Identification of bioactive peptides from digestion of collagen hydrolysates

Genacol Canada Corporation Inc.生产一种牛来源的水解胶原蛋白补充剂(Genacol®原始配方)，该补充剂已在两个单独的临床试验中显示出降低骨关节炎(OA)患者关节疼痛的效果。消化后，水解胶原蛋白产生氨基酸和多肽，可以导致补充剂的健康促进特性。然而，目前还没有关于Genacol补充剂消化产生的多肽和氨基酸图谱的信息。关于到达关节的胶原肽及其作用机制，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来研究Genacol胶原蛋白产品的消化酶介导的水解所产生的多肽和氨基酸的分布。为了确定生物可利用的多肽，从动态模拟人类GI模型中获得的CH消化的多肽部分将暴露在人体肠道和肝脏细胞共培养系统中，该系统模拟将到达血液循环的多肽。从共培养中获得的多肽将用于研究它们在人骨关节炎关节软骨组织中的抗炎作用。此外，在模拟消化研究中产生的多肽将被研究其抗炎作用，涉及人类肠道细胞、免疫细胞和肠道树突状细胞的共同培养，这些细胞参与控制促炎因素，这些因素也可能危及关节健康。这种方法将有助于确定Genacol胶原蛋白补充剂促进健康的生物活性成分，并有助于开发更集中和更有效的水解胶原蛋白产品。根据在骨性关节炎软骨组织外植体中被证明具有生物活性的生物可用多肽的概况，Genacol将生产富含这些多肽的CH配方，这些多肽将在上述测试系统中进行生物利用度和生物活性测试。

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.