NATURAL VITAMIN E FORMS AS ANTI-INFLAMMATORY DRUGS

天然维生素 E 形式作为抗炎药物

• 批准号: 7076096
• 负责人: Qing Jiang
• 金额: $ 32.65万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076096
• 关键词: alternative medicine; antiinflammatory agents; aspirin; combination chemotherapy; drug interactions; drug screening /evaluation; eicosanoid metabolism; eicosanoids; inflammation; laboratory rat; nonhuman therapy evaluation; nutrition related tag; oxidoreductase inhibitor; prostaglandin endoperoxide synthase; tissue /cell culture; tocopherols; vitamin therapy

DESCRIPTION (provided by applicant): Chronic inflammation constitutes one of the major etiologies of degenerative diseases including cancer, and cardiovascular and neurodegenerative diseases; chronic inflammation also contributes to rheumatoid arthritis, asthma and hepatitis. These diseases are among the leading causes of death and disability in the world. During inflammation, several pro-inflammatory mediators including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), as well as cytokines, such as TNF-alpha, play central roles in regulating inflammatory response and inflammation-mediated damage. Vitamin E comprises eight structurally related molecules, alpha-,beta-, gamma-, delta-tocopherol, and alpha-,beta-, gamma-, delta -tocotrienol. Among them, only alpha -tocopherol (alphaT) has been extensively studied. Recent studies indicate that other forms of vitamin E have unique properties, which are not shared by alphaT, but are important to human disease prevention and therapy. Gamma-Tocopherol (gammaT) and its metabolite, but not aT, exhibit anti-inflammatory effects by inhibiting cyclooxygenase (COX)- catalyzed formation of PGE2. In a rat inflammation model, gammaT inhibits not only PGE2, but also LTB4, and TNF-alpha. These results suggest that gammaT may be superior to some commonly used non-steroid anti-inflammatory drugs (NSAIDs), such as COX inhibitors, most of which only inhibit the COX-mediated pathway. Preliminary studies also indicate that delta- tocopherol and gamma-tocotrienol, compared with gammaT, are even stronger inhibitors of the COX-catalyzed formation of PGE2. These observations led to the current hypothesis that certain forms of vitamin E and their combinations have unique pharmaceutical utility as anti-inflammatory drugs, or as supplements that complement and improve current treatments for inflammatory diseases. This hypothesis will be tested by pursuit of the following Specific Aims in cell culture and animal experiments: 1. Investigate in vitro anti-inflammatory properties of individual vitamin E forms and their combinations; 2. Investigate and compare in vivo anti-inflammatory activities of individual vitamin E forms and their combinations; and 3. Investigate the potentially improved effects of combining certain forms of vitamin E and NSAIDs, such as aspirin, in a rat inflammation model. Our studies may lead to the discovery of novel and better therapy for treating and preventing inflammatory diseases, and provide the scientific rationale, the experimental evidence and the biochemical basis for future human studies.

描述（由申请人提供）：慢性炎症构成了包括癌症以及心血管和神经退行性疾病在内的退化性疾病的主要病因之一；慢性炎症也有助于类风湿关节炎，哮喘和肝炎。这些疾病是世界上死亡和残疾的主要原因之一。在炎症过程中，包括前列腺素E2（PGE2）和白三烯B4（LTB4）以及TNF-α等细胞因子在内的几种促炎性介质在调节炎症反应和炎症介导的损伤中起着核心作用。维生素E包含八个结构相关的分子，α-，β-，伽马 - - 生育酚和α-，β-，γ-，delta -tocotrienol。其中，仅对α-生育酚（Alphat）进行了广泛的研究。最近的研究表明，其他形式的维生素E具有独特的特性，这不是Alphat共享的，但对预防人类疾病和治疗很重要。 γ-生育酚（Gammat）及其代谢产物，但没有通过抑制环氧酶（COX） - PGE2的催化形成表现出抗炎作用。在大鼠炎症模型中，γ不仅抑制PGE2，还抑制LTB4和TNF-Alpha。这些结果表明，γ可能优于一些常用的非类固醇抗炎药（NSAIDS），例如Cox抑制剂，其中大多数仅抑制COX介导的途径。初步研究还表明，与γ相比，三角洲 - 生育酚和伽马 - 牛皮林酚是PGE2的Cox催化形成的更强抑制剂。这些观察结果导致了当前的假设，即某些形式的维生素E及其组合具有独特的药物效用，作为抗炎药，或作为补充并改善炎症性疾病治疗的补充剂。该假设将通过追求细胞培养和动物实验的以下特定目的来检验：1。研究单个维生素E及其组合的体外抗炎特性； 2。调查并比较单个维生素E及其组合的体内抗炎活性；和3。研究在大鼠炎症模型中结合某些形式的维生素E和NSAID（例如阿司匹林）的可能改善的影响。我们的研究可能导致发现新颖和更好的治疗疗法，以治疗和预防炎症性疾病，并提供科学原理，实验证据和未来人类研究的生化基础。

项目成果

In vitro stable isotope labeling for discovery of novel metabolites by liquid chromatography-mass spectrometry: Confirmation of gamma-tocopherol metabolism in human A549 cell.

• DOI: 10.1016/j.chroma.2009.12.002
• 发表时间: 2010-01-29
• 期刊: Journal of chromatography. A
• 作者: Yang WC;Regnier FE;Jiang Q;Adamec J
• 通讯作者: Adamec J

A combination of aspirin and gamma-tocopherol is superior to that of aspirin and alpha-tocopherol in anti-inflammatory action and attenuation of aspirin-induced adverse effects.

• DOI: 10.1016/j.jnutbio.2008.08.004
• 发表时间: 2009-11
• 期刊: JOURNAL OF NUTRITIONAL BIOCHEMISTRY
• 影响因子: 5.6
• 作者: Jiang, Qing;Moreland, Michelle;Ames, Bruce N.;Yin, Xinmin
• 通讯作者: Yin, Xinmin

Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively.

• DOI: 10.4049/jimmunol.1002342
• 发表时间: 2011-01-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Jiang Z;Yin X;Jiang Q
• 通讯作者: Jiang Q

Gamma-tocotrienol induces apoptosis and autophagy in prostate cancer cells by increasing intracellular dihydrosphingosine and dihydroceramide.

• DOI: 10.1002/ijc.26054
• 发表时间: 2012-02-01
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Jiang, Qing;Rao, Xiayu;Kim, Choon Young;Freiser, Helene;Zhang, Qingbo;Jiang, Ziying;Li, Guilan
• 通讯作者: Li, Guilan