Fang Ke, Li Hua-Rong, Chen Xing-Xing, Gao Xin-Ran, Huang Ling-Ling, Du An-Qi, Jiang Chuan, Li Hua, Ge Jin-Fang
School of Pharmacy, Anhui Medical University, Hefei, China.
Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, China.
Front Pharmacol. 2020 Jan 17;10:1544. doi: 10.3389/fphar.2019.01544. eCollection 2019.
Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.
槲皮素是一种具有多种生物活性的多酚，我们的初步研究结果表明，它可以缩短小鼠在强迫游泳试验和尾悬试验中的不动时间。本研究的目的是探讨其对脂多糖（LPS）攻击大鼠行为表现的影响，并探索潜在机制。结果表明，灌胃给予槲皮素（40mg/kg）可改善LPS攻击大鼠的体重增加，增加糖精偏好试验中的糖精偏好指数和Y迷宫中的新臂偏好指数，并减少强迫游泳试验中的不动时间。然而，它对LPS攻击大鼠在莫里斯水迷宫中的表现以及nesfatin-1、C反应蛋白（CRP）和白细胞介素-6的血浆浓度没有显著影响。蛋白质印迹结果表明，LPS攻击大鼠的海马体和前额叶皮质（PFC）中脑源性神经营养因子（BDNF）、Copine 6、磷酸化酪氨酸激酶B（p-TrkB）和髓样细胞上表达的触发受体（TREM）1的表达水平均降低，而TREM2的表达增加。海马体中突触素-1的蛋白表达降低，而PFC中无显著变化。这些蛋白质表达的失衡可以通过槲皮素治疗来平衡。结果表明，槲皮素可以减轻LPS诱导的大鼠抑郁样行为和学习记忆障碍，其机制可能与调节海马体和PFC中Copine 6和TREM1/2与BDNF相关的失衡表达有关。
