Anti-inflammatory approaches are emerging as a new strategy for the treatment of depressive disorders. Ginsenoside Rb1 (GRb1), a major component of Panax ginseng, can inhibit inflammatory cascade and alleviate depressive-like behaviors. Microglia can promote or inhibit adult hippocampal neurogenesis according to their functional phenotypes. Here, we examine whether GRb1 may exert antidepressant effects by promoting a pro-neurogenic phenotype of microglia and thereby increasing neurogenesis. The antidepressant effects of GRb1 or the licensed antidepressant imipramine (IMI) were assessed in chronic mild stress (CMS)-exposed male mice. The depressive-like behaviors of mice were evaluated by sucrose preference test, forced swimming test (FST), and tail suspension test (TST). The microglial phenotypes were identified by pro- and anti-inflammatory cytokine expression and morphological properties, analyzed by RT-qPCR, western blotting, and immunofluorescence staining. The effect of GRb1-treated microglia on adult hippocampal neurogenesis in vivo and in vitro was detected using immunofluorescence staining. Behavioral assessment indicated that GRb1 or IMI treatment alleviated depressive-like behaviors in CMS-exposed mice. Immunofluorescence examination demonstrated that GRb1 induced a pro-neurogenic phenotype of microglia via activating PPARγ in vivo and in vitro, which were effectively reversed by the PPARγ inhibitor GW9662. In addition, GRb1-treated microglia increased the proliferation and differentiation of neural precursor cells. These findings demonstrated that GRb1 alleviated depressive-like behaviors of CMS-exposed male mice mainly through PPARγ-mediated microglial activation and improvement of adult hippocampus neurogenesis.

中文翻译：

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人参皂甙 Rb1 通过 PPARγ 激活在暴露于慢性轻度压力​​的雄性小鼠中诱导神经原性小胶质细胞表型

抗炎方法正在成为治疗抑郁症的新策略。人参皂甙 Rb1 (GRb1) 是人参的主要成分，可抑制炎症级联反应并缓解抑郁样行为。小胶质细胞可根据其功能表型促进或抑制成年海马神经发生。在这里，我们检查了 GRb1 是否可以通过促进小胶质细胞的促神经源性表型从而增加神经发生来发挥抗抑郁作用。在慢性轻度应激 (CMS) 暴露的雄性小鼠中评估了 GRb1 或许可的抗抑郁药丙咪嗪 (IMI) 的抗抑郁作用。通过蔗糖偏好试验、强迫游泳试验（FST）和悬尾试验（TST）评价小鼠的抑郁样行为。通过促炎和抗炎细胞因子表达和形态学特性鉴定小胶质细胞表型，通过 RT-qPCR、蛋白质印迹和免疫荧光染色进行分析。使用免疫荧光染色检测 GRb1 处理的小胶质细胞在体内和体外对成人海马神经发生的影响。行为评估表明，GRb1 或 IMI 治疗减轻了 CMS 暴露小鼠的抑郁样行为。免疫荧光检查表明，GRb1 通过在体内和体外激活 PPARγ 诱导小胶质细胞的促神经原性表型，而 PPARγ 抑制剂 GW9662 可有效逆转这种表型。此外，GRb1 处理的小胶质细胞增加了神经前体细胞的增殖和分化。