Xanthoceraside administration produces significant antidepressant effects in mice through activation of the hippocampal BDNF signaling pathway

Abstract

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.

Keywords: Brain-derived neurotrophic factor; Chronic unpredictable mild stress; Depression; Hippocampal neurogenesis; Xanthoceraside.