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

描述（由申请人提供）：慢性低度炎症与肥胖相关代谢疾病的发病机制存在因果关系，如胰岛素抵抗（IR）、2型糖尿病、心血管疾病和非酒精性脂肪肝。脂肪细胞中的脂肪过载触发循环单核细胞募集到富含脂质的脂肪组织中，其产生大量促炎介质。这扰乱了脂肪组织中的胰岛素信号传导，最终诱导全身性炎症和IR。因此，代谢和炎症组分在很大程度上促成了肥胖症中慢性低度炎症的发展。补充和替代医学（CAM）的天然产品，可以有效地打击慢性炎症与最小的不良副作用是非常需要的。钝顶螺旋藻（SP）是一种蓝绿色藻（BGA），已被证明可安全供人类食用。在过去的几年中，我们研究了BGA提取物的抗炎特性，更具体地说，SP有机提取物（SPE）使用体外和体内模型，并发现了大量的证据，证明它们在预防肥胖引起的炎症方面的潜力。然而，我们对可食用BGA的生物活性成分的认识存在重大差距，这阻碍了这些CAM天然产物的标准化和更广泛的利用。关于BGA的化学成分知之甚少。目前，标准化利用β-胡萝卜素、总类胡萝卜素和/或藻蓝蛋白含量用于质量保证。这些组分尚未显示出引起BGA的有效抗炎活性，因此不是用于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：SA 1，从SP提取物中分离和鉴定抗炎化合物; SA 2，鉴定SP提取物和纯化化合物抗炎作用的分子机制。负责BGA抗炎作用的生物活性代谢物的鉴定将有助于支持这些CAM产品的未来标准化，有关其作用机制的其他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.