Skip to main content
Log in

Identification of dipeptidyl peptidase-IV inhibitory peptides from yak bone collagen by in silico and in vitro analysis

  • Original Paper
  • Published:
European Food Research and Technology Aims and scope Submit manuscript

Abstract

The fast development of bioinformatics and various established databases of bioactive peptides provide time-saving and efficient method for identifying bioactive peptides from various proteins. The yak bone collagen is rich in nutrition and have various potential bioactivities, but the study on yak bone collagen as a precursor of antidiabetic peptide has not been reported. In this study, yak bone collagen was first evaluated as a precursor to generate dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides by in silico analysis. After multi-cycles of screening, three peptides (GHR, GIR and MGPR) were screened out and synthesized to evaluate their inhibitory activities in vitro. Among the three peptides, MGPR had the best inhibitory effect on DPP-IV with IC50 of 0.490 ± 0.012 mM. Further cell test verified that MGPR could ameliorate glucosamine-induced glucose uptake reduction in HepG2 cells. These results suggested that yak bone collagen could be applied as a good precursor for antidiabetic peptides. This study would further broaden the application of yak bone collagen in the fields of the food and pharmaceuticals industry.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Yang Y, Shi CY, Xie J, Dai JH, He SL, Tian Y (2020) Identification of potential dipeptidyl peptidase (DPP)-IV inhibitors among Moringa oleifera phytochemicals by virtual screening, molecular docking analysis, ADME/T-based prediction, and in vitro analyses. Molecules 25:189

    Article  CAS  Google Scholar 

  2. Guo Z, Yi D, Hu B, Shi Y, Xin Y, Gu Z, Liu H, Zhang L (2021) The alteration of gut microbiota by bioactive peptides: a review. Syst Microbiol Biomanufacturing 1:363–377

    Article  CAS  Google Scholar 

  3. Langyan S, Khan FN, Yadava P, Alhazmi A, Mahmoud SF, Saleh DI, Zuan ATK, Kumar A (2021) In silico proteolysis and analysis of bioactive peptides from sequences of fatty acid desaturase 3 (FAD3) of flaxseed protein. Saudi J Biol Sci 28:5480–5489

    Article  CAS  Google Scholar 

  4. Qiu Q, Zhang G, Ma T, Qian W, Wang J, Ye Z, Cao C, Hu Q, Kim J, Larkin DM, Auvil L, Capitanu B, Ma J, Lewin HA, Qian X, Lang Y, Zhou R, Wang L, Wang K, Xia J, Liao S, Pan S, Lu X, Hou H, Wang Y, Zang X, Yin Y, Ma H, Zhang J, Wang Z, Zhang Y, Zhang D, Yonezawa T, Hasegawa M, Zhong Y, Liu W, Zhang Y, Huang Z, Zhang S, Long R, Yang H, Wang J, Lenstra JA, Cooper DN, Wu Y, Wang J, Shi P, Wang J, Liu J (2012) The yak genome and adaptation to life at high altitude. Nat Genet 44:946–949

    Article  CAS  Google Scholar 

  5. Gao S, Hong H, Zhang C, Wang K, Zhang B, Han Q-a, Liu H, Luo Y (2019) Immunomodulatory effects of collagen hydrolysates from yak (Bos grunniens) bone on cyclophosphamide-induced immunosuppression in BALB/c mice. J Funct Foods 60:103420

    Article  CAS  Google Scholar 

  6. Sun X, Wang K, Gao S, Hong H, Zhang L, Liu H, Feng L, Luo Y (2021) Purification and characterization of antioxidant peptides from yak (Bos grunniens) bone hydrolysates and evaluation of cellular antioxidant activity. J Food Sci Technol 58:3106–3119

    Article  CAS  Google Scholar 

  7. Guo Z, Liu C, Hu B, Zhu L, Yang Y, Liu F, Gu Z, Xin Y, Zhang L (2021) Simulated gastrointestinal digestion of yak bone collagen hydrolysates and insights into its effects on gut microbiota composition in mice. Food Biosci 44:101463

    Article  CAS  Google Scholar 

  8. Guo H, Richel A, Hao Y, Fan X, Everaert N, Yang X, Ren G (2020) Novel dipeptidyl peptidase-IV and angiotensin-I-converting enzyme inhibitory peptides released from quinoa protein by in silico proteolysis. Food Sci Nutr 8:1415–1422

    Article  CAS  Google Scholar 

  9. Liu R, Cheng J, Wu H (2019) Discovery of food-derived dipeptidyl peptidase iv inhibitory peptides: a review. Int J Mol Sci 20:463

    Article  CAS  Google Scholar 

  10. Lin K, Zhang LW, Han X, Xin L, Meng ZX, Gong PM, Cheng DY (2018) Yak milk casein as potential precursor of angiotensin I-converting enzyme inhibitory peptides based on in silico proteolysis. Food Chem 254:340–347

    Article  CAS  Google Scholar 

  11. Ma DL, Chan DS, Leung CH (2013) Drug repositioning by structure-based virtual screening. Chem Soc Rev 42:2130–2141

    Article  CAS  Google Scholar 

  12. Udenigwe CC (2014) Bioinformatics approaches, prospects and challenges of food bioactive peptide research. Trends Food Sci Technol 36:137–143

    Article  CAS  Google Scholar 

  13. Bjelke JR, Christensen J, Nielsen PF, Branner S, Kanstrup AB, Wagtmann N, Rasmussen HB (2006) Dipeptidyl peptidases 8 and 9: specificity and molecular characterization compared with dipeptidyl peptidase IV. Biochem J 396:391–399

    Article  CAS  Google Scholar 

  14. Tulipano G, Sibilia V, Caroli AM, Cocchi D (2011) Whey proteins as source of dipeptidyl dipeptidase IV (dipeptidyl peptidase-4) inhibitors. Peptides 32:835–838

    Article  CAS  Google Scholar 

  15. Lee CY (2016) Glucagon-like peptide-1 formulation–the present and future development in diabetes treatment. Basic Clin Pharm Toxicol 118:173–180

    Article  CAS  Google Scholar 

  16. Chen L, Teng H, Cao H (2019) Chlorogenic acid and caffeic acid from Sonchus oleraceus Linn synergistically attenuate insulin resistance and modulate glucose uptake in HepG2 cells. Food Chem Toxicol 127:182–187

    Article  CAS  Google Scholar 

  17. Xu W, Li J, Qi W, Peng Y, Zhang Y (2021) Hypoglycemic effect of vitexin in C57BL/6J mice and HepG2 models. J Food Qual 2021:1–7

    Article  Google Scholar 

  18. Minkiewicz P, Iwaniak A, Darewicz M (2019) BIOPEP-UWM database of bioactive peptides: current opportunities. Int J Mol Sci 20:5978

    Article  CAS  Google Scholar 

  19. Mooney C, Haslam NJ, Pollastri G, Shields DC (2012) Towards the improved discovery and design of functional peptides: common features of diverse classes permit generalized prediction of bioactivity. PLoS ONE 7:e45012

    Article  CAS  Google Scholar 

  20. Duvaud S, Gabella C, Lisacek F, Stockinger H, Ioannidis V, Durinx C (2021) Expasy, the swiss bioinformatics resource portal, as designed by its users. Nucleic Acids Res 49:W216

    Article  CAS  Google Scholar 

  21. Tu M, Qiao X, Wang C, Liu H, Cheng S, Xu Z, Du M (2021) In vitro and in silico analysis of dual-function peptides derived from casein hydrolysate. Food Sci Human Wellness 10:32–37

    Article  CAS  Google Scholar 

  22. Lafarga T, O’Connor P, Hayes M (2015) In silico methods to identify meat-derived prolyl endopeptidase inhibitors. Food Chem 175:337–343

    Article  CAS  Google Scholar 

  23. Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, Yin M, Zeng X, Wu C, Lu A, Chen X, Hou T, Cao D (2021) ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res 49:(W1)

    Article  Google Scholar 

  24. Zhu D, Wang Y, Du Q, Liu Z, Liu X (2015) Cichoric acid reverses insulin resistance and suppresses inflammatory responses in the glucosamine-induced HepG2 cells. J Agric Food Chem 63:10903–10913

    Article  CAS  Google Scholar 

  25. Hong H, Fan H, Chalamaiah M, Wu J (2019) Preparation of low-molecular-weight, collagen hydrolysates (peptides): current progress, challenges, and future perspectives. Food Chem 301:125222

    Article  CAS  Google Scholar 

  26. Chen J, Yu X, Chen Q, Wu Q, He Q (2021) Screening and mechanisms of novel angiotensin-I-converting enzyme inhibitory peptides from rabbit meat proteins: a combined in silico and in vitro study. Food Chem 370:131070

    Article  Google Scholar 

  27. Sienkiewicz-Szłapka E, Jarmołowska B, Krawczuk S, Kostyra E, Kostyra H, Bielikowicz K (2009) Transport of bovine milk-derived opioid peptides across a Caco-2 monolayer. Int Dairy J 19:252–257

    Article  Google Scholar 

  28. Xu Q, Hong H, Wu J, Yan X (2019) Bioavailability of bioactive peptides derived from food proteins across the intestinal epithelial membrane: a review. Trends Food Sci Technol 86:399–411

    Article  CAS  Google Scholar 

  29. Zhao W, Zhang D, Yu Z, Ding L, Liu J (2020) Novel membrane peptidase inhibitory peptides with activity against angiotensin converting enzyme and dipeptidyl peptidase IV identified from hen eggs. J Funct Foods 64:103679

    Article  Google Scholar 

  30. Kim BR, Kim HY, Choi I, Kim JB, Jin CH, Han AR (2018) DPP-IV inhibitory potentials of flavonol glycosides isolated from the seeds of lens culinaris: in vitro and molecular docking analyses. Molecules 23:1998

    Article  Google Scholar 

  31. Zhu Q, Chen X, Wu J, Zhou Y, Qian Y, Fang M, Xie J, Wei D (2017) Dipeptidyl peptidase IV inhibitory peptides from Chlorella vulgaris: in silico gastrointestinal hydrolysis and molecular mechanism. Eur Food Res Technol 243:1739–1748

    Article  CAS  Google Scholar 

  32. Glowacki ED, Irimia-Vladu M, Bauer S, Sariciftci NS (2013) Hydrogen-bonds in molecular solids—from biological systems to organic electronics. J Mater Chem B 1:3742–3753

    Article  CAS  Google Scholar 

  33. Mudgil P, Kamal H, Priya Kilari B, Mohd Salim MAS, Gan CY, Maqsood S (2021) Simulated gastrointestinal digestion of camel and bovine casein hydrolysates: Identification and characterization of novel anti-diabetic bioactive peptides. Food Chem 353:129374

    Article  CAS  Google Scholar 

  34. Nongonierma AB, FitzGerald RJ (2019) Features of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from dietary proteins. J Food Biochem 43:e12451

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by Postdoctoral Science Foundation of Jiangsu Province (2021K269B), the National Key Research & Developmental Program of China (2021YFC2100300), China Agriculture Research System of Finance and Agriculture Ministry (No. CARS-11-HNSHY), and Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences (No. 1630052021012, 1630052020023, 1630052020024).

Author information

Authors and Affiliations

Authors

Contributions

CL, methodology, investigation, data curation, writing—original draft, project administration; YY, BH, LZ, ML, methodology, investigation, data curation; ZG, YX, ZG, HS, YG, LZ, conceptualization, writing—review and editing, supervision. All authors contributed to discussion and review of the manuscript.

Corresponding authors

Correspondence to Zitao Guo or Liang Zhang.

Ethics declarations

Conflict of interest

All authors have declared that there is no conflict of interest.

Compliance with ethics requirements

This article does not contain any studies with human or animal subjects.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 336 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, C., Guo, Z., Yang, Y. et al. Identification of dipeptidyl peptidase-IV inhibitory peptides from yak bone collagen by in silico and in vitro analysis. Eur Food Res Technol 248, 3059–3069 (2022). https://doi.org/10.1007/s00217-022-04111-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00217-022-04111-x

Keywords

Navigation