Curcumin protects against aging-related stress and dysfunction through autophagy activation in rat brain

Curcumin (Curcuma longa) is a well-known medicinal plant that induces autophagy in various model species, helping maintain cellular homeostasis. Its role as a caloric restriction mimetic (CRM) is still being investigated. This study explores the potential of curcumin (CUR), as a CRM, to provide neuroprotection in rats with an accelerated senescence model induced by D-galactose (D-gal) via modulating autophagy. For six weeks, male rats received simultaneous supplementation of D-gal (300 mg/kg b.w., subcutaneously) and CUR (200 mg/kg b.w., oral). The oxidative stress indices, antioxidants, and electron transport chain complexes in brain tissues were measured using standard methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) gene expression analysis was used to evaluate the expression of autophagy, neuroprotection, and aging marker genes. According to our results, curcumin significantly (p≤0.05) enhanced the level of antioxidants and considerably lowered the level of oxidative stress markers. Supplementing with CUR also increased the activity of electron transport chain complexes in the mitochondria of aged brain tissue, demonstrating the antioxidant potential of CUR at the mitochondrial level. CUR was found to upregulate the expression of the aging marker gene (SIRT-1) and the genes associated with autophagy (Beclin-1 and ULK-1), as well as neuroprotection (NSE) in the brain. Our findings demonstrate that CUR suppresses oxidative damage brought on by aging by modulating autophagy. These findings imply that curcumin might be beneficial for neuroprotection in aging and age-related disorders.姜黄素（源自姜黄Curcuma longa）是一种广为人知的药用活性成分，可在多种模式物种中诱导自噬，助力维持细胞稳态。其作为热量限制模拟物（caloric restriction mimetic, CRM）的作用仍在研究之中。本研究探讨了作为热量限制模拟物的姜黄素（CUR）通过调控自噬，对D-半乳糖（D-galactose, D-gal）诱导的快速衰老模型大鼠产生神经保护作用的潜力。实验为期六周，雄性大鼠同时接受D-gal皮下注射（300 mg/kg 体重）与CUR灌胃给药（200 mg/kg 体重）。采用标准方法检测脑组织中的氧化应激指标、抗氧化物质与电子传递链复合物活性。通过逆转录聚合酶链反应（Reverse transcriptase-polymerase chain reaction, RT-PCR）基因表达分析，评估自噬、神经保护与衰老标记基因的表达水平。研究结果显示，姜黄素可显著（p≤0.05）提升抗氧化物质水平，并大幅降低氧化应激标志物水平。CUR给药还可提升衰老脑组织线粒体中电子传递链复合物的活性，证实CUR在线粒体层面的抗氧化潜能。实验发现，CUR可上调脑组织中衰老标记基因SIRT-1、自噬相关基因Beclin-1与ULK-1，以及神经保护相关基因NSE的表达。本研究结果证实，CUR可通过调控自噬抑制衰老引发的氧化损伤。上述结果表明，姜黄素或可在衰老及衰老相关疾病中发挥神经保护作用。