{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:08:08Z","timestamp":1779167288090,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>\u201cSupersulfides\u201d is a general term for compounds containing multiple sulfur atoms within their molecules. Owing to their potent anti-oxidant and anti-inflammatory activities, these species are promising ingredients in the field of cosmetics. In this study, we elucidated the effect of silver tip (Camellia sinensis) tea on supersulfide production in epidermal keratinocytes. Silver tip extract increased the fluorescence intensity of sulfane sulfur probe 4 (SSP4) in a concentration-dependent manner and promoted supersulfide production in keratinocytes. In particular, (\u2212)-epicatechin gallate and (\u2212)-epigallocatechin gallate exhibited high SSP4 fluorescence intensity, indicating that these are the active components. Mechanistic analysis using quantitative polymerase chain reaction revealed that silver tip extract promotes intracellular supersulfide production by regulating supersulfide-related metabolic factors (cysteinyl-tRNA synthetase 2, cystathionine \u03b2-synthase, cystathionine \u03b3-lyase, solute carrier family 7 member 11, and nuclear factor E2-related factor 2). Furthermore, these compounds significantly increased the supersulfide levels by reacting with sodium sulfide, a hydrogen sulfide donor, in buffer solution, thereby catalytically enhancing supersulfide production. Overall, the results of this study indicate that silver tip extract, rich in polyphenols, regulates supersulfide metabolism in keratinocytes, suggesting its potential as an anti-aging ingredient for the skin.<\/jats:p>","DOI":"10.3390\/ijms27104214","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Silver Tip (Camellia sinensis) Extract Promotes Supersulfide Biosynthesis in Keratinocytes"],"prefix":"10.3390","volume":"27","author":[{"given":"Kento","family":"Kunihiro","sequence":"first","affiliation":[{"name":"ALBION Co., Ltd., 1-7-10 Ginza, Chuo-ku, Tokyo 104-0061, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsura","family":"Sano","sequence":"additional","affiliation":[{"name":"ALBION Co., Ltd., 1-7-10 Ginza, Chuo-ku, Tokyo 104-0061, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shogo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"ALBION Co., Ltd., 1-7-10 Ginza, Chuo-ku, Tokyo 104-0061, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eadg8631","DOI":"10.1126\/sciadv.adg8631","article-title":"Supersulfide catalysis for nitric oxide and aldehyde metabolism","volume":"9","author":"Kasamatsu","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1038\/s41467-023-40182-4","article-title":"Supersulphides provide airway protection in viral and chronic lung diseases","volume":"14","author":"Matsunaga","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/bph.16271","article-title":"Supersulfide biology and translational medicine for disease control","volume":"183","author":"Barayeu","year":"2023","journal-title":"Br. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1038\/s41467-017-01311-y","article-title":"Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics","volume":"8","author":"Akaike","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7606","DOI":"10.1073\/pnas.1321232111","article-title":"Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling","volume":"111","author":"Ida","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10459","DOI":"10.1038\/s41598-017-11004-7","article-title":"3-mercaptopyruvate sulfurtransferase produces potential redox regulators cysteine- and glutathione-persulfide (Cys-SSH and GSSH) together with signaling molecules H2S2, H2S3 and H2S","volume":"7","author":"Kimura","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102624","DOI":"10.1016\/j.redox.2023.102624","article-title":"Contribution of NRF2 to sulfur metabolism and mitochondrial activity","volume":"60","author":"Alam","year":"2023","journal-title":"Redox Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1089\/ars.2020.8073","article-title":"High-precision sulfur metabolomics innovated by a new specific probe for trapping reactive sulfur species","volume":"34","author":"Kasamatsu","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101096","DOI":"10.1016\/j.redox.2019.101096","article-title":"Polysulfide stabilization by tyrosine and hydroxyphenyl-containing derivatives that is important for a reactive sulfur metabolomics analysis","volume":"21","author":"Hamid","year":"2019","journal-title":"Redox Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"135610","DOI":"10.1016\/j.foodchem.2023.135610","article-title":"Development of methods for quantitative determination of total and reactive polysulfides: Reactive polysulfide profiling in vegetables","volume":"413","author":"Kasamatsu","year":"2023","journal-title":"Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1080\/09273948.2020.1833224","article-title":"Glutathione trisulfide prevents lipopolysaccharide-induced inflammatory gene expression in retinal pigment epithelial cells","volume":"30","author":"Tawarayama","year":"2022","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11513","DOI":"10.1038\/s41598-023-38696-4","article-title":"Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells","volume":"13","author":"Tawarayama","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102620","DOI":"10.1016\/j.redox.2023.102620","article-title":"Intranasal administration of polysulfide prevents neurodegeneration in spinal cord and rescues mice from delayed paraplegia after spinal cord ischemia","volume":"60","author":"Kanemaru","year":"2023","journal-title":"Redox Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102605","DOI":"10.1016\/j.redox.2023.102605","article-title":"Cysteine hydropersulfide reduces lipid peroxidation and protects against myocardial ischaemia-reperfusion injury\u2014Are endogenous persulfides mediators of ischaemic preconditioning?","volume":"60","author":"Griffiths","year":"2023","journal-title":"Redox Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.chembiol.2019.02.003","article-title":"Enhanced cellular polysulfides regulate TLR4 signaling and mitigate endotoxin shock","volume":"26","author":"Zhang","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1080\/10715762.2023.2165918","article-title":"Antioxidant action of persulfides against lipid peroxidation","volume":"56","author":"Kaneko","year":"2022","journal-title":"Free Radic. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103018","DOI":"10.1016\/j.redox.2023.103018","article-title":"Longevity control by supersulfide-mediated mitochondrial respiration and regulation of protein quality","volume":"69","author":"Nishimura","year":"2024","journal-title":"Redox Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ikeda, M., Ishima, Y., Chuang, V.T.G., Sakai, M., Osafune, H., Ando, H., Shimizu, T., Okuhira, K., Watanabe, H., and Maruyama, T. (2019). Distribution of polysulfide in human biological fluids and association with amylase and sperm activities. Molecules, 24.","DOI":"10.3390\/molecules24091689"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100091","DOI":"10.1016\/j.arres.2023.100091","article-title":"Human hair keratin responds to oxidative stress via reactive sulfur and supersulfides","volume":"10","author":"Hirai","year":"2024","journal-title":"Adv. Redox Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1247\/csf.25018","article-title":"Supersulfides regulate cell migration in human skin keratinocytes","volume":"50","author":"Kunihiro","year":"2025","journal-title":"Cell Struct. Funct."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1111\/1541-4337.12479","article-title":"Chemistry and biological activities of processed Camellia sinensis teas: A comprehensive review","volume":"18","author":"Zhang","year":"2019","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.biosystemseng.2013.08.002","article-title":"Nondestructive grading of black tea based on physical parameters by texture analysis","volume":"116","author":"Gill","year":"2013","journal-title":"Biosyst. Eng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.foodres.2013.01.025","article-title":"Human exposure assessment of fluoride from tea (Camellia sinensis L.): A UK-based issue?","volume":"51","author":"Chan","year":"2013","journal-title":"Food Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104473","DOI":"10.1016\/j.jfca.2022.104473","article-title":"Identification of discriminatory chemical markers of different grades of Sri Lankan white, green and black tea (Camellia sinenesis L.) via metabolomics combined to chemometrics","volume":"109","author":"Selim","year":"2022","journal-title":"J. Food Compos. Anal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biosystemseng.2021.12.023","article-title":"An adaptive fuzzy logic control of green tea fixation process based on image processing technology","volume":"215","author":"Chen","year":"2022","journal-title":"Biosyst. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1080\/10408398.2014.1003365","article-title":"Molecular mechanisms of green tea polyphenols against skin photoaging","volume":"57","author":"Roh","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_27","first-page":"42","article-title":"The relationship between using green tea in preventing skin aging: A literature review","volume":"14","author":"Pebrianti","year":"2025","journal-title":"J. Kesehat. JKes"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Prasanth, M.I., Sivamaruthi, B.S., Chaiyasut, C., and Tencomnao, T. (2019). Role of green tea in antiphotoaging, stress resistance, neuroprotection, and autophagy. Nutrients, 11.","DOI":"10.3390\/nu11020474"},{"key":"ref_29","first-page":"1307","article-title":"Green tea polyphenolic antioxidants and skin photoprotection","volume":"18","author":"Katiyar","year":"2001","journal-title":"Int. J. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sun, M.-F., Jiang, C.-L., Kong, Y.-S., Luo, J.-L., Yin, P., and Guo, G.-Y. (2022). Advances in analytical methods for determination of polyphenols in tea: A comprehensive review. Foods, 11.","DOI":"10.3390\/foods11101425"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1126\/science.abo0693","article-title":"Microbiota and maintenance of skin barrier function","volume":"376","author":"Grice","year":"2022","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.freeradbiomed.2021.01.035","article-title":"\u2018Antioxidant\u2019 berries, anthocyanins, resveratrol and rosmarinic acid oxidize hydrogen sulfide to polysulfides and thiosulfate: A novel mechanism underlying their biological actions","volume":"165","author":"Olson","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101731","DOI":"10.1016\/j.redox.2020.101731","article-title":"Green tea polyphenols oxidize hydrogen sulfide to thiosulfate and polysulfides: A possible new mechanism underpinning their biological action","volume":"37","author":"Olson","year":"2020","journal-title":"Redox Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8198","DOI":"10.12659\/MSM.911175","article-title":"Epigallocatechin gallate as an effective catechin against oxidative stress","volume":"24","author":"He","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.abb.2008.03.002","article-title":"Impact of the 67 kDa laminin receptor on binding and anti-allergic action of tea catechins","volume":"476","author":"Fujimura","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.3136\/fstr.20.1245","article-title":"Tea catechins inhibit cell proliferation through hydrogen peroxide- dependent and -independent pathways in human T lymphocytic leukemia jurkat cells","volume":"20","author":"Tang","year":"2014","journal-title":"Food Sci. Technol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bechelli, C., Macabrey, D., Deglise, S., and Allagnat, F. (2023). Clinical potential of hydrogen sulfide in peripheral arterial disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24129955"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.redox.2015.03.003","article-title":"Expression of xCT and activity of system xc- are regulated by NRF2 in human breast cancer cells in response to oxidative stress","volume":"5","author":"Habib","year":"2015","journal-title":"Redox Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102834","DOI":"10.1016\/j.redox.2023.102834","article-title":"Sulfur metabolic response in macrophages limits inflammatory response","volume":"65","author":"Takeda","year":"2023","journal-title":"Redox Biol."},{"key":"ref_40","first-page":"412","article-title":"Cadmium-mediated activation of the HSP90\/HSF1 pathway regulated by persulfides","volume":"156","author":"Shinkai","year":"2017","journal-title":"Toxicol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1089\/ars.2012.4944","article-title":"The Gasotransmitter Hydrogen Sulfide Induces Nrf2-Target Genes by Inactivating the Keap1 Ubiquitin Ligase Substrate Adaptor through Formation of a Disulfide Bond between Cys-226 and Cys-613","volume":"19","author":"Hourihan","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Koch, W., Zag\u00f3rska, J., Marzec, Z., and Kukula-Koch, W. (2019). Applications of Tea (Camellia sinensis) and Its Active Constituents in Cosmetics. Molecules, 24.","DOI":"10.3390\/molecules24234277"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3109\/10837450.2013.788512","article-title":"Effect of emulsification on the skin permeation and UV protection of catechin","volume":"19","author":"Yoashino","year":"2014","journal-title":"Pharm. Dev. Technol."},{"key":"ref_44","first-page":"175","article-title":"Antiglycative effect of extract and phenolic compounds from Holy Basil (Ocimum tenuiflorum)","volume":"9","author":"Kunihiro","year":"2022","journal-title":"Glycative Stress Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:17:23Z","timestamp":1779164243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,9]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104214"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104214","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,9]]}}}