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乳源生物活性肽是潜藏于乳蛋白序列中的天然功能片段,通常由2~20个氨基酸残基组成,经胃肠道消化、体外酶解或微生物发酵等途径释放,具有多种生理调节功能。该文系统综述了乳源生物活性肽的研究进展,重点论述了其分离纯化、结构鉴定、功能活性及作用机制。在制备与分离层面,酶解工艺是定向释放活性肽的基础,而超滤、纳滤及多维色谱联用技术则是从复杂水解物中实现高效纯化的关键。在结构鉴定方面,液相色谱-串联质谱已成为解析肽段一级结构的核心技术,结合分子对接等计算机模拟技术,能够深入阐释其构效关系。最后,该文总结了乳源生物活性肽的抗氧化、血管紧张素转化酶(angiotensin-converting enzyme,ACE)抑制、抗菌、免疫调节、阿片样及促进矿物质吸收等多种功能。尽管部分乳源活性肽已展现出商业化应用前景,但其研究仍面临体内生物利用度低等挑战。未来研究应致力于通过人工智能辅助理性设计、构建新型递送系统,以推动乳源生物活性肽在功能食品和精准营养领域的深度开发与高值化应用。
Abstract:Milk-derived bioactive peptides(MBPs) are natural functional fragments encrypted within the primary structures of milk proteins.Typically consisting of 2~20 amino acid residues, they are released through gastrointestinal digestion, enzymatic hydrolysis in vitro, or microbial fermentation, and exhibit a wide range of physiological regulatory functions.This review systematically summarizes recent advances in the study of MBPs, with a focus on their isolation and purification, structural identification, functional activities, and underlying mechanisms.Regarding preparation and separation, enzymatic hydrolysis serves as the basis for the targeted release of bioactive peptides, while techniques such as ultrafiltration, nanofiltration, and multidimensional chromatography are critical for achieving high-efficiency purification from complex hydrolysates.For structural identification, liquid chromatographytandem mass spectrometry has emerged as the core technology for deciphering the primary structures of peptides.When combined with computational simulations such as molecular docking, it enables an in-depth exploration of their structure-activity relationships.Research has demonstrated that MBPs possess diverse bioactivities, including antioxidant, angiotensin-converting enzyme inhibitory, antimicrobial, immunomodulatory, opioid-like, and mineralbinding properties.Although some MBPs have shown promising potential for commercial applications, several challenges remain, such as low bioavailability in vivo.Future research should focus on rational peptide design assisted by artificial intelligence, the development of novel delivery systems, and the implementation of rigorous clinical intervention studies to promote the deeper development and high-value application of MBPs in the fields of functional foods and precision nutrition.
[1]TABRIZI S H,HADDAD E,SABATéJ.The presence of lunasin,a soy-derived bioactive peptide in plasma:a randomized clinical trial[J].Current developments in nutrition,2020,4:nzaa045_33.
[2]席丽琴,杨君娜,李家鹏,等.动物源免疫活性肽的制备及功能评价研究进展[J].肉类研究,2023,37(10):49-56.
[3]SALVADOR D,ACOSTA Y,ZAMORA A,et al.Rennet-induced casein micelle aggregation models:a review[J].Foods,2022,11:1243.
[4]PARK Y W,NAM M S.Bioactive peptides in milk and dairy products:a review[J].Food science of animal resources,2015,35(06):831-40.
[5]PINA A S,ROQUE A C A.Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzyme[J].Journal of molecular recognition,2009,22(02):162-168.
[6]魏光强,施娅楠,万长江,等..基于模拟胃肠道消化的云南民族乳制品蛋白肽研究[J].食品科学,2021,42(01):208-214.
[7]姚婷婷,赵培城,顾东杰.酶解乳蛋白制取乳源肽的研究[J].粮食与食品工业,2006(02):29-32.
[8]李思怡,姜雨彤,妥彦峰,等.微生物发酵法制备乳源生物活性肽研究进展[J].食品科学,2023,44(21):312-329.
[9]吴相佚,刘泽朋,高婧昕,等.超高压处理对乳蛋白结构和致敏性的改善作用[J].中国食品学报,2022,22(07):142-148.
[10]任国谱,余兵.酶解乳清浓缩蛋白WPC80制备乳清肽的研究[J].食品科学,2010,31(20):11-14.
[11]赵瑾德,韩望,武俊瑞,等.基于肽组学与人工智能挖掘乳酸菌源功能活性肽研究进展[J/OL].食品与发酵工业,1-11[2025-10-15].https://doi.org/10.13995/j.cnki.11-1802/ts.043629.
[12]DHENIN J,DUPRéM,DRUART K,et al.A multiparameter optimization in middle-down analysis of monoclonal antibodies by LC-MS/MS[J].Journal of mass spectrometry,2023,58(03):e4909.
[13]张昱婷,牛占占,黄玉清,等.畜禽内脏源生物活性肽的制备、活性分析及构效关系的研究进展[J].现代食品科技,2024,40(07):343-352.
[14]赵立娜,汪少芸,黄一帆.乳清蛋白生物活性肽及其应用前景[J].食品科学技术学报,2014,32(03):48-53.
[15]朱一,武俊瑞,纪帅奇,等,乳源活性肽在功能性食品中的应用[J].中国乳品工业,2024,52(10);47-51.
[16]赵烜影,刘振民,雍靖怡,等.乳源生物活性肽研究进展[J].乳业科学与技术,2021,44(06):51-57.
[17]王凤翼,季瑛.乳蛋白肽及其在食品中的应用[J].中国乳业,2001(05);64-65.
[18]田俊英,潘道东,郭宇星.瑞士乳杆菌蛋白酶水解酪蛋白制备血管紧张素转化酶抑制肽的条件优化[J].食品科学,2009,30(11):170-174.
[19]HAO L,LI X,ZHAO B,et al.Enzymatic hydrolysis optimization of Yak Whey protein concentrates and bioactivity evaluation of the ultrafiltered peptide fractions[J].Molecules,2024,29(06):1403.
[20]KAUR S,VASILJEVIC T,HUPPERTZ T.Milk Protein hydrolysis by actinidin-kinetic and thermodynamic characterisation and comparison to bromelain and papain[J].Foods,2023,12:4248.
[21]矫春娜,张健,刘芳,等.体外模拟消化在水产品营养活性物质研究中的应用进展[J],食品工业科技,2023,44(08):421-428.
[22]陈心瑷,翟兴月,佟长青,等,生物活性肽和肠道菌群相互作用研究进展[J].食品安全质量检测学报,2022,1304);1044-1049.
[23]ZHAO X,CHENG Y,XU J,et al.Dopamine-modified hydrated silica immobilized flavourzyme for efficient bioactive peptide release from β-lactoglobulin[J].Food chemistry,2025,487:144725.
[24]曾庆祝,许庆陵,黄儒强,等.血管紧张素转换酶抑制肽的分离[J].水产学报,2007,31(06):818-824.
[25]王国荣,张列兵,于景华,等.优先酶解乳清蛋白浓缩物中β-乳球蛋白工艺的研究[J],中国乳品工业,2007(10):4-7.
[26]张树利,滕国新,曹万旭.纳滤技术脱盐和浓缩乳清的研究[J].中国乳品工业,2009,37(08):15-17.
[27]LONG R,LU S,CHEN X,et al.Human milk peptide MAMP-1 alleviates necrotizing enterocolitis via inhibition of the TLR4-mediated PI3K-AKT-NF-κB signaling pathway[J].Food&function,2025,16(10):3904-3917.
[28]迟晓星,张涛.乳中蛋白肽提取工艺研究[J].食品科技,2008(03):187-189.
[29]NIETO-VELOZA A,ZHONG Q,KIM W S,et al.Utilization of tofu processing wastewater as a source of the bioactive peptide lunasin[J].Food chemistry,2021,362:130220.
[30]GIRGIH A T,UDENIGWE C C,ALUKO R E.Reverse-phase HPLC separation of hemp seed(Cannabis sativa L.)protein hydrolysate produced peptide fractions with enhanced antioxidant capacity[J].Plant foods for human nutrition,2013,68(01):39-46.
[31]KIM S,LIM S D.Separation and purification of lipase inhibitory peptide from fermented milk by Lactobacillus plantarum Q180[J].Food science of animal resources,2020,40(01):87-95.
[32]MEDZIHRADSZKY K F,CHALKLEY R J.Lessons in de novo peptide sequencing by tandem mass spectrometry[J].Mass spectrometry reviews,2015,34(01):43-63.
[33]NIELSEN S D,PURUP S,LARSEN L B.Effect of casein hydrolysates on intestinal cell migration and their peptide profiles by LC-ESI/MS/MS[J].Foods,2019,8(03):91.
[34]LIANG N,BEVERLY R L,SCOTTOLINE BP.et al.Peptides derived from in vitro and in vivo digestion of human milk are immunomodulatory in THP-1 human macrophages[J].The journal of nutrition,2022,152(01):331-342.
[35]IRAM D,SANSI M S,ZANAB S,et al.Insilico identification of antidiabetic and hypotensive potential bioactive peptides from the sheep milk proteins:a molecular docking study[J].Journal of food biochemistry,2022,46(11):el4137.
[36]侯成杰,聂彩清,王彦茜,等.α-乳白蛋白源ACE抑制肽快速筛选及验证[J].食品科学,2021,42(24):100-107.
[37]BANIC M,BUTORAC K,CULJAK N,et al.An Integrated comprehensive peptidomics and in silico analysis of bioactive peptide-rich milk fermented by three autochthonous cocci strains[J].International journal of molecular sciences,2024,25(04):2431.
[38]任娇艳,王敏,侯传丽,等.食源性肽的功能特性评价方法,分子构效关系及吸收代谢机制[J].食品科学技术学报,2023,41(02):7-22.
[39]LIANG Y,ZU X Y,ZHAO Y N,et al.Research on the synergistic inhibition of angiotensin-converting enzyme(ACE)by the gastrointestinal digestion products of the ACE inhibitory peptide FPPDVA[J].Journal of agricultural and food chemistry,2024,72(44):24463-24475.
[40]孙振刚,武文起,冯永强,等.α2-f(56-57):YS的ACE活性抑制作用及在酸奶中的应用[J].食品研究与开发,2015(08):15-29.
[41]YAGO T,YUDA N,TANAKA M,et al.Evaluating intestinal absorption of peptide Met-Lys-Pro in casein hydrolysate using Caco-2 and human iPS cell-derived small intestinal epithelial cells[J].Food research international,2024,193:114831.
[42]XIE N,WANG B,JIANG L,et al.Hydrophobicity exerts different effects on bioavailability and stability of antioxidant peptide fractions from casein during simulated gastrointestinal digestion and Caco-2 cell absorption[J].Food research international,2015,76:518-526.
[43]MOHANTA O,DAS P K,PANDA S S,et al.Anti-inflammatory activity of Leonotis nepetifolia leaf essential oil in LPS-stimulated RAW 264.7 cells and its molecular mechanism of action[J].Scientific reports,2025,15(01):32978.
[44]ZHENG W,LI Y,WANG Y,et al.Identification of a novel peptide with anti-inflammatory activity from Binglangjiang buffalo fermented milk and its potential inhibitory mechanism in lipopolysacchande-stimulated RAW 264.7 cells[J].Food chemistry,2025,468:142451.
[45]MOREIRA T S,ANTUNES V R,FALQUETTO B,et al.Long-term stimulation of cardiac vagal preganglionic neurons reduces blood pressure in the spontaneously hypertensive rat[J].Journal of hypertension,2018,36(12):2444-2452.
[46]马丽艳,胡昂,刘志东,等.扇贝抗氧化肽对衰老小鼠体内抗氧化活性研究[J].食品安全质量检测学报,2018,9(19):5159-5163.
[47]王豪,苏米亚,孙克杰,等.食源性抗氧化肽研究进展[J].天然产物研究与开发,2012,24(11):1680-1689.
[48]陈月华,程云辉,许宙,等.食源性生物活性肽免疫调节功能研究进展[J].食品与机械,2016,32(05):209-213.
[49]CHU N H S,LING J,POON E W M,et al.Combining a diet rich in fermentable carbohydrates with metformin improves glycaemic control and reshapes the gut microbiota in people with prediabetes[J].Nature metabolism,2025,7(08):1614-1629.
[50]于洋,祁艳霞,靳艳.乳源生物活性肽研究进展[J].食品与发酵工业,2017,43(09):259-266.
[51]娄肖肖,马洪鹏,高姣姣,等.乳源生物活性肽生物学功能研究进展[J].乳业科学与技术,2024,47(04):31-37.
[52]陈苏婉,汤颖秀,代春华,等.副干酪乳杆菌发酵制备牛乳抗氧化肽饮料工艺优化[J].乳业科学与技术,2017,40(05):1-7.
[53]SUETSUNA K,UKEDA H,OCHI H.Isolation and characterization of free radical scavenging activities peptides derived from casein[J].Journal of nutritional biochemistry,2000,11(03):128-131.
[54]WAILI Y,GAHAFU Y,AOBULITALIFU A,et al.Isolation,purification,and characterization of antioxidant peptides from fresh mare's milk[J].Food science and nutrition,2021,9:4018-4027.
[55]凌玉芳,卢蓉蓉,孙震,等.乳清蛋白酶解物对PC12细胞氧化损伤防护作用的体外研究[J].营养学报,2011,33(02):162-166.
[56]张红玉,李会珍,张天伟,等.抗氧化肽作用机制研究进展[J].食品安全质量检测学报,2022,13(12):3981-3988,
[57]涂茂林.牛乳酪蛋白抗血栓和降血压活性肽的筛选及结构表征[D].哈尔滨:哈尔滨工业大学,2019.
[58]RUTELLA G S,SOLIERI L,MARTINI S,et al.Release of the antihypertensive tripeptides valine-proline-proline and isoleucine-proline-proline from bovine milk caseins during in vitro gastrointestinal digestion[J].Journal of agricultural and food chemistry,2016,64(45):8509-8515.
[59]XUE L,WANG X,HU Z,et al.Identification and characterization of anangiotensin-converting enzyme inhibitory peptide derived from bovine casein[J].Peptides,2018:161-168.
[60]马莹.乳清蛋白源ACE抑制肽的分离纯化与结构鉴定[D].天津:天津商业大学,2019.
[61]CHEN L,SHANGGUAN W F,BAO C J,et al.Collaborative optimization and molecular docking exploration of novel ACE-inhibitory peptides from bovine milk by complex proteases hydrolysis[J].Artificial cells,nanomedicine,and biotechnology,20 20,48(01):180-187.
[62]陈舒柔,许华根,潘家丽,等.乳源性血管紧张素转换酶抑制肽的研究进展[J].食品工业科技,2023,44(20):422-430.
[63]宋萌佳,宇光海,潘龙,等.牛乳酪蛋白源生物活性肽的研究进展[J].中国调味品,2024,49(07):214-220.
[64]OUERTANI A,CHAABOUNI I,MOvSBAH A,et al.Two new secreted proteases generate a casein-derived antimicrobial peptide in Bacillus cereus food born isolate leading to bacterial competition in milk[J].Frontiers in microbiology,2018,9:1148
[65]QI S,ZHAO S,ZHANG H,et al.Novel casein antimicrobial peptides for the inhibition of oral pathogenic bacteria[J].Food chemistry,2023,425:136454.
[66]OMIDBAKHSH A E,FARMANI J,RAFTANI A Z,et al.Antimicrobial activity,environmental sensitivity,mechanism of action,and food application of αS165-181 peptide[J].International journal of food microbiology,2021,358:109403.
[67]THEOLIER J,HAMMAMI R,LABELLE P,et al.Isolation and identification of antimicrobial peptides derived by peptic cleavage of whey protein isolate[J].Journal of functional foods,2013:5(02):706-714.
[68]罗晓,蔡欣阳,吴慧艳,等.抗菌肽作用机制研究进展[J/OL].微生物学通报,1-29[2025-10-09].https://doi.org/10.13344/j.microbiol.china.250501.
[69]MIGLIORE-SAMOUR D,FLOC'H F,JOLLES P.Biologically active casein peptides implicated in immunomodulation[J].Journal of dairy research,1989,56(03):357-362.
[70]KITAZAWA H,YONEZAWA K,TOHNO M,et al.Enzymatic digestion of the milk protein beta-casein releases potent chemotactic peptide(s)for monocytes and macrophages[J].International immunopharmacology,2007,7(09):1150-1159.
[71]LIU B,QIAO W,ZHANG M,et al.Bovine milk with variant β-casein types on immunological mediated intestinal changes and gut health of mice[J].Frontiers in nutrition,2022,9:970685.
[72]CHEN Y,XU L,LAN Y,et al.Four novel sleep-promoting peptides screened and identified from bovine casein hydrolysates using a patch-clamp model in vitro and Caenorhabditis elegans in vivo[J].Food function,2023,14(13):6142-6156.
[73]QIAN J,ZHENG L,SU G,et al.Identification and screening of potential bioactive peptides with sleep-enhancing effects in bovine milk casein hydrolysate[J].Journal of agricultural and food chemistry,20 21,69(38):11246-112 58.
[74]BEHERA P,KUMAR R,SANDEEP I V R,et al.Casein hydrolysates enhance osteoblast proliferation and differentiation in mouse bone marrow culture[J].Food bioscience,2013,2:24-30.
[75]REDDI S,KUMAR N,VIJ R,et al.Akt drives buffalo caseinderived novel peptide-mediated osteoblast differentiation[J].Journal of nutritional biochemistry,2016,38:134-144.
基本信息:
DOI:10.13478/j.cnki.jasyu.2025.04.001
中图分类号:TS252.1
引用信息:
[1]李依璇,孙亚楠,赵昌成,等.乳源生物活性肽的分离鉴定技术、功能特性及作用机制研究进展[J].延边大学农学学报,2025,47(04):1-9.DOI:10.13478/j.cnki.jasyu.2025.04.001.