Metabolites from Edible Blue-Green Algae for Obesity-Induced Inflammation

描述(申请人提供)：慢性低度炎症与肥胖相关代谢性疾病的发病机制有关，如胰岛素抵抗(IR)、2型糖尿病、心血管疾病和非酒精性脂肪性肝病。脂肪细胞中的脂肪过载会触发循环中的单核细胞重新聚集到富含脂肪的脂肪组织中，从而产生大量的促炎介质。这扰乱了脂肪组织中的胰岛素信号，最终导致全身炎症和IR。因此，代谢和炎症成分在很大程度上促进了肥胖症慢性低度炎症的发展。补充和替代医学(CAM)天然产品可以有效地抗击慢性炎症，并将副作用降至最低，这是非常需要的。钝顶螺旋藻是一种蓝绿色藻类，已被证明可供人类安全食用。在过去的几年里，我们使用体外和体内模型研究了BGA提取物，更具体地说是SP有机提取物(SPE)的抗炎特性，并发现了大量证据表明它们在预防肥胖引起的炎症方面具有潜力。然而，我们对食用BGA的生物活性成分的认识存在重大空白，这阻碍了这些CAM天然产品的标准化和更广泛的应用。人们对BGA的化学成分知之甚少。目前，标准化使用胡萝卜素、总胡萝卜素和/或藻蓝蛋白含量来保证质量。这些成分还没有被证明能引起BGA的有效抗炎活性，因此不是基于生物活性的化学标准化的适当标记化合物。因此，提出了以下具体目标：SA1，从SP提取物中分离和鉴定抗炎化合物；以及SA2，鉴定SP提取物和纯化化合物的抗炎作用的分子机制。确定对BGA的抗炎作用负责的生物活性代谢物将有助于支持这些CAM产品的未来标准化，有关其作用机制的更多信息将允许进一步的临床前和临床开发。

DESCRIPTION (provided by applicant): Chronic low-grade inflammation is causally linked to the pathogenesis of obesity-associated metabolic diseases, such as insulin resistance (IR), type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Fat overload in the adipocyte triggers circulating monocyte recruitment into lipid-laden adipose tissue, which produces a large quantity of pro-inflammatory mediators. This perturbs insulin signaling in adipose tissue, eventually inducing systemic inflammation and IR. As such, both metabolic and inflammatory components largely contribute to the development of chronic low-grade inflammation in obesity. Complementary and alternative medicine (CAM) natural products that can effectively combat chronic inflammation with minimal adverse side-effects are much needed. Spirulina platensis (SP) is a blue-green alga (BGA) that has proven to be safe for human consumption. During the past several years, we have investigated anti-inflammatory properties of BGA extracts, and more specifically a SP organic extract (SPE) using both in vitro and in vivo models and have found substantial evidence for their potential in the prevention of obesity-induced inflammation. However, major gaps exist in our knowledge regarding the bioactive components from edible BGA, which hinders the standardization and broader utilization of these CAM natural products. Very little is known about the chemical composition of BGA. Currently, standardization utilizes -carotene, total carotenoids, and/or phycocyanin content for quality assurance. These components have not been shown to cause the potent anti-inflammatory activity of BGA and thus are not appropriate marker compounds for chemical standardization based on biological activity. The following specific aims are thus proposed: SA1, isolation and identification of anti-inflammatory compounds from SP extracts; and SA2, identification of molecular mechanisms responsible for anti-inflammatory effects of SP extracts and purified compounds. The identification of bioactive metabolites responsible for the anti-inflammatory effects of BGA will help to support future standardization of these CAM products and additional information regarding their mechanism of action will allow for further preclinical and clinical development.