PDF(Pubmed)
Abstract：
Post-traumatic stress disorder (PTSD) is a persistent psychiatric condition that arises following exposure to traumatic events such as warfare, natural disasters, or other catastrophic incidents, typically characterized by heightened anxiety, depressive symptoms, and cognitive dysfunction. In this study, animals subjected to single prolonged stress (SPS) were administered evodiamine (EVO) and compared to a positive control group receiving sertraline. The animals were then assessed for alterations in anxiety, depression, and cognitive function. Histological analysis was conducted to examine neuronal changes in the hippocampus. In order to predict the core targets and related mechanisms of evodiamine intervention in PTSD, network pharmacology was used. The metabolic markers pre- and post-drug administration were identified using nontargeted serum metabolomics techniques, and the intersecting Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened. Finally, the core targets were validated through molecular docking, enzyme-linked immunosorbent assays, and immunofluorescence staining to confirm the anti-PTSD effects and mechanisms of these targets. As well as improving cognitive impairment, evodiamine reversed anxiety- and depression-like behaviors. It also inhibited the reduction in the number of hippocampal neuronal cells and Nissl bodies in SPS mice inhibited angiotensin converting enzyme (ACE) levels in the hippocampus of SPS mice, and modulated the renin angiotensin pathway and its associated serum metabolites in brain tissue. Evodiamine shows promise as a potential candidate for alleviating the symptoms of post-traumatic stress disorder.
摘要：
创伤后应激障碍（PTSD）是一种持续的精神疾病，在暴露于战争等创伤事件后出现，自然灾害,或其他灾难性事件，典型的特点是焦虑加剧，抑郁症状,和认知功能障碍。在这项研究中,接受单次长期应激（SPS）的动物被给予eviodiamine（EVO），并与接受舍曲林的阳性对照组进行比较。然后评估动物的焦虑变化，抑郁症,和认知功能。进行组织学分析以检查海马中的神经元变化。为了预测吴茱萸碱干预PTSD的核心靶点和相关机制，使用网络药理学。使用非靶向血清代谢组学技术鉴定给药前和给药后的代谢标志物，并筛选了交叉的京都基因和基因组百科全书（KEGG）途径。最后,通过分子对接对核心靶标进行了验证，酶联免疫吸附测定，和免疫荧光染色以确认这些靶标的抗PTSD作用和机制。除了改善认知障碍，evodiamine逆转了焦虑和抑郁样行为。它还抑制了SPS小鼠海马神经元细胞数量的减少，Nissl体抑制了SPS小鼠海马中血管紧张素转换酶（ACE）的水平，并调节脑组织中的肾素-血管紧张素通路及其相关的血清代谢产物。伊沃二胺有望成为缓解创伤后应激障碍症状的潜在候选者。
