{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T18:46:11Z","timestamp":1782499571458,"version":"3.54.5"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017929","name":"Lion Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017929","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Oxidative stress, which can be triggered by various external stimuli, such as ultraviolet radiation and pollution, compromises skin health, accelerates aging and skin disorders, and impacts quality of life. This study investigated the potential of hydrolyzed corn starch containing maltotetraose in skin defense through nuclear factor erythroid 2-related factor 2 (NRF2) pathway activation in human keratinocytes. Using DNA microarray analysis and assessing key antioxidant-responsive genes, we evaluated the capacity of this ingredient to enhance cellular defense mechanisms. Human keratinocytes treated with it demonstrated significant upregulation of antioxidant-responsive genes, including\n                    <jats:italic>HMOX1<\/jats:italic>\n                    ,\n                    <jats:italic>GPX2<\/jats:italic>\n                    , and\n                    <jats:italic>NQO1<\/jats:italic>\n                    , which are known targets of NRF2. These findings were corroborated by western blotting and immunostaining analyses, which confirmed increased NRF2 protein expression and NRF2 nuclear translocation. Moreover, fluorescence assays and microscopy showed that treatment with the ingredient effectively reduced reactive oxygen species levels in keratinocytes exposed to oxidative stress. These results suggest that activation of the NRF2 pathway by this ingredient enhances the cellular antioxidative response and reduces reactive oxygen species levels in keratinocytes. This NRF2-mediated antioxidative activity positions hydrolyzed corn starch containing maltotetraose as a promising ingredient for cosmetic products, with potential implications for improving skin health, reducing pigmentation, and combating aging. However, these effects were not directly evaluated in this study. Future studies are warranted to evaluate its efficacy\n                    <jats:italic>in vivo.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0351422","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:48:55Z","timestamp":1782496135000},"page":"e0351422","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydrolyzed corn starch with maltotetraose for skin defense through NRF2 pathway activation in human keratinocytes"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5956-5820","authenticated-orcid":true,"given":"Hitomi","family":"Hagawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Otake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuko","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"issue":"1","key":"pone.0351422.ref001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.21315\/mjms2023.30.1.2","article-title":"Reactive oxygen species and antioxidant system in selected skin disorders","volume":"30","author":"J Md Jaffri","year":"2023","journal-title":"Malays J Med Sci"},{"issue":"12","key":"pone.0351422.ref002","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.3390\/antiox11122345","article-title":"Nrf2 and oxidative stress: a general overview of mechanisms and implications in human disease","volume":"11","author":"V Ngo","year":"2022","journal-title":"Antioxidants (Basel)"},{"issue":"1","key":"pone.0351422.ref003","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/biof.1907","article-title":"NRF2 in dermo-cosmetic: From scientific knowledge to skin care products","volume":"49","author":"M-C Frantz","year":"2023","journal-title":"Biofactors"},{"issue":"5","key":"pone.0351422.ref004","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1111\/ics.12728","article-title":"Oxidative stress in the skin: Impact and related protection","volume":"43","author":"J Chen","year":"2021","journal-title":"Int J Cosmet Sci"},{"key":"pone.0351422.ref005","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.freeradbiomed.2015.04.018","article-title":"Nrf2--A regulator of keratinocyte redox signaling","volume":"88","author":"M Sch\u00e4fer","year":"2015","journal-title":"Free Radic Biol Med"},{"issue":"2","key":"pone.0351422.ref006","doi-asserted-by":"crossref","DOI":"10.1002\/biof.70013","article-title":"The role of NRF2 transcription factor in inflammatory skin diseases","volume":"51","author":"S Salman","year":"2025","journal-title":"Biofactors"},{"issue":"1","key":"pone.0351422.ref007","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3390\/antiox15010069","article-title":"Emerging therapeutic strategies for Nrf2-associated skin disorders: from photoaging to autoimmunity","volume":"15","author":"HJ Kim","year":"2026","journal-title":"Antioxidants (Basel)"},{"key":"pone.0351422.ref008","doi-asserted-by":"crossref","DOI":"10.1177\/1091581811403832","article-title":"Final report of the safety assessment of cosmetic ingredients derived from Zea mays (corn)","volume":"30","author":"FA Andersen","year":"2011","journal-title":"Int J Toxicol"},{"key":"pone.0351422.ref009","doi-asserted-by":"crossref","first-page":"100015","DOI":"10.1016\/j.jdsct.2024.100015","article-title":"Sensitive skin syndrome: Research progress on mechanisms and applications","volume":"1","author":"C Jiang","year":"2024","journal-title":"J Dermatol Sci Cosmet Technol"},{"issue":"5","key":"pone.0351422.ref010","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/bjd.18025","article-title":"Substance P and neurokinin 1 receptor are new targets for the treatment of chronic pruritus","volume":"181","author":"S St\u00e4nder","year":"2019","journal-title":"Br J Dermatol"},{"issue":"6","key":"pone.0351422.ref011","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s40265-021-01478-1","article-title":"Neurokinin 1 receptor antagonists for pruritus","volume":"81","author":"M Alam","year":"2021","journal-title":"Drugs"},{"key":"pone.0351422.ref012","volume-title":"NK1 receptor antagonist composition","author":"T Uozumi","year":"2013"},{"issue":"3","key":"pone.0351422.ref013","first-page":"187","article-title":"Clinical evaluation of the efficacy of Itch-Relief moisturizers containing maltotetraose for dry, itchy, and sensitive skin","volume":"22","author":"E Ichikawa","year":"2024","journal-title":"Skinmed"},{"issue":"4792","key":"pone.0351422.ref014","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1126\/science.3029864","article-title":"Bilirubin is an antioxidant of possible physiological importance","volume":"235","author":"R Stocker","year":"1987","journal-title":"Science"},{"key":"pone.0351422.ref015","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev.pharmtox.46.120604.141046","article-title":"Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway","volume":"47","author":"TW Kensler","year":"2007","journal-title":"Annu Rev Pharmacol Toxicol"},{"issue":"6563","key":"pone.0351422.ref016","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/379335a0","article-title":"Molecular basis of sun-induced premature skin ageing and retinoid antagonism","volume":"379","author":"GJ Fisher","year":"1996","journal-title":"Nature"},{"issue":"6","key":"pone.0351422.ref017","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1172\/JCI2153","article-title":"Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo","volume":"101","author":"GJ Fisher","year":"1998","journal-title":"J Clin Invest"},{"issue":"34","key":"pone.0351422.ref018","doi-asserted-by":"crossref","first-page":"24675","DOI":"10.1016\/S0021-9258(18)35817-4","article-title":"Endothelins secreted from human keratinocytes are intrinsic mitogens for human melanocytes","volume":"267","author":"G Imokawa","year":"1992","journal-title":"J Biol Chem"},{"issue":"10","key":"pone.0351422.ref019","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s00403-016-1692-1","article-title":"Low-concentration hydrogen peroxide can upregulate keratinocyte intracellular calcium and PAR-2 expression in a human keratinocyte-melanocyte co-culture system","volume":"308","author":"J Li","year":"2016","journal-title":"Arch Dermatol Res"},{"issue":"13","key":"pone.0351422.ref020","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.3390\/ijms21134777","article-title":"NRF2, a Transcription Factor for Stress Response and Beyond","volume":"21","author":"F He","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"10","key":"pone.0351422.ref021","doi-asserted-by":"crossref","first-page":"7266","DOI":"10.3390\/molecules15107266","article-title":"The Nrf2 system as a potential target for the development of indirect antioxidants","volume":"15","author":"K-A Jung","year":"2010","journal-title":"Molecules"},{"key":"pone.0351422.ref022","doi-asserted-by":"crossref","first-page":"11624","DOI":"10.1038\/ncomms11624","article-title":"Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription","volume":"7","author":"EH Kobayashi","year":"2016","journal-title":"Nat Commun"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0351422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:49:00Z","timestamp":1782496140000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0351422"}},"subtitle":[],"editor":[{"given":"Ahmed E.","family":"Abdel Moneim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":22,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0351422","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]}}}