{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:10:37Z","timestamp":1790176237381,"version":"4.1.0"},"reference-count":43,"publisher":"American Chemical Society (ACS)","issue":"37","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A growing body of literature reports the health benefits of the jellyfish collagen hydrolysate. However, although hydroxyproline (Hyp)-containing oligopeptides absorbed into the bloodstream are considered responsible for the biological functions of collagen hydrolysate, the active ingredient specific to jellyfish collagen remains unclear. Here, we revealed that a collagenase-digested cannonball jellyfish collagen hydrolysate is highly enriched with a bioactive tripeptide, Gly-3Hyp-4Hyp (15.6 mg\/g). In humans, oral ingestion of the jellyfish collagen hydrolysate resulted in a 7.8-fold higher blood absorption of Gly-3Hyp-4Hyp than that of ingesting bovine collagen hydrolysate. Remarkably, its concentration surpassed that of Pro-Hyp, which is conventionally the predominant blood-absorbable peptide. Furthermore, in mice, Gly-3Hyp-4Hyp was efficiently delivered to the skin after jellyfish collagen hydrolysate administration, showing a 19-fold greater accumulation compared with the bovine group, whereas other Hyp-containing oligopeptides exhibited minimal transport. This remarkable bioavailability and effective tissue delivery suggest that Gly-3Hyp-4Hyp is a major candidate driving the biological functions of the jellyfish collagen hydrolysate.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c08326","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:02:11Z","timestamp":1788879731000},"page":"29328-29337","source":"Crossref","is-referenced-by-count":0,"title":["Oral Ingestion\nof Jellyfish Collagen Hydrolysate Effectively\nDelivers a Bioactive Tripeptide, Gly-3Hyp-4Hyp, into the Blood and\nSkin"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9100-758X","authenticated-orcid":true,"given":"Yuki","family":"Taga","sequence":"first","affiliation":[{"name":"Nippi Research Institute of Biomatrix , Kuwabara 520-11, Toride , ,","place":["Ibaraki, Japan, 302-0017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Nippi Research Institute of Biomatrix , Kuwabara 520-11, Toride , ,","place":["Ibaraki, Japan, 302-0017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Kusubata","sequence":"additional","affiliation":[{"name":"Nippi Research Institute of Biomatrix , Kuwabara 520-11, Toride , ,","place":["Ibaraki, Japan, 302-0017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Nippi Research Institute of Biomatrix , Kuwabara 520-11, Toride , ,","place":["Ibaraki, Japan, 302-0017"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"issue":"2","key":"2026092310083912700_cit1","doi-asserted-by":"publisher","first-page":"106","DOI":"10.3109\/10409231003627991","article-title":"Prolyl 4-hydroxylase","volume":"45","author":"Gorres","year":"2010","journal-title":"Crit. 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Plus"},{"key":"2026092310083912700_cit3","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-443-19141-1.00003-0","article-title":"Oral bioaccessibility\nand bioavailability of protein hydrolysates and bioactive peptides\nderived from food sources","volume-title":"Protein Digestion-Derived\nPeptides","author":"Sato","year":"2024"},{"issue":"16","key":"2026092310083912700_cit4","doi-asserted-by":"publisher","first-page":"6531","DOI":"10.1021\/jf050206p","article-title":"Identification of food-derived\ncollagen\npeptides in human blood after oral ingestion of gelatin hydrolysates","volume":"53","author":"Iwai","year":"2005","journal-title":"J. Agric. Food Chem."},{"issue":"33","key":"2026092310083912700_cit5","doi-asserted-by":"publisher","first-page":"8737","DOI":"10.1021\/acs.jafc.8b03648","article-title":"Characterization of\nangiotensin-converting enzyme inhibitory activity of X-Hyp-Gly-type\ntripeptides: Importance of collagen-specific prolyl hydroxylation","volume":"66","author":"Taga","year":"2018","journal-title":"J. Agric. Food Chem."},{"issue":"9","key":"2026092310083912700_cit6","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1080\/10408398.2015.1038377","article-title":"Biological\neffect of hydrolyzed collagen on bone metabolism","volume":"57","author":"Daneault","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"issue":"4","key":"2026092310083912700_cit7","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/s40744-020-00240-5","article-title":"Role of collagen derivatives in osteoarthritis and\ncartilage repair: A systematic scoping review with evidence mapping","volume":"7","author":"Honvo","year":"2020","journal-title":"Rheumatol. Ther"},{"issue":"12","key":"2026092310083912700_cit8","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1111\/ijd.15518","article-title":"Effects of hydrolyzed\ncollagen supplementation on skin aging: a systematic review and meta-analysis","volume":"60","author":"de Miranda","year":"2021","journal-title":"Int. J. Dermatol."},{"issue":"4\u20135","key":"2026092310083912700_cit9","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3109\/03008207.2013.800867","article-title":"Collagen prolyl 3-hydroxylation: a major role for a\nminor post-translational modification?","volume":"54","author":"Hudson","year":"2013","journal-title":"Connect.\nTissue Res."},{"issue":"1","key":"2026092310083912700_cit10","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s41538-022-00144-4","article-title":"Identification\nof a highly stable\nbioactive 3-hydroxyproline-containing tripeptide in human blood after\ncollagen hydrolysate ingestion","volume":"6","author":"Taga","year":"2022","journal-title":"npj Sci. Food"},{"key":"2026092310083912700_cit11","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.foodchem.2015.09.094","article-title":"Nutritional\ncomposition and total\ncollagen content of three commercially important edible jellyfish","volume":"196","author":"Khong","year":"2016","journal-title":"Food Chem."},{"key":"2026092310083912700_cit12","doi-asserted-by":"publisher","first-page":"104206","DOI":"10.1016\/j.tifs.2023.104206","article-title":"The emergence\nof jellyfish collagen: A comprehensive review on research progress,\nindustrial applications, and future opportunities","volume":"141","author":"Chiarelli","year":"2023","journal-title":"Trends Food Sci. Technol."},{"issue":"1","key":"2026092310083912700_cit13","doi-asserted-by":"publisher","first-page":"a004978","DOI":"10.1101\/cshperspect.a004978","article-title":"The collagen\nfamily","volume":"3","author":"Ricard-Blum","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2026092310083912700_cit14","doi-asserted-by":"publisher","first-page":"100786","DOI":"10.1016\/j.mtbio.2023.100786","article-title":"Extracellular matrix\ntype 0: From ancient collagen lineage to a versatile product pipeline\n- JellaGelTM","volume":"22","author":"Faruqui","year":"2023","journal-title":"Mater. Today Bio"},{"issue":"1","key":"2026092310083912700_cit15","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3390\/nu5010223","article-title":"Effects of collagen and collagen\nhydrolysate from jellyfish umbrella on histological and immunity changes\nof mice photoaging","volume":"5","author":"Fan","year":"2013","journal-title":"Nutrients"},{"issue":"2","key":"2026092310083912700_cit16","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3390\/md10020417","article-title":"Antihypertensive effect of long-term\noral administration of jellyfish (Rhopilema esculentum) collagen peptides\non renovascular hypertension","volume":"10","author":"Zhuang","year":"2012","journal-title":"Mar. Drugs"},{"issue":"1","key":"2026092310083912700_cit17","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.cjtee.2018.10.004","article-title":"The wound\nhealing potential of collagen peptides derived from the jellyfish\nRhopilema esculentum","volume":"22","author":"Felician","year":"2019","journal-title":"China J. Orthop. Traumatol."},{"issue":"5","key":"2026092310083912700_cit18","doi-asserted-by":"publisher","first-page":"01","DOI":"10.31579\/2690-1919\/532","article-title":"Effects of a jellyfish collagen-based amino acid supplement\non cognitive function and memory: a pilot investigation","volume":"19","author":"E. Wolkodoff","year":"2025","journal-title":"J. Clin. Res. Rep."},{"issue":"28","key":"2026092310083912700_cit19","doi-asserted-by":"publisher","first-page":"15352","DOI":"10.1016\/S0021-9258(18)95743-1","article-title":"Jellyfish mesogloea collagen. Characterization of molecules\nas alpha 1 alpha 2 alpha 3 heterotrimers","volume":"260","author":"Miura","year":"1985","journal-title":"J.\nBiol. Chem."},{"issue":"1","key":"2026092310083912700_cit20","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3945\/jn.109.116228","article-title":"Current in vitro testing\nof bioactive peptides is not valuable","volume":"140","author":"Foltz","year":"2010","journal-title":"J. Nutr."},{"issue":"10","key":"2026092310083912700_cit21","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1093\/jn\/129.10.1891","article-title":"Oral administration\nof (14)C labeled gelatin hydrolysate leads to an accumulation of radioactivity\nin cartilage of mice (C57\/BL)","volume":"129","author":"Oesser","year":"1999","journal-title":"J. Nutr."},{"issue":"2","key":"2026092310083912700_cit22","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1021\/jf9031487","article-title":"Absorption\nand effectiveness of orally administered low molecular weight collagen\nhydrolysate in rats","volume":"58","author":"Watanabe-Kamiyama","year":"2010","journal-title":"J. Agric. Food Chem."},{"issue":"3","key":"2026092310083912700_cit23","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1248\/bpb.35.422","article-title":"Distribution\nof prolylhydroxyproline\nand its metabolites after oral administration in rats","volume":"35","author":"Kawaguchi","year":"2012","journal-title":"Biol. Pharm. Bull."},{"issue":"12","key":"2026092310083912700_cit24","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1080\/09168451.2015.1062711","article-title":"Absorption and plasma kinetics of collagen tripeptide after peroral\nor intraperitoneal administration in rats","volume":"79","author":"Yamamoto","year":"2015","journal-title":"Biosci.\nBiotechnol. Biochem."},{"issue":"11","key":"2026092310083912700_cit25","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1021\/acs.jafc.6b05679","article-title":"Oral ingestion\nof collagen hydrolysate\nleads to the transportation of highly concentrated Gly-Pro-Hyp and\nits hydrolyzed form of Pro-Hyp into the bloodstream and skin","volume":"65","author":"Yazaki","year":"2017","journal-title":"J. Agric. Food Chem."},{"issue":"14","key":"2026092310083912700_cit26","doi-asserted-by":"publisher","first-page":"2962","DOI":"10.1021\/acs.jafc.6b00609","article-title":"Efficient absorption\nof X-hydroxyproline (Hyp)-Gly after oral administration of a novel\ngelatin hydrolysate prepared using ginger protease","volume":"64","author":"Taga","year":"2016","journal-title":"J. Agric. Food Chem."},{"issue":"12","key":"2026092310083912700_cit27","doi-asserted-by":"publisher","first-page":"8427","DOI":"10.1021\/acs.analchem.0c01098","article-title":"Quantitative analysis\nof the positional\ndistribution of hydroxyproline in collagenous Gly-Xaa-Yaa sequences\nby LC-MS with partial acid hydrolysis and precolumn derivatization","volume":"92","author":"Taga","year":"2020","journal-title":"Anal. Chem."},{"issue":"50","key":"2026092310083912700_cit28","doi-asserted-by":"publisher","first-page":"12096","DOI":"10.1021\/jf5039597","article-title":"Highly accurate quantification\nof hydroxyproline-containing peptides in blood using a protease digest\nof stable isotope-labeled collagen","volume":"62","author":"Taga","year":"2014","journal-title":"J. Agric.\nFood Chem."},{"issue":"8","key":"2026092310083912700_cit29","doi-asserted-by":"publisher","first-page":"3671","DOI":"10.1021\/pr500213a","article-title":"Stable isotope-labeled\ncollagen: a novel and versatile tool for quantitative collagen analyses\nusing mass spectrometry","volume":"13","author":"Taga","year":"2014","journal-title":"J. Proteome Res."},{"issue":"16","key":"2026092310083912700_cit30","doi-asserted-by":"publisher","first-page":"4671","DOI":"10.1021\/acs.jafc.9b00571","article-title":"Improved in vivo tracking\nof orally administered collagen hydrolysate using stable isotope labeling\nand LC-MS techniques","volume":"67","author":"Taga","year":"2019","journal-title":"J. Agric. Food Chem."},{"issue":"3","key":"2026092310083912700_cit31","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/BF01062139","article-title":"Testing\nfor the equality of area under the curves when using destructive measurement\ntechniques","volume":"16","author":"Bailer","year":"1988","journal-title":"J. Pharmacokinet. Biopharm."},{"issue":"8","key":"2026092310083912700_cit32","doi-asserted-by":"publisher","first-page":"544","DOI":"10.2337\/diacare.12.8.544","article-title":"Effects\nof dose of ingested glucose on plasma metabolite and hormone responses\nin type II diabetic subjects","volume":"12","author":"Gannon","year":"1989","journal-title":"Diabetes Care"},{"issue":"4","key":"2026092310083912700_cit33","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1021\/bp030004i","article-title":"Production of tripeptide\nfrom gelatin using collagenase-immobilized\nporous hollow-fiber membrane","volume":"19","author":"Fujita","year":"2003","journal-title":"Biotechnol. Prog."},{"issue":"4","key":"2026092310083912700_cit34","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1074\/jbc.M109.068726","article-title":"Location of 3-hydroxyproline\nresidues in collagen types\nI, II, III, and V\/XI implies a role in fibril supramolecular assembly","volume":"285","author":"Weis","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"16","key":"2026092310083912700_cit35","doi-asserted-by":"publisher","first-page":"5987","DOI":"10.1074\/jbc.RA117.000406","article-title":"Post-translational\nmodification of type IV collagen with 3-hydroxyproline affects its\ninteractions with glycoprotein VI and nidogens 1 and 2","volume":"293","author":"Montgomery","year":"2018","journal-title":"J. Biol. Chem."},{"issue":"12","key":"2026092310083912700_cit36","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1038\/nchem.899","article-title":"Mineralization of the\nmetre-long biosilica structures of glass sponges is templated on hydroxylated\ncollagen","volume":"2","author":"Ehrlich","year":"2010","journal-title":"Nat. Chem."},{"issue":"10","key":"2026092310083912700_cit37","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1007\/s00726-021-03072-x","article-title":"The effects\nof collagen peptide supplementation on body composition, collagen\nsynthesis, and recovery from joint injury and exercise: a systematic\nreview","volume":"53","author":"Khatri","year":"2021","journal-title":"Amino Acids"},{"issue":"9","key":"2026092310083912700_cit38","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.3390\/nu15092080","article-title":"Effects of\noral collagen for skin\nanti-aging: A systematic review and meta-analysis","volume":"15","author":"Pu","year":"2023","journal-title":"Nutrients"},{"issue":"6","key":"2026092310083912700_cit39","doi-asserted-by":"publisher","first-page":"3008","DOI":"10.1039\/D3FO04949C","article-title":"Effects of collagen hydrolysates\non UV-induced photoaging mice: Gly-Pro-Hyp as a potent anti-photoaging\npeptide","volume":"15","author":"Yang","year":"2024","journal-title":"Food Funct."},{"key":"2026092310083912700_cit40","doi-asserted-by":"publisher","first-page":"116847","DOI":"10.1016\/j.foodres.2025.116847","article-title":"Production of collagen-derived hydroxyproline\n(Hyp)-containing di- and tripeptides by brush border membrane enzymes\nand their absorption characteristics","volume":"217","author":"Yang","year":"2025","journal-title":"Food Res.\nInt."},{"issue":"2","key":"2026092310083912700_cit41","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide\nfor dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"issue":"4","key":"2026092310083912700_cit42","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1021\/jf062834s","article-title":"Comparison\nof quantity and structures of hydroxyproline-containing peptides in\nhuman blood after oral ingestion of gelatin hydrolysates from different\nsources","volume":"55","author":"Ohara","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"2026092310083912700_cit43","doi-asserted-by":"publisher","first-page":"1416643","DOI":"10.3389\/fnut.2024.1416643","article-title":"Absorption\nof bioactive peptides\nfollowing collagen hydrolysate intake: a randomized, double-blind\ncrossover study in healthy individuals","volume":"11","author":"Virgilio","year":"2024","journal-title":"Front.\nNutr."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c08326","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/37\/29328\/68449542\/acs.jafc.6c08326.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/37\/29328\/68449542\/acs.jafc.6c08326.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:51:14Z","timestamp":1790175074000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/37\/29328\/5426423\/Oral-Ingestion-of-Jellyfish-Collagen-Hydrolysate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":43,"journal-issue":{"issue":"37","published-online":{"date-parts":[[2026,9,8]]},"published-print":{"date-parts":[[2026,9,23]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c08326","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]}}}