Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Department of Agronomy, Research Institute of Life Science, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Mol Neurobiol. 2019 Jan;56(1):671-687. doi: 10.1007/s12035-018-1101-1. Epub 2018 May 19.
Microglia plays a critical role in the brain and protects neuronal cells from toxins. However, over-activation of microglia leads to deleterious effects. Lipopolysaccharide (LPS) has been reported to affect neuronal cells via activation of microglia as well as directly to initiate neuroinflammation. In the present study, we evaluated the anti-inflammatory and anti-oxidative effect of anthocyanins against LPS-induced neurotoxicity in an animal model and in cell cultures. Intraperitoneal injections of LPS (250 μg/kg/day for 1 week) induce ROS production and promote neuroinflammation and neurodegeneration which ultimately leads to memory impairment. However, anthocyanins treatment at a dose of 24 mg/kg/day for 2 weeks (1 week before and 1 week co-treated with LPS) prevented ROS production, inhibited neuroinflammation and neurodegeneration, and improved memory functions in LPS-treated mice. Both histological and immunoblot analysis indicated that anthocyanins reversed the activation of JNK, prevented neuroinflammation by lowering the levels of inflammatory markers (p-NF-kB, TNF-α, and IL-1β), and reduced neuronal apoptosis by reducing the expression of Bax, cytochrome c, cleaved caspase-3, and cleaved PARP-1, while increasing the level of survival proteins p-Akt, p-GSK3β, and anti-apoptotic Bcl-2 protein. Anthocyanins treatment increased the levels of memory-related pre- and post-synaptic proteins and improved the hippocampus-dependent memory in the LPS-treated mice. Overall, this data suggested that consumption of naturally derived anti-oxidant agent such as anthocyanins ameliorated several pathological events in the LPS-treated animal model and we believe that anthocyanins would be a safe therapeutic agent for slowing the inflammation-induced neurodegeneration in the brain against several diseases such as Alzheimer's disease and Parkinson's disease.
小胶质细胞在大脑中起着至关重要的作用，可保护神经元细胞免受毒素侵害。然而，小胶质细胞的过度激活会导致有害影响。脂多糖（LPS）已被报道通过激活小胶质细胞以及直接引发神经炎症来影响神经元细胞。在本研究中，我们评估了花青素对 LPS 诱导的动物模型和细胞培养物中神经毒性的抗炎和抗氧化作用。腹腔内注射 LPS（250μg/kg/天，持续 1 周）会导致 ROS 产生，并促进神经炎症和神经退行性变，最终导致记忆障碍。然而，花青素以 24mg/kg/天的剂量治疗 2 周（1 周前和 1 周与 LPS 共同治疗）可防止 ROS 产生，抑制神经炎症和神经退行性变，并改善 LPS 处理小鼠的记忆功能。组织学和免疫印迹分析表明，花青素逆转了 JNK 的激活，通过降低炎症标志物（p-NF-kB、TNF-α 和 IL-1β）的水平来预防神经炎症，并通过降低 Bax、细胞色素 c、裂解 caspase-3 和裂解 PARP-1 的表达来减少神经元凋亡，同时增加存活蛋白 p-Akt、p-GSK3β 和抗凋亡 Bcl-2 蛋白的水平。花青素治疗增加了与记忆相关的前突触和后突触蛋白的水平，并改善了 LPS 处理小鼠的海马依赖记忆。总体而言，这些数据表明，消耗天然抗氧化剂如花青素可改善 LPS 处理动物模型中的几种病理事件，我们相信花青素将成为一种安全的治疗剂，可减缓几种疾病（如阿尔茨海默病和帕金森病）中炎症诱导的大脑神经退行性变。
