Stable, antiinflammatory isothiocyanates from moringa may prevent and treat IBD

 描述(由申请人提供)：这个第一阶段的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)的创新和专有植物产品。我们的目的是为抗炎异硫氰酸酯(ITCs)天然产生于辣木可食叶子的假说提供实验支持。机械伤害后的辣木提供稳定、高效和实用的替代品，取代十字花科(十字花科)植物(如花椰菜)产生的不稳定和挥发性的ITCs。辣木叶在整个南亚和非洲历史上被用作一种营养食品和传统药物。它们含有高水平的营养、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硫代葡萄糖苷，可以在受伤的叶片中转化为具有生物活性的稳定的辣木异硫氰酸酯(MICs)。我们开发了一种新颖、简单和专有的水提/生物转化方法，可以有效地将辣木硫代葡萄糖酸盐转化为MICs，从而获得口感好、货架稳定、食品级的辣木浓缩物(MC)，其MICs含量至少为3%。初步研究表明，最低抑菌浓度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著名ITC。MC和MICS均能显著降低高脂饮食小鼠肠道组织和粪便中炎性标志物诱导型一氧化氮合酶、白介素1、肿瘤坏死因子的表达和水平，降低肠道组织和粪便中肿瘤坏死因子的水平。这项拟议的工作是与罗格斯大学的伊利亚·拉斯金博士(植物学和炎症方面的领先专家)的实验室和三名在天然产品和IBD的各个方面都有经验的顾问密切合作进行的，将评估MC提供的MIC的生物利用度和毒理学。我们将进一步研究MC和MICS在体外Caco-2细胞模型中的抗炎作用，目的是阐明MICS的作用机制，并研究MC在葡聚糖硫酸钠(DSS)诱导的小鼠急、慢性溃疡性结肠炎模型中的作用。最后，我们将调查和比较生长在不同气候和地理区域的不同辣木品种的最低抑菌浓度，并确定和优化商业规模的MC制造方法，如损伤、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.