Previous studies reported that ginsenoside Rg1 (Rg1) exerts antidepressant-like effect in animal models of depression. However, its effect on post-traumatic stress disorder (PTSD) remains elusive; PTSD is a common and costly psychiatric condition with negative cognitive and affective dysfunctions, such as anxiety and depression. In this study, we evaluated the role of Rg1 in a validated mice model of PTSD induced by single-prolonged stress (SPS). Sertraline, one of the FDA-approved medications for PTSD was used as a positive control. Our results showed that SPS exposure led to increased anxiety-like and despair-like behaviors. SPS exposure also caused enhanced contextual fear memory and overgeneralization of learned fear. Sertraline significantly ameliorated those abnormal behaviors induced by SPS, while Rg1 did not. Meanwhile, we found that sertraline but not Rg1 blocked the suppressive effect of SPS on adult neurogenesis in the hippocampus. Consistently, we found that SPS elevated adrenocorticotropic hormone (ACTH) level in the serum, which was inhibited by sertraline but not Rg1. Our results thus demonstrate that Rg1 at a dose used to treat depression may not be effective to rescue behavioral deficits associated with PTSD.

先前的研究报道了人参皂苷Rg1（Rg1）在抑郁症动物模型中具有抗抑郁样作用。然而，它对创伤后应激障碍（PTSD）的影响仍然难以捉摸。PTSD是一种常见且代价高昂的精神疾病，具有负面的认知和情感功能障碍，例如焦虑和抑郁。在这项研究中，我们评估了Rg1在单持续应激（SPS）诱导的PTSD验证小鼠模型中的作用。舍曲林是FDA批准的PTSD药物之一，被用作阳性对照。我们的结果表明，SPS暴露导致焦虑和绝望行为增加。SPS暴露还导致增强的上下文恐惧记忆和对学习到的恐惧的过度概括。舍曲林可明显改善SPS引起的异常行为，而Rg1则不能。与此同时，我们发现舍曲林而非Rg1阻止了SPS对海马成年神经发生的抑制作用。一致地，我们发现SPS升高了血清中的促肾上腺皮质激素（ACTH）水平，这被舍曲林抑制，但未被Rg1抑制。因此，我们的结果证明，用于治疗抑郁症的剂量的Rg1可能无法有效挽救与PTSD相关的行为缺陷。