Zheng Qianqian, Luo Xin, Pan Daodong, Wang Yanli, Suo Shikun, Dang Yali, Gao Xinchang
College of Food Science and Engineering, Ningbo University, Ningbo, China.
Institute of Drug Discovery Technology, Ningbo University, Ningbo, China.
J Sci Food Agric. 2025 May;105(7):3942-3950. doi: 10.1002/jsfa.14138. Epub 2025 Jan 31.
Peptidomics combined with molecular docking is an effective alternative method for rapid screening of novel bioactive peptides in food. Buffalo milk as a potential source of dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides has been less studied. Peptidomics and molecular docking methods were employed to rapidly screen new DPP-IV inhibitory peptides from buffalo milk. The screened DPP-IV inhibitory peptides were further verified using an in vitro inhibition assay and a Caco-2 cell assay.
The DPP-IV inhibition rate of buffalo milk was increased from 73.40 ± 6.01% to 97.23 ± 3.18% in an in vitro digestion assay, suggesting that buffalo milk could be a promising source of DPP-IV inhibitory peptides. Subsequently, two novel peptides (GPFPIIV and FPQYL) with potential DPP-IV inhibitory activity were screened using peptidomics, molecular docking and an in vitro inhibitory assay. The IC values for GPFPIIV and FPQYL were 0.2998 ± 0.03 and 0.1407 ± 0.01 mg mL, respectively. During simulated gastrointestinal digestion in vitro, FPQYL had an excellent digestive stability of 92.13 ± 1.03%, whereas that of GPFPIIV was 59.52 ± 2.56%. In addition, GPFPIIV and FPQYL (1.00 mg mL) showed significant DPP-IV inhibitory effects in a Caco-2 cell assay, with the inhibition rate increasing to 32% and 36%, respectively.
In summary, two new DPP-IV inhibitory peptides were screened from buffalo milk through a combination of peptidomics and molecular docking, both of which exhibited significant DPP-IV inhibitory activities. The identified peptides, GPFPIIV and FPQYL, have promising applications in diabetes management. © 2025 Society of Chemical Industry.
肽组学与分子对接相结合是快速筛选食品中新型生物活性肽的有效替代方法。水牛奶作为二肽基肽酶-IV（DPP-IV）抑制肽的潜在来源，相关研究较少。采用肽组学和分子对接方法从水牛奶中快速筛选新的DPP-IV抑制肽。通过体外抑制试验和Caco-2细胞试验对筛选出的DPP-IV抑制肽进行进一步验证。
在体外消化试验中，水牛奶的DPP-IV抑制率从73.40±6.01%提高到97.23±3.18%，表明水牛奶可能是DPP-IV抑制肽的一个有前景的来源。随后，通过肽组学、分子对接和体外抑制试验筛选出两种具有潜在DPP-IV抑制活性的新型肽（GPFPIIV和FPQYL）。GPFPIIV和FPQYL的IC值分别为0.2998±0.03和0.1407±0.01mg/mL。在体外模拟胃肠道消化过程中，FPQYL具有92.13±1.03%的优异消化稳定性，而GPFPIIV为59.52±2.56%。此外，GPFPIIV和FPQYL（1.00mg/mL）在Caco-2细胞试验中显示出显著的DPP-IV抑制作用，抑制率分别提高到32%和36%。
综上所述，通过肽组学和分子对接相结合的方法从水牛奶中筛选出两种新的DPP-IV抑制肽，它们均表现出显著的DPP-IV抑制活性。鉴定出的肽GPFPIIV和FPQYL在糖尿病管理方面具有广阔的应用前景。©2025化学工业协会。
