Wang Yali, Wang Yue, Fang Baishan, Fu Yousi
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Department of Microbiology, Genetics, & Immunology, Michigan State University, East Lansing, MI 48824, USA.
Int J Mol Sci. 2025 May 10;26(10):4570. doi: 10.3390/ijms26104570.
Collagen peptides are recognized for their diverse bioactivities; however, efficiently screening potent peptides from hydrolysates remains challenging. This study employed an integrated strategy that combined in silico antioxidant activity prediction and molecular docking to myeloperoxidase (MPO) to screen active peptides derived from yak bone collagen hydrolysates. Focusing on low molecular weight peptides, containing motifs such as GVM, GLP, GPM, and GPQ, we identified nine antioxidant peptides (KC1-KC9). Their activities were validated through in vitro free radical scavenging assays, with peptide KC7 demonstrating superior performance. Furthermore, peptide KC7 promoted proliferation, differentiation, and mineralization in MC3T3-E1 cells by upregulating osteogenic markers such as Runx2 and osteocalcin, modulating the Wnt/β-catenin and PI3K/Akt pathways, and reducing the Bax/Bcl-2 ratio. These results highlight KC7's dual capacity to mitigate oxidative stress and potentially reduce apoptotic susceptibility, thereby stimulating osteogenesis. This positions peptide KC7 as a promising candidate for bone regeneration and oxidative stress-related disorders. Moreover, this study underscores the effectiveness of integrating computational and experimental approaches for the discovery of multifunctional natural peptides.
胶原蛋白肽因其多样的生物活性而受到认可；然而，从水解产物中高效筛选出有效的肽仍然具有挑战性。本研究采用了一种综合策略，将计算机模拟抗氧化活性预测与对髓过氧化物酶（MPO）的分子对接相结合，以筛选源自牦牛骨胶原蛋白水解产物的活性肽。聚焦于含有GVM、GLP、GPM和GPQ等基序的低分子量肽，我们鉴定出了9种抗氧化肽（KC1 - KC9）。通过体外自由基清除试验验证了它们的活性，其中肽KC7表现出卓越的性能。此外，肽KC7通过上调成骨标志物如Runx2和骨钙素、调节Wnt/β - 连环蛋白和PI3K/Akt信号通路以及降低Bax/Bcl - 2比率，促进了MC3T3 - E1细胞的增殖、分化和矿化。这些结果突出了KC7减轻氧化应激以及潜在降低凋亡易感性从而刺激成骨的双重能力。这使得肽KC7成为骨再生和氧化应激相关疾病的一个有前景的候选物。此外，本研究强调了整合计算和实验方法来发现多功能天然肽的有效性。
