An Lei, Li Mengxue, Zou Cunen, Wang Ke, Zhang Wei, Huang Xiaolong, Wang Yousheng
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China.
Rizhao HUAWEI Institute of Comprehensive Health Industries, Rizhao, Shandong, China.
Food Funct. 2023 Mar 20;14(6):2698-2709. doi: 10.1039/d2fo03310k.
Accumulating evidence has confirmed the health benefits of walnut diets in maintaining brain function with age. Recent studies have indicated that walnut polyphenols (WP) and their active metabolites urolithins may play an important role in the health benefits of walnut diets. In the present study, we evaluated the protective effect of WP and urolithin A (UroA) on HO-induced damage in human neuroblastoma (SH-SY5Y) cells, and investigated its mechanisms in the cAMP-response element binding protein (CREB)-mediated signaling pathway, which is tightly involved in neurodegenerative and neurological diseases. The results demonstrated that both WP (50 and 100 μg mL) and UroA (5 and 10 μM) treatment significantly reversed the decrease of cell viability, the leakage of extracellular lactate dehydrogenase (LDH), the overload of intracellular calcium and cell apoptosis induced by HO treatment. Moreover, WP and UroA treatment also relieved HO-induced oxidative stress including overproduction of intracellular reactive oxygen species (ROS) and reduced activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, western blot analysis showed that WP and UroA treatment significantly increased the activity of cAMP-dependent protein kinase A (PKA) and the expression of pCREB (Ser133) and its downstream molecule brain-derived neurotrophic factor (BDNF), which were decreased by HO treatment. Furthermore, pretreatment with the PKA inhibitor H89 abolished the protective effects of WP and UroA, indicating that up-regulation of the PKA/CREB/BDNF neurotrophic signaling pathway is required for their neuroprotective effects against oxidative stress. The current work provides new perspectives for understanding the beneficial effects of WP and UroA on brain function, which warrants further investigation.
越来越多的证据证实了食用核桃对维持老年人脑功能有益。最近的研究表明，核桃多酚（WP）及其活性代谢产物尿石素可能在食用核桃的健康益处中发挥重要作用。在本研究中，我们评估了WP和尿石素A（UroA）对人神经母细胞瘤（SH-SY5Y）细胞中HO诱导损伤的保护作用，并研究了其在环磷酸腺苷反应元件结合蛋白（CREB）介导的信号通路中的作用机制，该信号通路与神经退行性疾病和神经疾病密切相关。结果表明，WP（50和100μg/mL）和UroA（5和10μM）处理均能显著逆转HO处理诱导的细胞活力下降、细胞外乳酸脱氢酶（LDH）泄漏、细胞内钙超载和细胞凋亡。此外，WP和UroA处理还减轻了HO诱导的氧化应激，包括细胞内活性氧（ROS）的过量产生以及超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性的降低。此外，蛋白质免疫印迹分析表明，WP和UroA处理显著增加了环磷酸腺苷依赖性蛋白激酶A（PKA）的活性以及pCREB（Ser133）及其下游分子脑源性神经营养因子（BDNF）的表达，而HO处理则使其降低。此外，用PKA抑制剂H89预处理可消除WP和UroA的保护作用，表明上调PKA/CREB/BDNF神经营养信号通路是其对抗氧化应激神经保护作用所必需的。目前的工作为理解WP和UroA对脑功能的有益作用提供了新的视角，值得进一步研究。
