase and autophagy expression (Beclin gene) alongwith decrease in MDA, PCO, AOPP, NO and inflammation markers. The activity of the mitochondrial electron transport chain complexes showed increased efficiency and the histopathological changes show well protected neurons and lesser neurodegeneration. Conclusion. The results support administration of hesperidin during ADF regimen to obtain additional benefits and protection from aging induced oxidative stress and to reduce the incidence of common metabolic morbidities like impaired glucose levels and attenuate redox imbalance thus conferring neuroprotective effects.

研究背景：交替日禁食（Alternate Day Fasting, ADF）是一种可有效减轻衰老相关并发症的膳食干预手段。橙皮苷（hesperidin）是一种具有潜在抗氧化活性的物质，其自由基清除能力尤为突出。氧化损伤是引发脑部神经退行性改变的主要诱因，会加速衰老相关的恶化进程。本研究旨在探讨橙皮苷补充对维持交替日禁食方案的大鼠氧化还原平衡相关神经保护作用的影响。

研究方法与结果：选取12~15月龄的中年雄性Wistar大鼠（褐家鼠*Rattus Norvegicus*），随机分为4组：对照组（I组）、交替日禁食组（II组）、橙皮苷组（III组）、交替日禁食+橙皮苷组（IV组，维持交替日禁食方案并定期给予橙皮苷），每组各6只大鼠。检测抗氧化防御系统的关键生物标志物，包括铁还原抗氧化能力（FRAP）、谷胱甘肽（Glutathione, GSH）、超氧化物歧化酶（Superoxide Dismutase, SOD）、过氧化氢酶，以及氧化应激指标丙二醛（Malondialdehyde, MDA）、蛋白质羰基（Protein Carbonyl, PCO）、晚期氧化蛋白产物（Advanced Oxidation Protein Products, AOPP）、一氧化氮（Nitric Oxide, NO）、炎症因子（白细胞介素6（Interleukin-6, IL-6）与肿瘤坏死因子α（Tumor Necrosis Factor-α, TNF-α））和自噬表达水平。结果显示，抗氧化防御关键参数（包括FRAP、GSH、SOD、过氧化氢酶及自噬相关基因Beclin的表达）均呈现协同提升趋势，同时MDA、PCO、AOPP、NO及炎症标志物水平显著降低。线粒体电子传递链复合物活性有所增强，组织病理学检查结果显示神经元保护良好，神经退行性变程度减轻。

研究结论：本研究结果支持在交替日禁食方案中联合使用橙皮苷，可获得额外益处，能够抵御衰老诱导的氧化应激，降低血糖受损等常见代谢疾病的发生率，缓解氧化还原失衡，从而发挥神经保护作用。