Botanicals for Treatment of Depression

描述(申请人提供)：抑郁症影响总人口的17%以上，女性的患病率是男性的两倍。雌激素治疗已被证明可以提高情绪，植物类药物，特别是从黑升麻(Actaea racemosa；AR)和红三叶草(Trifolium prepremum；TP)中提取的植物化合物，已被报道具有抗雌激素、雌激素和5-羟色胺能活性。植物药可能被证明是激素替代疗法(HRT)和选择性雌激素受体调节剂(SERM)疗法的替代品，鉴于这些疗法日益相关的健康风险，这是必要的。测试包括抑郁症在内的更年期疾病益处的植物药物临床试验的数据并不明确。不幸的是，虽然雌激素和SERM已经在各种动物模型中得到了很好的研究，但在植物学上这类研究相对较少。本项目的目的是获得令人信服的植物抗抑郁活性的动物模型数据，并阐明其中涉及的生化途径，以确定临床研究的基础。这一建议的中心假设是，雌激素、植物雌激素、TP和AR植物类药物的抗抑郁活性至少部分是通过海马体和杏仁核中的NO/cGMP信号介导的。这项提议的目的是通过在动物行为模型中比较雌激素、植物药物和NO模拟物，以及通过针对与信号级联相关的选定蛋白质生物标志物的免疫细胞化学来验证这一假说。观察杏仁核和海马体中选定蛋白质的位置和水平的升高，将确定抗抑郁活性的变化特征。该项目的一个长期目标是开发一种用于鉴定抗抑郁植物药的体外筛选。

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.