Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China.
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China.
J Nutr Biochem. 2018 Jun;56:16-25. doi: 10.1016/j.jnutbio.2018.01.009. Epub 2018 Feb 2.
Neuroinflammation is documented to be the major culprit of Alzheimer's disease. Lycopene (LYC), a fat soluble carotenoid, exhibits neuroprotective function in several neurodegenerative disorders. However, the effects of LYC to countering systemic inflammation-induced amyloidogenesis and memory deficiency remain to be elucidated. In current study, 3-month-old male C57BL/6J mice were treated with 0.03% LYC (w/w, mixed into normal chow) for 5 weeks. The mice were then treated by intraperitoneal injection of LPS (0.25mg/kg) for 9 days. It was found that LYC inhibited LPS-induced memory loss by behavior tests including Y-maze test and Morris water test. Meanwhile, LYC prevented LPS-induced accumulation of Aβ, levels of amyloid precursor protein (APP), and suppressed neuronal β-secretase BACE1 and elevated the expressions of α-secretase ADAM10. Furthermore, LYC down-regulated the expression of IBA-1 (a marker of microglia activation), reduced the levels of inflammatory mediators and inhibited oxidative stress in LPS-treated mice. Moreover, LYC suppressed the phosphorylation of MAPKs, NFκB, and activated Nrf2 signaling pathways in LPS-treated BV2 microglial cells. Therefore, our study indicated that LYC could ameliorate LPS-induced neuroinflammation, oxidative stress, amyloidogenesis and cognitive impairments possibly through mediating MAPKs, NFκB and Nrf2 signaling pathways, indicating that LYC might be a nutritional preventive strategy in neuroinflammation-related diseases such as AD.
神经炎症被认为是阿尔茨海默病的主要罪魁祸首。番茄红素（LYC）是一种脂溶性类胡萝卜素，在几种神经退行性疾病中表现出神经保护功能。然而，LYC 对抗系统性炎症诱导的淀粉样蛋白形成和记忆缺陷的影响仍有待阐明。在本研究中，3 月龄雄性 C57BL/6J 小鼠用 0.03% LYC（w/w，混入正常饲料）处理 5 周。然后，用 LPS（0.25mg/kg）腹腔注射处理小鼠 9 天。结果发现，LYC 通过 Y 迷宫测试和 Morris 水迷宫测试等行为测试抑制 LPS 诱导的记忆丧失。同时，LYC 防止 LPS 诱导的 Aβ 积累、淀粉样前体蛋白（APP）水平升高，并抑制神经元 β-分泌酶 BACE1，同时升高 α-分泌酶 ADAM10 的表达。此外，LYC 下调小胶质细胞活化标志物 IBA-1 的表达，降低 LPS 处理小鼠的炎症介质水平并抑制氧化应激。此外，LYC 抑制 LPS 处理的 BV2 小胶质细胞中 MAPKs、NFκB 和激活的 Nrf2 信号通路的磷酸化。因此，我们的研究表明，LYC 可能通过调节 MAPKs、NFκB 和 Nrf2 信号通路改善 LPS 诱导的神经炎症、氧化应激、淀粉样蛋白形成和认知障碍，表明 LYC 可能是神经炎症相关疾病（如 AD）的一种营养预防策略。
