R21 Project: Curcumin Treatment of Fibrosis

描述(申请人提供)：替代医学从业者 推荐姜黄素，一种香料姜黄的成分，作为治疗 自身免疫性疾病。硬皮病是一种衰弱的自身免疫性疾病 在美国有超过10万人受到影响，其中大部分是女性。的标志 硬皮病是一种皮肤纤维化。当伴有内脏器官纤维化时， 导致严重的发病率和死亡率。尽管它的发生很普遍， 鲜为人知的是有效的治疗方法。作为我们长期计划的一部分 目的了解细胞外基质的异常调节 硬皮病中蛋白质的积累，我们处理原代成纤维细胞培养物 从硬皮病患者的肺部提取姜黄素。我们发现这个 治疗抑制了胶原蛋白的积累，促进了这些细胞的死亡 对正常肺成纤维细胞无影响。有趣的是， 姜黄素对硬皮病成纤维细胞的这些作用在 维生素C的存在如果姜黄素对硬皮病有同样的效果 体内的成纤维细胞就像它在培养中一样，那么姜黄素很可能是 治疗硬皮病的有效方法。而姜黄素还没有用于 规范的医疗实践，在中国和印度的民间医药中使用姜黄 治疗范围广泛的疾病。已发表的文章显示姜黄素有一种 一系列有效的生物活性，包括抗癌，抗炎， 和抗菌剂。姜黄素在民间医药中的使用，发表了关于 姜黄素和我们的结果相结合，表明姜黄素是无毒的， 一种已经在替代医学中使用的治疗方法，很可能 对硬皮病和其他纤维性疾病患者有明显的积极作用 疾病。 为了验证姜黄素可能是一种有益的治疗方法的假设 特别是硬皮病和纤维性疾病，我们将：1)使用 培养成纤维细胞以确定其分子和细胞机制 姜黄素对硬皮病患者细胞的特异性影响 2)我们将使用动物模型进行翻译研究 硬皮病和肺纤维化以确定姜黄素是否确实有效 在体内治疗肺纤维化。这些实验将证明 疗效及其治疗效果的科学基础 已经得到了替代医学从业者的推荐。

DESCRIPTION (provided by applicant): Practitioners of alternative medicine recommend curcumin, a component of the spice turmeric, as a treatment for autoimmune diseases. Scleroderma is a debilitating autoimmune disease that affects over 100,000 people in the US, mostly women. The hallmark of scleroderma is dermal fibrosis. When accompanied by visceral organ fibrosis, significant morbidity and mortality results. Despite its widespread occurrence, little is known to suggest effective treatment. As part of our long-term objective of understanding the aberrant regulation of extracellular matrix protein accumulation in scleroderma, we treated primary fibroblast cultures from the lungs of scleroderma patients with curcumin. We found that this treatment inhibits collagen accumulation and promotes cell death in these cultures while having no effect on normal lung fibroblasts. Interestingly, these effects of curcumin on scleroderma fibroblasts are enhanced in the presence of vitamin C. If curcumin were to have the same effect on scleroderma fibroblasts in vivo as it has in culture, then curcumin would be likely to be an effective treatment for scleroderma. While curcumin is not yet used in standard medical practice, in Chinese and Indian folk medicine turmeric is used to treat a broad range of ailments. Published articles show curcumin to have a range of potent biological activities including anticancer, anti-inflammatory, and antimicrobial. The use of curcumin in folk medicine, published studies on curcumin, and our results combine to indicate that curcumin is non-toxic and is a treatment already used in alternative medicine that is likely to have demonstrably positive effects on patients with scleroderma and other fibrotic diseases. In order to test the hypothesis that curcumin may be a beneficial treatment for scleroderma in particular and fibrotic diseases in general, we will: 1) Use cultured fibroblasts to determine the molecular and cellular mechanisms involved in the specific effects of curcumin on cells from scleroderma patients and 2) We will perform translational research using an animal model for scleroderma and lung fibrosis to determine whether curcumin is indeed effective in treating lung fibrosis in vivo. These experiments will demonstrate the efficacy and the scientific basis for that efficacy of a disease treatment already recommended by practitioners of alternative medicine.