Identification of anti-inflammatory compounds from chocolate for the treatment of

描述（由申请人提供）：这项1期SBIR申请的目标是鉴定和结构表征巧克力中可用于治疗牙龈炎和牙周炎相关组织炎症的化合物。先前的研究表明，可可豆壳和巧克力的水溶性提取物可以含有抗炎和/或抑制牙菌斑的活性。然而，这些提取物实际上是难吃的，这是口服制剂的一个重大限制。对巧克力制造过程中产生的潜在有用化合物的结构-功能关系的控制评价尚未进行。在本研究中，我们将对已知来源、发酵特征和特定热处理步骤的可可样品的提取物进行分析表征和制备层析分离，并筛选由核梭杆菌脂多糖诱导的哺乳动物细胞系中Nf-kB活化的抑制作用。具有Nf-kB拮抗活性的巧克力提取物的组分将通过质谱法进行初步表征，并进一步分离以确保所观察到的活性是由单一化学物质引起的。第一阶段的研究将导致第二阶段的项目，在那里确定的结构将进一步表征其作用机制，并评估它们作为一种新的、安全的、有效的、具有成本效益的牙龈炎和牙周炎干预措施纳入新型牙龈或漱口水中。

DESCRIPTION (provided by applicant): The goal of this Phase 1 SBIR application is to identify and structurally characterize compounds in chocolate that could be used to treat tissue inflammation associated with gingivitis and periodontitis. Previous studies have demonstrated that water soluble extracts of cocoa bean husks and chocolate can contain activity that is either anti-inflammatory and/or dental plaque inhibiting. However, these extracts are practically unpalatable, a significant limitation for an oral formulation. Controlled evaluation of the structure-function relationships of potentially useful compounds arising during the chocolate manufacturing process has not been performed. In this proposal, extracts of characterized cocoa samples with known origin, fermentation profiles and specific heat treatment steps will be subjected to analytical characterization and preparative chromatographic separation and screened for the inhibition of Nf-kB activation in a mammalian cell line induced by lipopolysaccharides derived from Fusobacterium nucleatum. Fractions of chocolate extracts exhibiting Nf-kB antagonistic activity will be subject to initial characterization by mass spectrometry, and further separated to ensure that single chemical species are responsible for the observed activity. This Phase 1 research will lead to a Phase 2 project, where identified structures will be further characterized with respect to their mechanism of action and evaluated for their incorporation into a novel gum or mouthwash as a novel, safe, efficacious and cost-effective intervention for gingivitis and periodontitis. PUBLIC HEALTH RELEVANCE: Periodontal and gingival disease affects the majority of adults, can lead to tooth loss and has been associated with increased risks of cardiovascular disease and preterm birth, two conditions with high morbidity and mortality. There is compelling scientific evidence that extracts of cocoa display anti-inflammatory and dental plaque inhibiting characteristics but these chemistries are unpalatable for oral formulations. We propose a comprehensive evaluation of potentially useful compounds, with better flavor characteristics, generated during the chocolate manufacturing process that will lead to a better understanding of the therapeutic potential for cocoa in oral health applications and the development of products to prevent and control gingivitis and periodontitis.