Department of Pharmacology, Pharmacy College, Nantong University, Nantong 226001, Jiangsu, China; Provincial Key Laboratory of Inflammation and Molecular Drug Target, Nantong 226001, Jiangsu, China.
Department of Pharmacy, The First Affiliated Hospital of Soochow University, 899 PingHai Road, Suzhou 215000, Jiangsu, China.
Neurosci Lett. 2021 Jul 13;757:135994. doi: 10.1016/j.neulet.2021.135994. Epub 2021 May 29.
Current available antidepressants have various adverse reactions and slow pharmacodynamics, so it is necessary to find novel antidepressants for effective treatment. Xanthoceraside (XAN), a novel triterpenoid saponin extracted from the fruit husks of Xanthoceras sorbifolium Bunge, has anti-amnesic and neuroprotective properties. The purpose and significance of this study is to assess whether XAN has antidepressant effects in mice using the forced swim test (FST), tail suspension test (TST) and chronic unpredictable mild stress (CUMS) model of depression. The effects of XAN treatment on the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway and neurogenesis were examined. The antidepressant mechanism of XAN was explored using a BDNF inhibitor (K252a) and an anti-BDNF antibody. It was found that XAN administration significantly reversed the depressive-like behaviors of CUMS-treated mice. XAN treatment also significantly prevented the decreasing effects of CUMS on the hippocampal BDNF signaling and neurogenesis. The antidepressant effects of XAN in mice were blocked by both administration of K252a and anti-BDNF antibody. Collectively, these findings indicate that XAN possesses antidepressant effects in mice which are mediated by activation of hippocampal BDNF signaling pathway, thus providing the first evidence that XAN can be a potential antidepressant candidate.
目前可用的抗抑郁药具有各种不良反应和缓慢的药效动力学，因此有必要寻找新型抗抑郁药进行有效治疗。从文冠果果皮中提取的新型三萜皂苷——文冠果皂苷（XAN）具有抗健忘和神经保护作用。本研究的目的和意义是使用强迫游泳试验（FST）、悬尾试验（TST）和慢性不可预测轻度应激（CUMS）抑郁模型评估 XAN 是否对小鼠具有抗抑郁作用。检查了 XAN 治疗对海马脑源性神经营养因子（BDNF）信号通路和神经发生的影响。使用 BDNF 抑制剂（K252a）和抗 BDNF 抗体探索了 XAN 的抗抑郁机制。结果发现，XAN 给药可显著逆转 CUMS 处理小鼠的抑郁样行为。XAN 治疗还显著阻止了 CUMS 对海马 BDNF 信号和神经发生的降低作用。K252a 和抗 BDNF 抗体的给药均阻断了 XAN 在小鼠中的抗抑郁作用。总之，这些发现表明 XAN 对小鼠具有抗抑郁作用，其机制是通过激活海马 BDNF 信号通路介导的，这首次表明 XAN 可能成为一种潜在的抗抑郁候选药物。
