Wang Xinxin, Weng Guangdong, Gao Yunpei, Wang Yu, Zhang Chengxin
Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
University of Science and Technology of China, Hefei, Anhui, China.
Psychopharmacology (Berl). 2025 Apr 10. doi: 10.1007/s00213-025-06784-0.
Quercetin is a natural flavonoid which has been shown to exhibit anti-inflammatory and anxiolytic properties. Neuroinflammation has recently been identified as a major cause of anxiety disorders. Both the lateral hypothalamus (LH) and bed nucleus of the stria terminalis (BNST) are important brain regions that regulate anxiety. This study aims to explore the effect of quercetin on anxiety-like behaviors, as well as the underlying mechanisms associated with neuroinflammation in the LH and BNST.
The anxiety models were established in male mice by chronic restraint stress (CRS) and lipopolysaccharide (LPS) administration. The elevated plus maze (EPM) and open field (OF) tests were used to evaluate anxiety level. Immunofluorescent staining and quantitative real-time PCR were performed to examine the expression of microglia and inflammatory cytokines in the LH and BNST of male mice.
Behavioral data showed that quercetin treatment in male mice significantly alleviated anxiety in the EPM and OF tests. Examination of the inflammation level further revealed that quercetin administration significantly inhibited microglia activation in the LH and BNST of CRS- and LPS-treated male mice, while concurrently reducing the levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the LH of CRS-treated male mice, as well as interleukin-1β (IL-1β) mRNA expression in the LH of LPS-treated male mice. Furthermore, we found that the expression of NF-κB was downregulated by quercetin in the LH of CRS-treated male mice.
Our study indicates the clinical potential of quercetin in neuroinflammation-related anxiety, and begins to show that the underlying mechanism in the chronic restraint stress condition may potentially involve the modulation of NF‑κB signaling pathway in the LH.
槲皮素是一种天然黄酮类化合物，已被证明具有抗炎和抗焦虑特性。神经炎症最近被确定为焦虑症的主要原因。下丘脑外侧区（LH）和终纹床核（BNST）都是调节焦虑的重要脑区。本研究旨在探讨槲皮素对焦虑样行为的影响，以及与LH和BNST中神经炎症相关的潜在机制。
通过慢性束缚应激（CRS）和注射脂多糖（LPS）在雄性小鼠中建立焦虑模型。采用高架十字迷宫（EPM）和旷场试验（OF）评估焦虑水平。进行免疫荧光染色和定量实时PCR检测雄性小鼠LH和BNST中小胶质细胞和炎性细胞因子的表达。
行为学数据显示，槲皮素处理可显著减轻雄性小鼠在EPM和OF试验中的焦虑。炎症水平检测进一步表明，给予槲皮素可显著抑制CRS和LPS处理的雄性小鼠LH和BNST中小胶质细胞的激活，同时降低CRS处理的雄性小鼠LH中促炎细胞因子白细胞介素-6（IL-6）的水平，以及LPS处理的雄性小鼠LH中白细胞介素-1β（IL-1β）mRNA的表达。此外，我们发现槲皮素可下调CRS处理的雄性小鼠LH中NF-κB的表达。
我们的研究表明槲皮素在神经炎症相关焦虑方面具有临床应用潜力，并初步表明在慢性束缚应激条件下其潜在机制可能涉及对LH中NF-κB信号通路的调节。
