Department of Laboratory Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, 225012, Jiangsu, China.
Department of Medicine, Yangzhou University, Yangzhou, 225012, Jiangsu, China.
Mol Neurobiol. 2024 Sep;61(9):6628-6641. doi: 10.1007/s12035-024-03926-x. Epub 2024 Feb 8.
Cognitive dysfunction was a common symptom of major depressive disorder (MDD). In previous studies, psychological stress leads to activation and proliferation of microglial cells in different brain regions. Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. To demonstrate the role of quercetin in the hippocampal inflammatory response in depress mice. The chronic unpredictable stress (CUS) depressive mice model built is used to explore the protective effects of quercetin on depression. Neurobehavioral test, protein expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and heat shock protein 90 (HSP90), and cytokines (IL-6, IL-1β, MCP-1, and TNF-α) were assessed. Quercetin ameliorated depressive-like behavior and cognitive impairment, and quercetin attenuates neuroinflammation and by targeting HSP90 to inhibit NLRP3 inflammasome activation. Quercetin inhibited the increase of HSP90 levels in the hippocampus and reverses inflammation-induced cognitive impairment. Besides, quercetin inhibited the increased level of cytokines (IL-6, IL-1β, MCP-1, and TNF-α) in the hippocampus of the depressive model mouse and the increased level of cytokines (IL-6, IL-1β, and MCP-1) in microglia. The current study indicated that quercetin mitigated depressive-like behavior and by targeting HSP90 to inhibit NLRP3 inflammasome activation in microglia and depressive mice model, meanwhile ameliorated cognitive impairment in depression. Quercetin has huge potential for the novel pharmacological efficacy of antidepressant therapy.
认知功能障碍是重性抑郁障碍（MDD）的常见症状。在以前的研究中，心理应激会导致不同脑区的小胶质细胞激活和增殖。槲皮素是一种从蔬菜和水果中提取的生物类黄酮，在各种疾病中具有抗炎作用。为了证明槲皮素在抑郁小鼠海马炎症反应中的作用，构建了慢性不可预测应激（CUS）抑郁小鼠模型，以探索槲皮素对抑郁的保护作用。通过神经行为测试、NOD 样受体热蛋白结构域相关蛋白 3（NLRP3）和热休克蛋白 90（HSP90）的蛋白表达以及细胞因子（IL-6、IL-1β、MCP-1 和 TNF-α）来评估。槲皮素改善了抑郁样行为和认知障碍，槲皮素通过靶向 HSP90 抑制 NLRP3 炎性小体激活来减轻神经炎症。槲皮素抑制了海马中 HSP90 水平的升高，并逆转了炎症引起的认知障碍。此外，槲皮素抑制了抑郁模型小鼠海马中细胞因子（IL-6、IL-1β、MCP-1 和 TNF-α）水平的升高和小胶质细胞中细胞因子（IL-6、IL-1β 和 MCP-1）水平的升高。本研究表明，槲皮素通过靶向 HSP90 抑制小胶质细胞和抑郁模型小鼠中 NLRP3 炎性小体的激活，减轻了抑郁样行为，同时改善了抑郁中的认知障碍。槲皮素在抗抑郁治疗的新的药理学疗效方面具有巨大的潜力。
