Identification of bioactive peptides from digestion of collagen hydrolysates

Genacol加拿大公司生产一种牛源水解胶原蛋白补充剂（Genacol®Original Formula），该补充剂在两项单独的临床试验中显示出减轻骨关节炎（OA）受试者关节疼痛的功效。消化后，水解胶原蛋白产生氨基酸和肽，可以导致补充剂的健康促进特性。然而，目前没有关于Genacol补充剂消化产生的肽和氨基酸谱的信息。还缺乏关于到达关节的胶原肽及其作用机制的关键信息。在本提案中，将使用动态模拟肠道消化模型研究Genacol胶原蛋白产品的消化酶介导的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GI模型获得的CH肽的肽级分暴露于模拟将到达血液循环的肽的人肠和肝细胞共培养系统。将研究从共培养物获得的肽在人OA关节软骨组织中的抗炎作用。此外，将研究模拟消化研究期间产生的肽的抗炎作用，涉及人肠细胞、免疫细胞和肠树突状细胞的共培养，这些细胞参与控制促炎因子，这些促炎因子也可能损害关节健康。这种方法将有助于确定有助于Genacol胶原蛋白补充剂的健康促进特性的生物活性成分，并将有助于开发更浓缩和更有效的水解胶原蛋白产品。根据OA软骨组织外植体中显示具有生物活性的生物可利用肽的特征，Genacol将生产富含这些肽的CH制剂，这些肽将在上述试验系统中进行生物利用度和生物活性试验。

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.