Oral collagen-based supplement as a bioactive component in functional foods

Abstract

Collagen, an abundant extracellular matrix protein in food-producing animals, is widely integrated into food systems for its unique physicochemical properties. Oral collagen-based supplements have received increasing attention for their potential to enhance overall well-being. This review aims to provide valuable insights into the application of oral collagen supplements in food systems, promoting their broader use in food processing, preservation, and the development of functional foods. Specifically, the applications of oral collagen-based supplements in functional foods, focusing on their biological activities, health benefits, and functional properties are summarized. Importantly, their molecular mechanisms of biological activities are critically discussed, including antioxidant, angiotensin-converting enzyme inhibitory, and dipeptidyl peptidase IV inhibitory activities. The health benefits of oral collagen-based supplements, particularly in improving skin, immune, and gastrointestinal health are also explored. Additionally, various functional properties of collagen-based supplements are evaluated, including their stability, bioavailability, taste masking, and sensory attributes.

Graphical abstract

Keywords

Oral collagen-based supplements / Functional foods / Molecular mechanisms / Health benefits / Applications

References

[1] GranatoD, BarbaFJ, Bursać KovačevićD, LorenzoJM, CruzAG, PutnikP. Functional foods: product development, technological trends, efficacy testing, and safety. Annu Rev Food Sci Technol, 2020, 11193-118.

[2] EssaMM, BishirM, BhatA, ChidambaramSB, Al-BalushiB, HamdanH, et al. . Functional foods and their impact on health. J Food Sci Technol, 2023, 60: 820-834.

[3] GreenM, AroraK, PrakashS. Microbial Medicine: prebiotic and probiotic functional foods to target obesity and metabolic syndrome. Int J Mol Sci, 2020, 2182890.

[4] FinneganD, TocmoR, LoscherC. Targeted application of functional foods as immune fitness boosters in the defense against viral infection. Nutrients, 2023, 15153371.

[5] KebouchiM, HafeezZ, Le RouxY, Dary-MourotA, GenayM. Importance of digestive mucus and mucins for designing new functional food ingredients. Food Res Int, 2020, 131: 108906.

[6] AsgaryS, RastqarA, KeshvariM. Functional food and cardiovascular disease prevention and treatment: a review. J Am Coll Nutr, 2018, 375429-455.

[7] MurataH, ZhangQ, ItoT, KawakamiR, SakamotoS, ToriiS, et al. . The combined effect of rowing exercise and the intake of functional foods containing inulin on muscle mass and bone mineral density in older Japanese women. Geriatr Gerontol Int, 2023, 2311779-787.

[8] VallianouN, StratigouT, ChristodoulatosGS, TsigalouC, DalamagaM. Probiotics, prebiotics, synbiotics, postbiotics, and obesity: current evidence, controversies, and perspectives. Curr Obes Rep, 2020, 9: 179-192.

[9] SerafiniM, PelusoI. Functional foods for health: the interrelated antioxidant and anti-inflammatory role of fruits, vegetables, herbs, spices and cocoa in humans. Curr Pharm Des, 2016, 22446701-6715.

[10] PeterleL, SanfilippoS, BorgiaF, Li PomiF, VadalàR, CostaR, et al. . The role of nutraceuticals and functional foods in skin cancer: mechanisms and therapeutic potential. Foods, 2023, 12132629.

[11] AndriamanohiarisoamananaFJ, FarghaliM, MohamedIMA, YoshidaG, ShiotaK, IharaI. Impact of tannery wastes on anaerobic co-digestion: enhancing biogas production and process efficiency. Collagen Leather, 2024, 6: 19.

[12] MaughanJ, GouveiaPJ, GonzalezJG, LeahyLM, WoodsI, O’ConnorC, et al. . Collagen/pristine graphene as an electroconductive interface material for neuronal medical device applications. Appl Mater Today, 2022, 29: 101629.

[13] SionkowskaA, AdamiakK, MusiałK, GadomskaM. Collagen based materials in cosmetic applications: a review. Mater, 2020, 13194217.

[14] FarooqS, AhmadMI, ZhengS, AliU, LiY, ShixiuC, et al. . A review on marine collagen: sources, extraction methods, colloids properties, and food applications. Collagen Leather, 2024, 6: 11.

[15] PuSY, HuangYL, PuCM, KangYN, HoangKD, ChenKH, et al. . Effects of oral collagen for skin anti-aging: a systematic review and meta-analysis. Nutrients, 2023, 1592080.

[16] ZhengL, TseomashkoN, VoronovaA, Vasil’kovA, HuX, WangX. Recent advances of collagen composite biomaterials for biomedical engineering: antibacterial functionalization and 3D-printed architecturalization. Collagen Leather., 2024, 6122.

[17] ChenL, LvY, XuF, ZhongF. The effect of oral supplements containing collagen peptides rich in X-Hyp or X-Hyp-Gly compared with normal collagen hydrolysates on skin elasticity and collagen holes: a randomised double-blind clinical study. Food Funct, 2023, 142310628-10638.

[18] MilaniM, ColomboF. Efficacy and tolerability of an oral supplement containing amino acids, iron, selenium, and marine hydrolyzed collagen in subjects with hair loss (androgenetic alopecia, AGA or FAGA or telogen effluvium). A prospective, randomized, 3-month, controlled, assessor-blinded study. Skin Res Technol, 2023, 296e13381.

[19] HexselD, ZagueV, SchunckM, SiegaC, CamozzatoFO, OesserS. Oral supplementation with specific bioactive collagen peptides improves nail growth and reduces symptoms of brittle nails. J Cosmet Dermatol, 2017, 164520-526.

[20] CzajkaA, KaniaEM, GenoveseL, CorboA, MeroneG, LuciC, et al. . Daily oral supplementation with collagen peptides combined with vitamins other bioactive compounds improves skin elasticity and has a beneficial effect on joint and general wellbeing. Nutr Res, 2018, 57: 97-108.

[21] JiangS, DongW, ZhangZ, XuJ, LiH, ZhangJ, et al. . A new iron supplement: the chelate of pig skin collagen peptide and Fe²⁺ can treat iron-deficiency anemia by modulating intestinal flora. Front Nutr, 2022, 9: 1055725.

[22] GajbhiyeS, WairkarS. Collagen fabricated delivery systems for wound healing: a new roadmap. Biomater Adv, 2022, 142: 213152.

[23] PierceJA, HocottJB. Studies on the collagen and elastin content of the human lung. J Clin Invest, 1960, 3918-14.

[24] AhmedM, VermaAK, PatelR. Collagen extraction and recent biological activities of collagen peptides derived from sea-food waste: a review. Sustain Chem Pharm, 2020, 18: 100315.

[25] YangB, LiuH, JiangL, ZengY, HanY, ShaC, et al. . 3D bioprinting of collagen-based materials for oral medicine. Collagen Leather, 2023, 5: 23.

[26] PeiY, JordanKE, XiangN, ParkerRN, MuX, ZhangL, et al. . Liquid-exfoliated mesostructured collagen from the bovine achilles tendon as building blocks of collagen membranes. ACS Appl Mater Interfaces, 2021, 1323186-3198.

[27] DebeerS, Le LuduecJB, KaiserlianD, LaurentP, NicolasJF, DuboisB, et al. . Comparative histology and immunohistochemistry of porcine versus human skin. Eur J Dermatol, 2013, 234456-466.

[28] ChiarelliPG, SuhJH, PeggRB, ChenJ, MisSK. The emergence of jellyfish collagen: L comprehensive review on research progress, industrial applications, and future opportunities. Trends Food Sci Technol, 2023, 144: 104206.

[29] CoppolaD, OlivieroM, VitaleGA, LauritanoC, D’AmbraI, IannaceS, et al. . Marine collagen from alternative and sustainable sources: extraction, processing and applications. Mar Drugs, 2020, 184214.

[30] GuoX, MaY, WangH, YinH, ShiX, ChenY, et al. . Status and developmental trends in recombinant collagen preparation technology. Regen Biomater, 2023, 11: rbad106.

[31] GovenderT, NaickerT. Insulin as a catalyst to recombinant DNA technology. Nat Catal, 2023, 66454-455.

[32] ValentaR, NiederbergerV. Recombinant allergens for immunotherapy. J Allergy Clin Immunol, 2007, 1194826-830.

[33] FushimiH, HiratsukaT, OkamuraA, OnoY, OguraI, NishimuraI. Recombinant collagen polypeptide as a versatile bone graft biomaterial. Commun Mater, 2020, 1187.

[34] MengjieS, DaniilA, DmitriiF, TeemuV, MarkusBL, ArankoAS. Phase separation drives the folding of recombinant collagen. Int J Biol Macromol, 2024, 282: 137170.

[35] ZhangX, XuS, ShenL, LiG. Factors affecting thermal stability of collagen from the aspects of extraction, processing and modification. J Leather Sci Eng, 2020, 2: 19.

[36] ChenQ, PeiY, TangK, Albu-KayaMG. Structure, extraction, processing, and applications of collagen as an ideal component for biomaterials—a review. Collagen Leather, 2023, 5: 20.

[37] TangC, ZhouK, ZhuY, ZhangW, XieY, WangZ, et al. . Collagen and its derivatives: from structure and properties to their applications in food industry. Food Hydrocolloids, 2022, 131: 107748.

[38] OrgelJPRO, PersikovAV, AntipovaO. Variation in the helical structure of native collagen. PLoS ONE, 2014, 92e89519.

[39] BellaJ. Collagen structure: new tricks from a very old dog. Biochem J, 2016, 47381001-1025.

[40] ShouldersMD, RainesRT. Collagen structure and stability. Annu Rev Biochem, 2009, 781929-958.

[41] ArumugamGKS, SharmaD, BalakrishnanRM, EttiyappanJBP. Extraction, optimization and characterization of collagen from sole fish skin. Sustain Chem Pharm, 2018, 9: 19-26.

[42] KhoshnoodiJ, SigmundssonK, CartaillerJ-P, BondarO, SundaramoorthyM, HudsonBG. Mechanism of chain selection in the assembly of collagen IV: a prominent role for the alpha2 chain. J Biol Chem, 2006, 28196058-6069.

[43] Miller EJ, Collagen types: structure, distribution, and functions. In Collagen, CRC Press: 2018;139−56.

[44] HarringtonWF, Von HippelPH. The structure of collagen and gelatin. Adv Protein Chem, 1962, 16: 1-138.

[45] BellaJ, LiuJ, KramerR, BrodskyB, BermanHM. Conformational effects of Gly-X-Gly interruptions in the collagen triple helix. J Mol Biol, 2006, 3622298-311.

[46] OttaniV, MartiniD, FranchiM, RuggeriA, RaspantiM. Hierarchical structures in fibrillar collagens. Micron, 2002, 337–8587-596.

[47] Wu M, Cronin K, Crane JS. Biochemistry, collagen synthesis. 2018.

[48] WangH. A review of the effects of collagen treatment in clinical studies. Polymers, 2021, 13223868.

[49] FengB, YangH, ZhuM, LiJ, ChangHM, LeungPC, et al. . Collagen-based biomaterials in organoid technology for reproductive medicine: composition, characteristics, and applications. Collagen Leather., 2023, 5: 35.

[50] NaomiR, RidzuanPM, BahariH. Current insights into collagen type I. Polymers, 2021, 13162642.

[51] AvolaR, GrazianoACE, PannuzzoG, BoninaF, CardileV. Hydroxytyrosol from olive fruits prevents blue-light-induced damage in human keratinocytes and fibroblasts. J Cell Physiol, 2019, 23469065-9076.

[52] ZhouY, ZhangY, DaiH, ZhangY, FuY. The potential of undenatured type II collagen against arthritis: a review. Collagen Leather, 2024, 6: 17.

[53] SugitaS, SuzumuraT, NakamuraA, TsukijiS, UjiharaY, NakamuraM. Second harmonic generation light quantifies the ratio of type III to total (I+ III) collagen in a bundle of collagen fiber. Sci Rep, 2021, 11111874.

[54] PizzoHP, HaasM, PuliyandaD. Collagen type III glomerulopathy. Kidney Int, 2018, 192101-106

[55] AbediniaA, NafchiAM, SharifiM, GhalamborP, OladzadabbasabadiN, AriffinF, et al. . Poultry gelatin: characteristics, developments, challenges, and future outlooks as a sustainable alternative for mammalian gelatin. Trends Food Sci Technol, 2020, 104: 14-26.

[56] ZhuS, YuJ, LiuS, DingY, WangW, ZhouX. A bottom-up evaluation on cryoprotective potentials of gelatine from fish scale. Food Hydrocolloids, 2022, 124: 107243.

[57] MakiY, AnnakaM. Gelation of fish gelatin studied by multi-particle tracking method. Food Hydrocolloids, 2020, 101: 105525.

[58] DuconseilleA, AstrucT, QuintanaN, MeersmanF, Sante-LhoutellierV. Gelatin structure and composition linked to hard capsule dissolution: a review. Food Hydrocolloids, 2015, 43: 360-376.

[59] LiY, LuY, ZhaoY, ZhangN, ZhangY, FuY. Deciphering the wound-healing potential of collagen peptides and the molecular mechanisms: a review. J Agric Food Chem, 2024, 724726007-26026.

[60] WangB, XieN, LiB. Influence of peptide characteristics on their stability, intestinal transport, and in vitro bioavailability: a review. J Food Biochem, 2018, 431e12571.

[61] YongjieZ, YanfeiJ, YanZ, WallaceY, JianpingW, SamKCC, et al. . Unveiling a new chapter for collagen peptides: comprehensive insights into oral bioavailability and the enhancement via encapsulation systems. Trends Food Sci Technol, 2024, 156: 104849

[62] DruckerDJ. Advances in oral peptide therapeutics. Nat Rev Drug Discov, 2019, 194277-289.

[63] NongoniermaAB, FitzGeraldRJ. Strategies for the discovery and identification of food protein-derived biologically active peptides. Trends Food Sci Technol, 2017, 69: 289-305.

[64] LarderCE, IskandarMM, KubowS. Collagen hydrolysates: a source of bioactive peptides derived from food sources for the treatment of osteoarthritis. Medicines, 2023, 10950.

[65] AhmadMI, LiY, PanJ, LiuF, DaiH, FuY, et al. . Collagen and gelatin: structure, properties, and applications in food industry. Int J Biol Macromol, 2024, 254: 128037.

[66] SibillaS, GodfreyM, BrewerS, Budh-RajaA, GenoveseL. An overview of the beneficial effects of hydrolysed collagen as a nutraceutical on skin properties: scientific background and clinical studies. Open Nutraceuticals J, 2015, 8129-42.

[67] WuP, ChenL, ChenM, ChiouB-S, XuF, LiuF, et al. . Use of sodium alginate coatings to improve bioavailability of liposomes containing DPP-IV inhibitory collagen peptides. Food Chem, 2023, 414: 135685.

[68] AnselmoAC, GokarnY, MitragotriS. Non-invasive delivery strategies for biologics. Nat Rev Drug Discov, 2019, 18119-40.

[69] DingD, DuB, ZhangC, ZamanF, HuangY. Isolation and identification of an antioxidant collagen peptide from skipjack tuna (Katsuwonus pelamis) bone. RSC Adv, 2019, 94627032-27041.

[70] YangXR, QiuYT, ZhaoYQ, ChiCF, WangB. Purification and characterization of antioxidant peptides derived from protein hydrolysate of the marine bivalve mollusk Tergillarca granosa. Mar Drugs, 2019, 175251.

[71] ByunH-G, KimS-K. Purification and characterization of angiotensin I converting enzyme (ACE) inhibitory peptides from Alaska pollack (Theragra chalcogramma) skin. Process Biochem, 2001, 36121155-1162.

[72] SaigaAI, IwaiK, HayakawaT, TakahataY, KitamuraS, NishimuraT, et al. . Angiotensin I-converting enzyme-inhibitory peptides obtained from chicken collagen hydrolysate. J Agric Food Chem, 2008, 56209586-9591.

[73] WangY, SunY, WangX, WangY, LiaoL, ZhangY, et al. . Novel antioxidant peptides from Yak bones collagen enhanced the capacities of antiaging and antioxidant in Caenorhabditis elegans. J Funct Foods, 2022, 89: 104933.

[74] AlemánA, GiménezB, Pérez-SantínE, Gómez-GuillénMC, MonteroP. Contribution of Leu and Hyp residues to antioxidant and ACE-inhibitory activities of peptide sequences isolated from squid gelatin hydrolysate. Food Chem, 2011, 1252334-341.

[75] Rivero-PinoF, Espejo-CarpioFJ, GuadixEM. Production and identification of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from discarded Sardine pilchardus protein. Food Chem, 2020, 328: 127096.

[76] XiangX, LangM, LiY, ZhaoX, SunH, JiangW, et al. . Purification, identification and molecular mechanism of dipeptidyl peptidase IV inhibitory peptides from discarded shrimp (Penaeus vannamei) head. J Chromatogr B, 2021, 1186: 122990.

[77] ShengY, QiuYT, WangYM, ChiCF, WangB. Novel antioxidant collagen peptides of Siberian sturgeon (Acipenser baerii) cartilages: the preparation, characterization, and cytoprotection of H₂O₂-damaged human umbilical vein endothelial cells (HUVECs). Mar Drugs, 2022, 205325.

[78] ZhangJB, ZhaoYQ, WangYM, ChiCF, WangB. Eight collagen peptides from hydrolysate fraction of Spanish mackerel skins: isolation, identification, and in vitro antioxidant activity evaluation. Mar Drugs, 2019, 174224.

[79] SheihIC, FangTJ, WuTK. Isolation and characterisation of a novel angiotensin I-converting enzyme (ACE) inhibitory peptide from the algae protein waste. Food Chem, 2009, 1151279-284.

[80] TsaiJS, ChenJL, PanBS. ACE-inhibitory peptides identified from the muscle protein hydrolysate of hard clam (Meretrix lusoria). Process Biochem, 2008, 437743-747.

[81] QianZJ, JeJY, KimSK. Antihypertensive effect of angiotensin I converting enzyme-inhibitory peptide from hydrolysates of bigeye tuna dark muscle. Thunnus obesus J Agric Food Chem, 2007, 55218398-8403.

[82] LiuR, ZhouL, ZhangY, ShengNJ, WangZK, WuTZ, et al. . Rapid identification of dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides from Ruditapes philippinarum hydrolysate. Molecules, 2017, 22101714.

[83] ChenM, PanD, ZhouT, GaoX, DangY. Novel umami peptide IPIPATKT with dual dipeptidyl peptidase-IV and angiotensin I-converting enzyme inhibitory activities. J Agric Food Chem, 2021, 69195463-5470.

[84] HouY, ChitrakarB, MaoK, WangK, GuX, GaoJ, et al. . Bioactivity of collagen peptides derived from commercial animals: in silico investigation. LWT, 2023, 187: 115381.

[85] NajafianL, BabjiA. A review of fish-derived antioxidant and antimicrobial peptides: their production, assessment, and applications. Peptides, 2012, 331178-185.

[86] Di BernardiniR, HarnedyP, BoltonD, KerryJ, O’NeillE, MullenAM, et al. . Antioxidant and antimicrobial peptidic hydrolysates from muscle protein sources and by-products. Food Chem, 2011, 12441296-1307.

[87] PalGK, SureshP. Sustainable valorisation of seafood by-products: recovery of collagen and development of collagen-based novel functional food ingredients. Innov Food Sci Emerg Technol, 2016, 37: 201-215.

[88] SongY, FuY, HuangS, LiaoL, WuQ, WangY, et al. . Identification and antioxidant activity of bovine bone collagen-derived novel peptides prepared by recombinant collagenase from Bacillus cereus. Food Chem, 2021, 349: 129143.

[89] YangX, JiaQ, DuanF, HuB, WangM, HeL, et al. . Multiwall carbon nanotubes loaded with MoS₂ quantum dots and MXene quantum dots: non-Pt bifunctional catalyst for the methanol oxidation and oxygen reduction reactions in alkaline solution. Appl Surf Sci, 2019, 464: 78-87.

[90] SarbonNM, BadiiF, HowellNK. Purification and characterization of antioxidative peptides derived from chicken skin gelatin hydrolysate.. Food Hydrocolloids, 2018, 85: 311-320.

[91] FassiniD, WilkieIC, PozzoliniM, FerrarioC, SugniM, RochaMS, et al. . Diverse and productive source of biopolymer inspiration: marine collagens. Biomacromolecules, 2021, 2251815-1834.

[92] ChenX, XiaP, ZhengS, LiY, FangJ, MaZ, et al. . Antioxidant peptides from the collagen of antler ossified tissue and their protective effects against H₂O₂-Induced oxidative damage toward HaCaT Cells. Molecules, 2023, 28196887.

[93] León-LópezA, Fuentes-JiménezL, Hernández-FuentesAD, Campos-MontielRG, Aguirre-ÁlvarezG. Hydrolysed collagen from sheepskins as a source of functional peptides with antioxidant activity. Int J Mol Sci, 2019, 20163931.

[94] BanerjeeP, ShanthiC. Cryptic peptides from collagen: a critical review. Protein Pept Lett, 2016, 237664-672.

[95] NgoDH, RyuB, VoTS, HimayaS, WijesekaraI, KimSK. Free radical scavenging and angiotensin-I converting enzyme inhibitory peptides from Pacific cod (Gadus macrocephalus) skin gelatin. Int J Biol Macromol, 2011, 4951110-1116.

[96] FuY, TherkildsenM, AlukoRE, LametschR. Exploration of collagen recovered from animal by-products as a precursor of bioactive peptides: successes and challenges. Crit Rev Food Sci Nutr, 2019, 59132011-2027.

[97] SinghalP, NigamV, VidyarthiA. Studies on production, characterization and applications of microbial alkaline proteases. Int J Adv Biotechnol Res, 2012, 33653-669

[98] DrydenSV, ShoemakerWG, KimJH. Wound management and nutrition for optimal wound healing. Atlas Oral Maxillofac Surg Clin North Am, 2013, 21137-47.

[99] ZhangW, ChenL, XiongY, PanayiAC, AbududilibaierA, HuY, et al. . Antioxidant therapy and antioxidant-related bionanomaterials in diabetic wound healing. Front Bioeng Biotechnol, 2021, 9: 707479.

[100] XuZ, HanS, GuZ, WuJ. Advances and impact of antioxidant hydrogel in chronic wound healing. Adv Healthc Mater, 2020, 951901502.

[101] ShiS, WangL, SongC, YaoL, XiaoJ. Recent progresses of collagen dressings for chronic skin wound healing. Collagen Leather, 2023, 5: 31.

[102] SubhanF, HussainZ, TauseefI, ShehzadA, WahidF. A review on recent advances and applications of fish collagen. Crit Rev Food Sci Nutr, 2021, 6161027-1037.

[103] ShevchenkoRV, JamesSL, JamesSE. A review of tissue-engineered skin bioconstructs available for skin reconstruction. J R Soc Interface, 2010, 743229-258.

[104] LengQ, LiY, PangX, WangB, WuZ, LuY, et al. . Curcumin nanoparticles incorporated in PVA/collagen composite films promote wound healing. J Drug Deliv, 2020, 2711676-1685.

[105] CaoC, XiaoZ, GeC, WuY. Animal by-products collagen and derived peptide, as important components of innovative sustainable food systems—a comprehensive review. Crit Rev Food Sci Nutr, 2022, 62318703-8727.

[106] JhawarN, WangJV, SaediN. Oral collagen supplementation for skin aging: a fad or the future?. J Cosmet Dermatol, 2020, 194910-912.

[107] DreminV, MarcinkevicsZ, ZherebtsovE, PopovA, GrabovskisA, KronbergaH, et al. . Skin complications of diabetes mellitus revealed by polarized hyperspectral imaging and machine learning. IEEE Trans Med Imaging, 2021, 4041207-1216.

[108] SalzerMC, LafziA, Berenguer-LlergoA, YoussifC, CastellanosA, SolanasG, et al. . Identity noise and adipogenic traits characterize dermal fibroblast aging. Cell, 2018, 17561575-1590.

[109] LiC, FuY, DaiH, WangQ, GaoR, ZhangY. Recent progress in preventive effect of collagen peptides on photoaging skin and action mechanism. Food Sci Hum Wellness, 2022, 112218-229.

[110] YangD, LiuQ, XuQ, ZhengL, ZhangS, LuS, et al. . Effects of collagen hydrolysates on UV-induced photoaging mice: Gly-Pro-Hyp as a potent anti-photoaging peptide. Food Funct, 2024, 1563008-3022.

[111] KobayashiS, OgasawaraN, WatanabeS, YoneyamaY, KirinoS, HiraguriY, et al. . Collagen type I-mediated mechanotransduction controls epithelial cell fate conversion during intestinal inflammation. Inflamm Regen, 2022, 42149.

[112] RanjbarR, GhasemianM, ManiatiM, KhatamiSH, JamaliN, Taheri-AnganehM. Gastrointestinal disorder biomarkers. Clin Chim Acta, 2022, 530: 13-26.

[113] XinXY, ZhouJ, LiuGG, ZhangMY, LiXZ, WangY. Anti-inflammatory activity of collagen peptide in vitro and its effect on improving ulcerative colitis. npj Sci Food, 2025, 911.

[114] MaT, LiC, ZhaoF, CaoJ, ZhangX, ShenX. Effects of co-fermented collagen peptide-jackfruit juice on the immune response and gut microbiota in immunosuppressed mice. Food Chem, 2021, 365: 130487.

[115] RenB, YueK, ZhangY, FuY. Collagen-derived peptides as prebiotics to improve gut health. Curr Opin Food Sci, 2024, 55: 101123.

[116] CareySP, MartinKE, Reinhart-KingCA. Three-dimensional collagen matrix induces a mechanosensitive invasive epithelial phenotype. Sci Rep, 2017, 7142088.

[117] GuoZ, LiuC, HuB, ZhuL, YangY, LiuF, et al. . Simulated gastrointestinal digestion of yak bone collagen hydrolysates and insights into its effects on gut microbiota composition in mice. Food Biosci, 2021, 44: 101463.

[118] ShiH, JiangM, ZhangX, XiaG, ShenX. Characteristics and food applications of aquatic collagen and its derivatives: a review. Food Res Int, 2025, 202: 115531.

[119] WangL, WangQ, QianJ, LiangQ, WangZ, XuJ, et al. . Bioavailability and bioavailable forms of collagen after oral administration to rats. J Agr Food Chem, 2015, 63143752-3756.

[120] MemeteAR, TeusdeaAC, TimarAV, VuscanAN, MintașOS, CavaluS, et al. . Effects of different edible coatings on the shelf life of fresh black mulberry fruits (Morus nigra L.). Agriculture, 2022, 1271068.

[121] da SilvaACP, BarbosaJR, da SilvaAC, BatistaJTS, NevesEMPX, CardosoDNP, et al. . A new edible coating of fish gelatin incorporated into açaí oil to increase the post-harvest shelf life of tomatoes. Food Chem, 2024, 438: 138047.

[122] JiangY, LanW, SameenDE, AhmedS, QinW, ZhangQ, et al. . Preparation and characterization of grass carp collagen-chitosan-lemon essential oil composite films for application as food packaging. Int J Biol Macromol, 2020, 160: 340-351.

[123] MaL, YangX, YangX, LuS, ZhangH, FanY. Stability protection of lutein emulsions by utilizing a functional conjugate of collagen and Lycium barbarum L. leaf flavonoid. Food Res Int, 2024, 176: 113775.

[124] ZhengW, TianE, LiuZ, ZhouC, YangP, TianK, et al. . Small molecule angiotensin converting enzyme inhibitors: a medicinal chemistry perspective. Front Pharmacol, 2022, 13: 968104.

[125] CaoS, WangY, HaoY, ZhangW, ZhouG. Antihypertensive effects in vitro and in vivo of novel angiotensin-converting enzyme inhibitory peptides from bovine bone gelatin hydrolysate. J Agric Food Chem, 2019, 683759-768.

[126] NajafpourR, GhasemiAS, DehghanbanadakiN, MehralitabarH. Computational exploration of naturally derived peptides inhibitory mechanisms against ACE enzyme, from interactions to structural-dynamics. Biochem Biophys Res Commun, 2024, 735: 150812.

[127] ZhengY, WangX, GuoM, YanX, ZhuangY, SunY, et al. . Two novel antihypertensive peptides identified in millet bran glutelin-2 hydrolysates: purification, in silico characterization, molecular docking with ace and stability in various food processing conditions. Foods, 2022, 1191355.

[128] HuangX, FanW, SunJ, YangJ, ZhangY, WangQ, et al. . SARS-CoV-2 induces cardiomyocyte apoptosis and inflammation but can be ameliorated by ACE inhibitor Captopril. Antiviral Res, 2023, 215: 105636.

[129] GuoL, HarnedyPA, ZhangL, LiB, ZhangZ, HouH, et al. . In vitro assessment of the multifunctional bioactive potential of Alaska pollock skin collagen following simulated gastrointestinal digestion. J Sci Food Agric, 2015, 9571514-1520.

[130] FanH, LiaoW, WuJ. Molecular interactions, bioavailability, and cellular mechanisms of angiotensin-converting enzyme inhibitory peptides. J Food Biochem, 2019, 431e12572.

[131] LiY, PanD, ZhangW, XieX, DangY, GaoX. Identification and molecular mechanism of novel ACE inhibitory peptides from broccoli protein. Food Biosci, 2024, 61: 104678.

[132] AlukoRE. Antihypertensive peptides from food proteins. Annu Rev Food Sci Technol, 2015, 61235-262.

[133] AlukoRE. Structure and function of plant protein-derived antihypertensive peptides. Curr Opin Food Sci, 2015, 4: 44-50.

[134] Martínez-AlvarezO, ChamorroS, BrenesA. Protein hydrolysates from animal processing by-products as a source of bioactive molecules with interest in animal feeding: a review. Food Res Int, 2015, 73: 204-212.

[135] ChenJ, SunS, LiY, LiuR. Proteolysis of tilapia skin collagen: identification and release behavior of ACE-inhibitory peptides. LWT-Food Sci Technol, 2021, 139: 110502.

[136] YuZ, WuS, ZhaoW, MiG, DingL, LiJ, et al. . Identification of novel angiotensin I-converting enzyme inhibitory peptide from collagen hydrolysates and its molecular inhibitory mechanism. Int J Food Sci Tech, 2020, 5593145-3152.

[137] IwaniakA, MinkiewiczP, DarewiczM. Food-originating ACE inhibitors, including antihypertensive peptides, as preventive food components in blood pressure reduction. Compr Rev Food Sci Food Saf, 2014, 132114-134.

[138] HerregodsG, Van CampJ, MorelN, GhesquièreB, GevaertK, VercruysseL, et al. . Angiotensin I-converting enzyme inhibitory activity of gelatin hydrolysates and identification of bioactive peptides. J Agric Food Chem, 2011, 592552-558.

[139] AlemánA, Gómez-GuillénM, MonteroP. Identification of ace-inhibitory peptides from squid skin collagen after in vitro gastrointestinal digestion. Food Res Int, 2013, 541790-795.

[140] ZhuangY, SunL, ZhangY, LiuG. Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema esculentum) collagen peptides on renovascular hypertension. Mar Drugs, 2012, 102417-426.

[141] LeeJK, JeonJ-K, ByunH-G. Antihypertensive effect of novel angiotensin I converting enzyme inhibitory peptide from chum salmon (Oncorhynchus keta) skin in spontaneously hypertensive rats. J Funct Foods, 2014, 7: 381-389.

[142] AyatiS, EunJB, AtoubN, Mirzapour-KouhdashtA. Functional yogurt fortified with fish collagen-derived bioactive peptides: antioxidant capacity, ACE and DPP-IV inhibitory. J Food Process Preserv, 2022, 461e16208.

[143] Holm NielsenS, EdsfeldtA, TengrydC, GustafssonH, ShoreAC, NataliA, et al. . The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis. J Intern Med, 2021, 2901179-189.

[144] CamA, de MejiaEG. Role of dietary proteins and peptides in cardiovascular disease. Mol Nutr Food Res, 2012, 56153-66.

[145] JaliliZ, JaliliF, MoradiS, BagheriR, MoosavianSP, NaeiniF, et al. . Effects of collagen peptide supplementation on cardiovascular markers: a systematic review and meta-analysis of randomised, placebo-controlled trials. Br J Nutr, 2023, 1295779-794.

[146] NikolovA, PopovskiN. Extracellular matrix in heart disease: focus on circulating collagen type I and III derived peptides as biomarkers of myocardial fibrosis and their potential in the prognosis of heart failure: a concise review. Metabolites, 2022, 124297.

[147] WuS, SunJ, TongZ, LanX, ZhaoZ, LiaoD. Optimization of hydrolysis conditions for the production of angiotensin-I converting enzyme-inhibitory peptides and isolation of a novel peptide from lizard fish (Saurida elongata) muscle protein hydrolysate. Mar Drugs, 2012, 1051066-1080.

[148] HashimP, RidzwanMM, BakarJ, HashimMD. Collagen in food and beverage industries. Int Food Res J, 2015, 2211

[149] CuiP, ShaoT, LiuW, LiM, YuM, ZhaoW, et al. . Advanced review on type II collagen and peptide: preparation, functional activities and food industry application. Crit Rev Food Sci Nutr, 2024, 643011302-11319.

[150] JacquesE, HosoyamaK, BiniamB, Eren CimenciC, SedlakovaV, SteevesAJ, et al. . Collagen-based microcapsules as therapeutic materials for stem cell therapies in infarcted myocardium. ACS Biomater Sci Eng, 2020, 684614-4622.

[151] PastorinoL, ErokhinaS, KonovalovO, BianchiniP, DiasproA, RuggieroC. Permeability variation study in collagen-based polymeric capsules. BioNanoScience, 2011, 1: 192-197.

[152] Vargas-MunozDP, de OliveiraLAN, da SilvaLC, GodoyHT, KurozawaLE. Storage stability of 5-caffeoylquinic acid in powdered cocona pulp microencapsulated with hydrolyzed collagen and maltodextrin blend. Food Res Int, 2020, 137: 109652.

[153] RajabiH, GhorbaniM, JafariSM, MahoonakAS, RajabzadehG. Retention of saffron bioactive components by spray drying encapsulation using maltodextrin, gum Arabic and gelatin as wall materials. Food Hydrocolloids, 2015, 51: 327-337.

[154] PowerO, NongoniermaAB, JakemanP, FitzgeraldRJ. Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes. Proc Nutr Soc, 2014, 73134-46.

[155] RitianJ, TengX, LiaoM, ZhangL, WeiZ, MengR, et al. . Release of dipeptidyl peptidase IV inhibitory peptides from salmon (Salmo salar) skin collagen based on digestion-intestinal absorption in vitro. Int J Food Sci Tech, 2021, 5673507-3518.

[156] SaeediP, PetersohnI, SalpeaP, MalandaB, KarurangaS, UnwinN, et al. . Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes atlas. Diabetes Res Clin Pract, 2019, 157: 107843.

[157] AcquahC, DzuvorCK, ToshS, AgyeiD. Anti-diabetic effects of bioactive peptides: recent advances and clinical implications. Crit Rev Food Sci Nutr, 2022, 6282158-2171.

[158] JinR, TengX, ShangJ, WangD, LiuN. Identification of novel DPP–IV inhibitory peptides from Atlantic salmon (Salmo salar) skin. Food Res Int, 2020, 133: 109161.

[159] LiuR, ChengJ, WuH. Discovery of food-derived dipeptidyl peptidase IV inhibitory peptides: a review. Int J Mol Sci, 2019, 203463.

[160] MakrilakisK. The role of DPP-4 inhibitors in the treatment algorithm of type 2 diabetes mellitus: when to select, what to expect. Int J Environ Res Public Health, 2019, 16152720.

[161] UnnikrishnanP, SuthindhiranK, JayasriM. Antidiabetic potential of marine algae by inhibiting key metabolic enzymes. Front Life Sci, 2015, 82148-159.

[162] TawalbehD, Kha’simMI, Mhd SarbonN, SarbonNM. Techno-functional and bioactivity properties of collagen hydrolysate and peptide: a review. Food Rev Int, 2025.

[163] ZhangY, ChenR, ChenX, ZengZ, MaH, ChenS. Dipeptidyl peptidase IV-inhibitory peptides derived from silver carp (Hypophthalmichthys molitrix Val.) proteins. J Agric Food Chem, 2016, 644831-839.

[164] WangB, YuZ, YokoyamaW, ChiouB-S, ChenM, LiuF, et al. . Collagen peptides with DPP-IV inhibitory activity from sheep skin and their stability to in vitro gastrointestinal digestion. Food Biosci, 2021, 42: 101161.

[165] HuangSL, HungCC, JaoCL, TungYS, HsuKC. Porcine skin gelatin hydrolysate as a dipeptidyl peptidase IV inhibitor improves glycemic control in streptozotocin-induced diabetic rats. J Funct Foods, 2014, 11: 235-242.

[166] DavyA, ThomsenKK, JulianoMA, AlvesLC, SvendsenI, SimpsonDJ. Purification and characterization of barley dipeptidyl peptidase IV. J Plant Physiol, 2000, 1222425-432.

[167] NongoniermaAB, FitzGeraldRJ. Dipeptidyl peptidase IV inhibitory and antioxidative properties of milk protein-derived dipeptides and hydrolysates. Peptides, 2013, 39: 157-163.

[168] NongoniermaAB, FitzGeraldRJ. An in silico model to predict the potential of dietary proteins as sources of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides. Food Chem, 2014, 165: 489-498.

[169] HatanakaT, KawakamiK, UrajiM. Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-IV activity. J Enzyme Inhib Med Chem, 2014, 296823-828.

[170] HsiehC, WangT, HungC, ChenM, HsuK. Improvement of glycemic control in streptozotocin-induced diabetic rats by Atlantic salmon skin gelatin hydrolysate as the dipeptidyl-peptidase IV inhibitor. Food Funct, 2015, 661887-1892.

[171] ZhuC-F, LiG-Z, PengH-B, ZhangF, ChenY, LiY. Treatment with marine collagen peptides modulates glucose and lipid metabolism in Chinese patients with type 2 diabetes mellitus. Appl Physiol Nutr Metab, 2010, 356797-804.

[172] DevasiaS, KumarS, StephenaP, InoueN, SugiharaF, KoizumiS, et al. . A double blind, randomised, four arm clinical study to evaluate the safety, efficacy and tolerability of collagen peptide as a nutraceutical therapy in the management of type II diabetes mellitus. J Diabetes Metab Disord, 2020, 1011839

[173] OjedaMJ, Cereto-MassaguéA, VallsC, PujadasG, PujadasG. DPP-IV, an important target for antidiabetic functional food design. Foodinform Appl Chem Inf Food Chem, 2014.

[174] YangY, HuangL, HuangZ, RenY, XiongY, XuZ, et al. . Food-derived peptides unleashed: emerging roles as food additives beyond bioactivities. Crit Rev Food Sci Nutr, 2024.

[175] LacroixIM, Li-ChanEC. Food-derived dipeptidyl-peptidase IV inhibitors as a potential approach for glycemic regulation-Current knowledge and future research considerations. Trends Food Sci Technol, 2016, 54: 1-16.

[176] ZhangM, ZhuL, WuG, LiuT, QiX, ZhangH. Food-derived dipeptidyl peptidase IV inhibitory peptides: production, identification, structure-activity relationship, and their potential role in glycemic regulation. Crit Rev Food Sci Nutr, 2024, 6482053-2075.

Funding

National Key R&D Program of China(2022YFA0912800)

National Excellent Young Scientists Fund(00308054A1045)

National Natural Science Foundation of China(22178233)

State Key Laboratory of Polymer Materials Engineering(sklpme 2020−03−01)

Tianfu Emei Program of Sichuan Province(2022-EC02-00073-CG)

Postdoctoral Special Funding of Sichuan Province(TB2022063)

Postdoctoral Funding of Sichuan University (2022SCU12099)

Talents Program of Sichuan Province

Double First-Class University Plan of Sichuan University

RIGHTS & PERMISSIONS

The Author(s)