Identification of bioactive peptides from digestion of collagen hydrolysates

Genacol Canada Corporation Inc. 生产一种牛源水解胶原蛋白补充剂（Genacol® 原始配方），该补充剂在两项独立的临床试验中显示出对减轻骨关节炎 (OA) 受试者关节疼痛的功效。消化后，水解胶原蛋白会产生氨基酸和肽，从而使补充剂具有促进健康的特性。然而，目前还没有关于 Genacol 补充剂消化产生的肽和氨基酸谱的信息。关于到达关节的胶原蛋白肽及其作用机制也缺乏关键信息。在本提案中，将使用动态模拟肠道消化模型研究消化酶介导的 Genacol 胶原蛋白产品水解产生的肽和氨基酸的概况。为了鉴定生物可利用的肽，将从动态模拟人体胃肠道模型中获得的 CH 消化物的肽部分暴露于人体肠道和肝细胞共培养系统中，该系统模拟将到达血液循环的肽。将研究从共培养中获得的肽在人 OA 关节软骨组织中的抗炎作用。此外，还将研究模拟消化研究中产生的肽的抗炎作用，涉及人类肠道细胞、免疫细胞和肠道树突状细胞的共培养，这些细胞参与控制也可能损害关节健康的促炎因子。这种方法将有助于确定有助于 Genacol 胶原蛋白补充剂健康促进特性的生物活性成分，并将有助于开发更浓缩、更有效的水解胶原蛋白产品。根据在 OA 软骨组织外植体中显示出生物活性的生物可利用肽谱，Genacol 将生产富含这些肽的 CH 制剂，并在上述测试系统中测试其生物利用度和生物活性。

Genacol Canada Corporation Inc. manufactures a bovine-sourced hydrolyzed collagen supplement (Genacol®Original Formula), which has shown efficacy in two separate clinical trials for reducing joint pain in subjects with osteoarthritis (OA). Following digestion, hydrolyzed collagen yields amino acids and peptides that can lead to the health promoting properties of the supplement. There is presently no information, however, regarding the peptide and amino acid profiles generated from the digestion of the Genacol supplement. Key information is also lacking regarding the collagen peptides reaching the joint and their mechanisms of action. In the present proposal, the profiles of the peptides and amino acids generated from digestive enzyme-mediated hydrolysis of the Genacol collagen product will be investigated using the dynamic simulated gut digestion model. To identify bioavailable peptides, the peptide fractions of the CH digests obtained from a dynamic simulated human GI model will be exposed to a human intestinal and liver cell co-culture system that simulates peptides that would reach the blood circulation. The peptides obtained from the co-culture will be studied for their anti-inflammatory effects in human OA articular cartilage tissue. Also, peptides generated during the simulated digestion studies will be investigated for their anti-inflammatory effects involving a co-culture of human intestinal cells, immune cells and intestinal dendritic cells involved in controlling pro-inflammatory factors that could also compromise joint health. This approach will help to ascertain the bioactive components contributing towards the health promoting properties of the Genacol collagen supplement and will aid in the development of more concentrated and potent hydrolyzed collagen products. Based on the profiles of bioavailable peptides shown to be bioactive in the OA cartilage tissue explants, Genacol will manufacture CH formulations enriched in those peptides that will be tested for their bioavailability and bioactivity in the above testing systems.