背景：抑郁症是一种精神障碍，以抑郁情绪甚至自杀企图作为主要临床症状，其发病机制尚未完全阐明。脑源性神经营养因子（BDNF）在抑郁症的发病机制中起着重要作用。目的：本研究的主要目的是通过调节BDNF途径评估双叶飞翼内酯（BB）干预缓解慢性不可预测轻度应激（CUMS）小鼠抑郁样行为的有效性，并揭示其潜在机制。方法：通过葡萄糖溶液偏好测试（SPT）、尾悬测验（TST）和强制游泳测试（FST）进行行为评估。CUMS小鼠随机分为5组：CUMS + 溶剂、CUMS + BB低剂量、CUMS + BB中剂量、CUMS + BB高剂量和CUMS + 氟西汀。用ELISA测定血清总肿瘤坏死因子（TNF-α）和白细胞介素6（IL-6）的水平。用西方印迹法评估小鼠海马区TNF-α、IL-6、AKT、GSK3β、β-连接蛋白、Trk-B和BDNF的蛋白表达。结果：BB治疗降低了CUMS小鼠海马区促炎细胞因子（IL-6和TNF-α）水平，并增加了BDNF蛋白的表达。此外，BB治疗增强了这些小鼠海马区BDNF受体Trk-B下游的AKT/GSK3β/β-连接蛋白信号通路。结论：总的来说，实验结果表明，BB逆转了CUMS诱导的抑郁样行为。BB通过抑制神经炎症和增强神经营养因子的功能表现出抗抑郁样效应。

Background: Depression is a psychiatric disorder with depressed mood and even suicide attempts as the main clinical symptoms, and its pathogenesis has not yet been fully elucidated. Brain derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of depression. Purpose: The main aim of the present study was to evaluate the effectiveness and reveal the potential mechanisms of bilobalide (BB) intervention in alleviating depression-like behaviors by using chronic unpredictable mild stress (CUMS) mice via mediating the BDNF pathway. Methods: Behavioral assessments were carried out by using the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). CUMS mice were randomly divided into 5 groups: CUMS + solvent, CUMS + BB low, CUMS + BB medium, CUMS + BB high and CUMS + fluoxetine. Total serum levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were measured by ELISA. Expression of TNF-α, IL-6, AKT, GSK3β, β-catenin, Trk-B and BDNF in the mouse hippocampus was assessed by western blotting. Results: BB treatment reduced the levels of pro-inflammatory cytokines (IL-6 and TNF-α) and increased the protein expression of BDNF in the hippocampus region of the CUMS mice. Moreover, BB treatment enhanced the AKT/GSK3β/β-catenin signaling pathway which is downstream of the BDNF receptor Trk-B in the hippocampus of these mice. Conclusions: Overall, the experimental results indicated that BB reverses CUMS-induced depression-like behavior. BB exerts antidepressant-like effects by inhibiting neuroinflammation and enhancing the function of neurotrophic factors.