{"title":"草药配方提取物在创伤后应激障碍小鼠模型中通过调节髓鞘蛋白/Dab-1通路改善焦虑和认知障碍","authors":"Hee Ra Park, Mudan Cai, Eun Jin Yang","doi":"10.3390/pharmaceutics16091150","DOIUrl":null,"url":null,"abstract":"We investigated the effects of epigenetic modifications on post-traumatic stress disorder (PTSD) using a novel combination of herbal medicines from Panax ginseng, Astragalus membranaceus, Atractylodes macrocephala, and Glycyrrhiza uralensis. The herbal formula extract (HFE) (250 mg/kg) was administered orally once daily for 14 days to determine its effects on PTSD in mice by combining prolonged stress and foot shock. The open field and Y-maze tests determined the effect of HFE on PTSD-induced anxiety and cognition. Hippocampal neuronal plastic changes and molecular mechanism were verified. Treatment with HFE decreased anxiety-like behavior and enhanced cognition. Moreover, it reduced the number of PTSD-related hilar ectopic granule cells in the dentate gyrus (DG). PTSD mice showed reduced neuronal plasticity of doublecortin+ cells in the DG, which was restored by HFE treatment. HFE reversed PTSD-induced inhibition of the Reelin/Dab1 pathway, a critical signaling cascade involved in brain development, and regulated Reelin methylation. Furthermore, DNA methylation, methyl-CpG binding protein 2, and DNA methyltransferase 1, which were elevated in the hippocampus of PTSD mice, were restored following HFE treatment. HFE increased the expression of synaptic plasticity-related factors in the hippocampus of PTSD mice. Our findings suggest that HFE can facilitate PTSD treatment by alleviating behavioral abnormalities through the restoration of hippocampal dysfunction via regulation of the Reelin/Dab-1 pathway and DNA methylation in the hippocampus.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Herbal Formula Extract Ameliorates Anxiety and Cognitive Impairment via Regulation of the Reelin/Dab-1 Pathway in a Murine Model of Post-Traumatic Stress Disorder\",\"authors\":\"Hee Ra Park, Mudan Cai, Eun Jin Yang\",\"doi\":\"10.3390/pharmaceutics16091150\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"We investigated the effects of epigenetic modifications on post-traumatic stress disorder (PTSD) using a novel combination of herbal medicines from Panax ginseng, Astragalus membranaceus, Atractylodes macrocephala, and Glycyrrhiza uralensis. The herbal formula extract (HFE) (250 mg/kg) was administered orally once daily for 14 days to determine its effects on PTSD in mice by combining prolonged stress and foot shock. The open field and Y-maze tests determined the effect of HFE on PTSD-induced anxiety and cognition. Hippocampal neuronal plastic changes and molecular mechanism were verified. Treatment with HFE decreased anxiety-like behavior and enhanced cognition. Moreover, it reduced the number of PTSD-related hilar ectopic granule cells in the dentate gyrus (DG). PTSD mice showed reduced neuronal plasticity of doublecortin+ cells in the DG, which was restored by HFE treatment. HFE reversed PTSD-induced inhibition of the Reelin/Dab1 pathway, a critical signaling cascade involved in brain development, and regulated Reelin methylation. Furthermore, DNA methylation, methyl-CpG binding protein 2, and DNA methyltransferase 1, which were elevated in the hippocampus of PTSD mice, were restored following HFE treatment. HFE increased the expression of synaptic plasticity-related factors in the hippocampus of PTSD mice. Our findings suggest that HFE can facilitate PTSD treatment by alleviating behavioral abnormalities through the restoration of hippocampal dysfunction via regulation of the Reelin/Dab-1 pathway and DNA methylation in the hippocampus.\",\"PeriodicalId\":19894,\"journal\":{\"name\":\"Pharmaceutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-08-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/pharmaceutics16091150\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/pharmaceutics16091150","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
我们研究了表观遗传修饰对创伤后应激障碍(PTSD)的影响,研究采用了人参、黄芪、白术和甘草的新型中药组合。小鼠口服中药配方提取物(HFE)(250 毫克/千克),每天一次,连续 14 天,通过长时间应激和足部冲击来确定其对创伤后应激障碍的影响。开阔地试验和Y-迷宫试验确定了HFE对创伤后应激障碍引起的焦虑和认知的影响。研究还验证了海马神经元的可塑性变化和分子机制。使用HFE治疗可减少焦虑样行为并提高认知能力。此外,它还减少了齿状回(DG)中与创伤后应激障碍相关的希氏异位颗粒细胞的数量。创伤后应激障碍小鼠的齿状回(DG)中双皮质素+细胞的神经元可塑性降低,而HFE治疗可恢复这种可塑性。HFE逆转了PTSD诱导的Reelin/Dab1通路抑制(Reelin/Dab1通路是参与大脑发育的关键信号级联),并调节了Reelin甲基化。此外,PTSD 小鼠海马中升高的 DNA 甲基化、甲基-CpG 结合蛋白 2 和 DNA 甲基转移酶 1 也在 HFE 治疗后得到恢复。HFE 增加了创伤后应激障碍小鼠海马中突触可塑性相关因子的表达。我们的研究结果表明,HFE可通过调节海马中的Reelin/Dab-1通路和DNA甲基化来恢复海马功能障碍,从而缓解行为异常,从而促进创伤后应激障碍的治疗。
Herbal Formula Extract Ameliorates Anxiety and Cognitive Impairment via Regulation of the Reelin/Dab-1 Pathway in a Murine Model of Post-Traumatic Stress Disorder
We investigated the effects of epigenetic modifications on post-traumatic stress disorder (PTSD) using a novel combination of herbal medicines from Panax ginseng, Astragalus membranaceus, Atractylodes macrocephala, and Glycyrrhiza uralensis. The herbal formula extract (HFE) (250 mg/kg) was administered orally once daily for 14 days to determine its effects on PTSD in mice by combining prolonged stress and foot shock. The open field and Y-maze tests determined the effect of HFE on PTSD-induced anxiety and cognition. Hippocampal neuronal plastic changes and molecular mechanism were verified. Treatment with HFE decreased anxiety-like behavior and enhanced cognition. Moreover, it reduced the number of PTSD-related hilar ectopic granule cells in the dentate gyrus (DG). PTSD mice showed reduced neuronal plasticity of doublecortin+ cells in the DG, which was restored by HFE treatment. HFE reversed PTSD-induced inhibition of the Reelin/Dab1 pathway, a critical signaling cascade involved in brain development, and regulated Reelin methylation. Furthermore, DNA methylation, methyl-CpG binding protein 2, and DNA methyltransferase 1, which were elevated in the hippocampus of PTSD mice, were restored following HFE treatment. HFE increased the expression of synaptic plasticity-related factors in the hippocampus of PTSD mice. Our findings suggest that HFE can facilitate PTSD treatment by alleviating behavioral abnormalities through the restoration of hippocampal dysfunction via regulation of the Reelin/Dab-1 pathway and DNA methylation in the hippocampus.
PharmaceuticsPharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍:
Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.