Stable, antiinflammatory isothiocyanates from moringa may prevent and treat IBD

辣木中稳定的抗炎异硫氰酸盐可以预防和治疗 IBD

• 批准号: 9123529
• 负责人: Youjin Kim
• 金额: $ 7.11万
• 依托单位: NUTRASORB, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9123529
• 关键词: Acute; Affect; Africa; Anti-Inflammatory Agents; Anti-inflammatory; Apoptosis; Area; Asia; Biological Availability; Blood; Botanicals; Brassicaceae; Broccoli - dietary; Caco-2 Cells; California; Cell Cycle Arrest; Cell model; Chemicals; Chemoprotective Agent; Chronic; Chronic Disease; Cleaved cell; Climate; Clinical; Collaborations; Data; Diet; Digestion; Disease; Edible Plants; Enterocytes; Enzymes; Epithelial; Excision; Family; Feces; Food; Geographic Locations; Glucosinolates; Goals; Hawaii; Health; High Fat Diet; Human; In Vitro; Individual; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Intervention; Intestines; Isothiocyanates; Laboratories; Link; MAP Kinase Gene; Malignant Neoplasms; Mechanics; Medicine; Metabolic Biotransformation; Methods; Moringa; Moringa oleifera; Mus; Myrosinase; Natural Products; Nutrient; Nutritional; Oral; PTGS2 gene; Pathway interactions; Personal Satisfaction; Pharmacodynamics; Phase; Plant Leaves; Plants; Powder dose form; Preparation; Prevention; Procedures; Process; Property; Publishing; Rattus; Reaction; Reporting; Research; Risk; Side; Skeletal Myoblasts; Skeleton; Small Business Innovation Research Grant; Small Intestines; Sodium Dextran Sulfate; Sulforaphane; TNF gene; Taste Perception; Technology; Thiocyanates; Tissues; Toxic effect; Toxicology; Traditional Medicine; Ulcerative Colitis; Universities; Vitamins; Weight; Wistar Rats; Work; Zambia; acute toxicity; analog; aqueous; commercialization; cost efficient; cruciferous vegetable; cytotoxicity; design; experience; feeding; in vitro Model; in vivo Model; inflammatory marker; innovation; large scale production; mouse model; novel; novel strategies; prevent; product development; sugar; validation studies

 DESCRIPTION (provided by applicant): This Phase I SBIR project aims to preclinically characterize an innovative and proprietary botanical product targeting chronic inflammatory conditions such as inflammatory bowel disease (IBD). Our objective is to provide experimental support for the hypothesis that anti-inflammatory isothiocyanates (ITCs) naturally produced in the edible leaves of Moringa oleifera Lam. (moringa) after mechanical wounding provide stable, highly efficacious and practical alternatives to instable and volatile ITCs produced by plants of the crucifer family (Brassicaceae), such as broccoli. Moringa leaves are historically used as a nutritious food and traditional medicine throughout South Asia and Africa. They contain high levels of nutrients, vitamins, and beneficial phytoactives. These phytoactives include unique, sugar-modified aromatic glucosinolates that can be converted to bioactive and stable moringa isothiocyanates (MICs) in wounded leaves. We have developed a novel, simple and proprietary aqueous extraction/biotransformation method, which effectively converts moringa glucosinolates into MICs resulting in good-tasting, shelf-stable, food-grade, moringa concentrate (MC) containing at least 3% of MICs. Preliminary studies have shown that MICs equal or exceed the bioactivity of sulforaphane, a well-known ITC from broccoli. Both MC and MICs strongly reduced the expression and levels of inflammatory markers, such as iNOS, IL- 1ß, and TNF in in vitro models as well TNF levels in intestinal tissue and feces of mice fed a high fat diet. The proposed work, carried out in close collaboration with the laboratory of Dr. Ilya Raskin of Rutgers University (a leading expert in botanicals and inflammation) and three consultants, experienced in various aspects of natural products and IBD, will assess bioavailability and toxicology of MICs delivered in MC. We will further investigate anti-inflammatory effects of MC and MICs in an in vitro Caco-2 cell model with the goal of elucidating the mechanism of action of MICs and study the effects of MC in the dextran sodium-sulfate (DSS)-induced mouse model of acute and chronic ulcerative colitis. Finally, we will investigate and compare MIC content of various moringa cultivars growing in diverse climatic and geographic regions and define and optimize commercial scale MC manufacturing methods, such as wounding, residue removal and drying.

 描述（由申请人提供）：该 I 期 SBIR 项目旨在临床前表征一种针对炎症性肠病 (IBD) 等慢性炎症性疾病的创新型专有植物产品。我们的目标是为辣木可食用叶子中天然产生抗炎异硫氰酸盐 (ITC) 的假设提供实验支持。机械损伤后，辣木为十字花科植物（十字花科）（如西兰花）产生的不稳定和挥发性 ITC 提供了稳定、高效和实用的替代品。辣木叶历来在整个南亚和非洲被用作营养食品和传统药物。它们含有高含量的营养物质、维生素和有益的植物活性物质。这些植物活性物质包括独特的糖改性芳香芥子油苷，可以在受伤的叶子中转化为具有生物活性和稳定的辣木异硫氰酸酯 (MIC)。我们开发了一种新颖、简单且专有的水提取/生物转化方法，可有效地将辣木芥子油苷转化为 MIC，从而产生口感好、耐储存、食品级、含有至少 3% MIC 的辣木浓缩物 (MC)。初步研究表明，MIC 等于或超过萝卜硫素（西兰花中一种著名的 ITC）的生物活性。 MC 和 MIC 均显着降低了体外模型中炎症标志物的表达和水平，例如 iNOS、IL-1ß 和 TNFα，以及高脂肪饮食小鼠肠道组织和粪便中的 TNFα 水平。拟议的工作是与罗格斯大学 Ilya Raskin 博士（植物药和炎症方面的领先专家）实验室以及在天然产物和 IBD 各个方面经验丰富的三名顾问密切合作进行的，将评估 MC 中提供的 MIC 的生物利用度和毒理学。我们将进一步在体外Caco-2细胞模型中研究MC和MIC的抗炎作用，以阐明MIC的作用机制，并研究MC在右旋糖酐硫酸钠（DSS）诱导的急慢性溃疡性结肠炎小鼠模型中的作用。最后，我们将调查和比较生长在不同气候和地理区域的各种辣木品种的 MIC 含量，并确定和优化商业规模的 MC 生产方法，例如伤口、残留物去除和干燥。