Botanicals for Treatment of Depression

治疗抑郁症的植物药

• 批准号: 7140056
• 负责人: Gregory R. J Thatcher
• 金额: $ 18.5万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2008-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140056
• 关键词: amygdala; antidepressants; behavior test; behavioral /social science research tag; biochemistry; biological signal transduction; biomarker; biomimetics; cyclic GMP; depression; disease /disorder model; estradiol; estrogens; hippocampus; immunocytochemistry; laboratory rat; nitric oxide; phosphorylation; phytoestrogens; plant extracts; protein localization

DESCRIPTION (provided by applicant): Depression affects more than 17% of the overall population, with prevalence in women twice that in men. Estrogen treatment has been shown to result in elevation of mood, and botanicals, in particular from black cohosh (Actaea racemosa; AR), and red clover (Trifolium pretense; TP), have been reported to manifest antiestrogenic, estrogenic, and serotonergic activity. Botanicals may be proven as alternatives for hormone replacement therapy (HRT) and selective estrogen receptor modulator (SERM) therapy, which is needed given the health risks that are being increasingly associated with these therapies. The data from clinical trials on botanicals testing the benefits in menopausal complaints, including depression, is ambiguous. Unfortunately, whereas estrogens and SERMs have been well studied in a wide variety of animal models, such studies are relatively lacking on botanicals. It is the objective of this project to obtain convincing animal model data on the antidepressant activity of botanicals and to elucidate the biochemical pathways involved, in order to determine a basis for clinical studies. The central hypothesis of this proposal is that the antidepressant activity of estrogen, phytoestrogens, TP and AR botanicals is mediated at least in part via NO/cGMP signalling in the hippocampus and amygdala. It is an objective of this proposal to test this hypothesis by comparison of estrogen, botanicals and NO mimetics in an animal behavioural model and by immunocytochemistry directed at selected protein biomarkers associated with signaling cascades. Observations on the location and elevation of levels of selected proteins in amygdala and hippocampus will identify changes characteristic of antidepressant activity. A long term goal of the project, is the development of an in vitro screen for identifying antidepressant botanicals.

描述（由申请人提供）：抑郁症影响着总人口的 17% 以上，女性患病率是男性的两倍。雌激素治疗已被证明可以提高情绪，据报道，植物药，特别是黑升麻（Actaearacemosa；AR）和红三叶草（Trifolium pretense；TP），具有抗雌激素、雌激素和血清素活性。植物药可能被证明可以作为激素替代疗法（HRT）和选择性雌激素受体调节剂（SERM）疗法的替代品，考虑到与这些疗法越来越相关的健康风险，这是必要的。测试植物药对更年期疾病（包括抑郁症）益处的临床试验数据尚不明确。不幸的是，尽管雌激素和 SERM 在多种动物模型中得到了充分研究，但对植物药的研究相对缺乏。该项目的目的是获得有关植物药抗抑郁活性的令人信服的动物模型数据，并阐明所涉及的生化途径，以确定临床研究的基础。该提议的中心假设是，雌激素、植物雌激素、TP 和 AR 植物药的抗抑郁活性至少部分是通过海马和杏仁核中的 NO/cGMP 信号传导介导的。本提案的目的是通过在动物行为模型中比较雌激素、植物药和 NO 模拟物以及针对与信号级联相关的选定蛋白质生物标志物进行免疫细胞化学来检验这一假设。对杏仁核和海马中选定蛋白质的位置和水平升高的观察将确定抗抑郁活性的变化特征。该项目的长期目标是开发用于鉴定抗抑郁植物药的体外筛选。

项目成果

NO-SSRIs: Nitric Oxide Chimera Drugs Incorporating a Selective Serotonin Reuptake Inhibitor.

• DOI: 10.1021/ml2000033
• 发表时间: 2011-09-08
• 期刊: ACS MEDICINAL CHEMISTRY LETTERS
• 影响因子: 4.2
• 作者: Abdul-Hay, Samer;Schiefer, Isaac T.;Chandrasena, R. Esala P.;Li, Min;Abdelhamid, Ramy;Wang, Yue-Ting;Tavassoli, Ehsan;Michalsen, Bradley;Asghodom, Rezene T.;Luo, Jia;Thatcher, Gregory R. J.
• 通讯作者: Thatcher, Gregory R. J.