Stable, antiinflammatory isothiocyanates from moringa may prevent and treat IBD

 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慢性炎症性疾病（如炎症性肠病（IBD））的创新和专有植物产品。我们的目的是提供实验支持的假设，抗炎异硫氰酸酯（ITCs）天然产生的食用辣木叶。（辣木属）植物在机械损伤后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，所述替代品由十字花科（十字花科）植物如花椰菜产生。辣木叶在历史上被用作南亚和非洲的营养食品和传统药物。它们含有高水平的营养素、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修饰的芳香族芥子油苷，其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、简单和专有的水提取/生物转化方法，该方法有效地将辣木芥子油苷转化为MIC，从而产生口感好、货架稳定、食品级的辣木浓缩物（MC），其中至少含有3%的MIC。初步研究表明，MIC等于或超过萝卜硫素的生物活性，萝卜硫素是一种来自西兰花的众所周知的ITC。MC和MIC均能显著降低体外模型中炎症标志物如iNOS、IL-1 β和TNF α的表达和水平，以及高脂饮食小鼠肠组织和粪便中TNF α的水平。拟议的工作与罗格斯大学的Ilya Raskin博士（植物药和炎症领域的领先专家）实验室和三位在天然产物和IBD的各个方面经验丰富的顾问密切合作，将评估MC中MIC的生物利用度和毒理学。我们将进一步研究MC和MIC在体外Caco-2细胞模型中的抗炎作用，目的是阐明MIC的作用机制，并研究MC在葡聚糖硫酸钠（DSS）诱导的急性和慢性溃疡性结肠炎小鼠模型中的作用。最后，我们将调查和比较在不同气候和地理区域生长的各种辣木品种的MIC含量，并定义和优化商业规模的MC制造方法，如创伤，残留物去除和干燥。

 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.