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

描述（由申请人提供）：本SBIR申请的第1阶段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。先前的研究已经证明，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不可口的，这是口服制剂的显著限制。尚未对巧克力生产过程中产生的潜在有用化合物的结构-功能关系进行受控评价。在本提案中，将对具有已知来源、发酵概况和特定热处理步骤的表征可可样品的提取物进行分析表征和制备色谱分离，并筛选对哺乳动物细胞系中由源自具核梭杆菌的脂多糖诱导的Nf-kB活化的抑制。表现出Nf-kB拮抗活性的巧克力提取物的级分将通过质谱进行初始表征，并进一步分离以确保单一化学物质负责观察到的活性。这项第一阶段的研究将导致第二阶段的项目，其中确定的结构将进一步表征其作用机制，并评估其作为牙龈炎和牙周炎的新型，安全，有效和具有成本效益的干预措施纳入新型牙龈或漱口水。 公共卫生相关性：牙周病和牙龈疾病影响大多数成年人，可导致牙齿脱落，并与心血管疾病和早产的风险增加有关，这两种疾病具有高发病率和死亡率。有令人信服的科学证据表明，可可提取物显示出抗炎和抑制牙菌斑的特性，但这些化学物质对于口服制剂来说是不可口的。我们建议对巧克力制造过程中产生的具有更好风味特征的潜在有用化合物进行全面评估，这将有助于更好地了解可可在口腔健康应用中的治疗潜力，以及开发预防和控制牙龈炎和牙周炎的产品。

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.