Abstract：
Evidence exists suggesting the anti-depressive activities of geniposide (GP), a major compound in Gardenia jasminoides Ellis. Accordingly, the present study attempts to explore the anti-depressive mechanism of GP in chronic unpredictable mild stress (CUMS)-induced depression-like behaviors of mice. CUMS-induced mice were given GP daily and subjected to behavioral tests to observe the effect of GP on the depression-like behaviors. It was noted that GP administration reduced depression-like behaviors in CUMS mice. Transcriptome sequencing was conducted in three control and three CUMS mice. Differentially expressed circRNAs, lncRNAs and mRNAs were then screened by bioinformatics analyses. Intersection analysis of the transcriptome sequencing results with the bioinformatics analysis results was followed to identify the candidate targets. We found that Gata2 alleviated depression-like behaviors via the metabolism- and synapse-related pathways. Gata2 was a target of miR-25-3p, which had binding sites to circ_0008405 and Oip5os1. circ_0008405 and Oip5os1 competitively bound to miR-25-3p to release the expression of Gata2. GP administration ameliorated depression-like behaviors in CUMS mice through regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks. Taken together, GP may exert a potential antidepressant-like effect on CUMS mice, which is ascribed to regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks.
摘要：
有证据表明栀子苷(GP)具有抗抑郁活性，栀子的主要化合物。因此，本研究试图探讨GP在慢性不可预知轻度应激（CUMS）诱导的小鼠抑郁样行为中的抗抑郁机制。CUMS诱导的小鼠每天给予GP并进行行为测试以观察GP对抑郁样行为的影响。注意到GP给药减少了CUMS小鼠的抑郁样行为。在三只对照和三只CUMS小鼠中进行转录组测序。差异表达的circRNAs，然后通过生物信息学分析筛选lncRNAs和mRNAs。随后将转录组测序结果与生物信息学分析结果进行交叉分析以鉴定候选靶标。我们发现Gata2通过代谢和突触相关途径减轻抑郁样行为。Gata2是miR-25-3p的靶标，其具有与circ_0008405和Oip5os1的结合位点。circ_0008405和Oip5os1竞争性结合miR-25-3p以释放Gata2的表达。GP给药通过调节circ_0008405/miR-25-3p/Gata2和Oip5os1/miR-25-3p/Gata2串扰网络改善了CUMS小鼠的抑郁样行为。一起来看,GP可能对CUMS小鼠发挥潜在的抗抑郁作用，这归因于circ_0008405/miR-25-3p/Gata2和Oip5os1/miR-25-3p/Gata2串扰网络的调节。
