{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:07:12Z","timestamp":1790644032901,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hyperpigmentation and pigmentary disorders are major clinical consequences of sun exposure. While UV radiation is a known contributor, visible light (VL), particularly High Energy Visible (HEV) light (400\u2013450\u00a0nm), also induces long-lasting pigmentation in melanocompetent individuals (Fitzpatrick Phototype III and above), and can worsen pigmentary disorders. Therefore, photoprotection in this wavelengths range is recommended to prevent worsening of hyperpigmentation issues. Efficient solutions rely on the use of pigments, absorbing and diffusing VL. However, tint and opacity of these products may limit their use by consumers and patients. The search for actives preventing VL-induced pigmentation is therefore of interest. This work aimed at assessing 2 non tinted biological actives to counteract HEV-induced pigmentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Two very potent inhibitors of UV-induced pigmentation, ascorbic acid 7% (powerful antioxidant) and 2-mercaptonicotinoyl glycine (2-MNG, 0.5 or 1%, melanogenesis inhibitor), were assessed in 2 controlled randomized clinical trials (registered under the identification numbers NCT06945393 and NCT06937515 on <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>), including in total, 58 individuals with Fitzpatrick Phototype III or IV. Delineated areas on the subjects back, topically treated or not by the product, were exposed to HEV once a day for 4 days. The product was applied before, during and 5 weeks after HEV exposure. Pigmentation was assessed using chromametry and visual scoring throughout the studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While ascorbic acid did not exhibit any efficacy versus its vehicle in limiting skin hyperpigmentation induced by HEV, the use of 2-MNG (0.5 or 1%) led to an early significant decrease in HEV-induced pigmentation, which was sustained until the end of the study, as evidenced by colorimetry and significantly scored by visual assessment. Moreover, a 2-MNG dose effect could be evidenced at early time points.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>2-MNG represents an efficient and transparent alternative solution to pigments for the mitigation of HEV worsening of hyperpigmentation issues. This opens up perspectives for its use as a complement to UV protection afforded by sun filters.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1651068","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T05:28:43Z","timestamp":1759987723000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Topical prevention from high energy visible light-induced pigmentation by 2-mercaptonicotinoyl glycine, but not by ascorbic acid antioxidant: 2 randomized controlled trials"],"prefix":"10.3389","volume":"16","author":[{"given":"Virginie","family":"Piffaut","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"De Dormael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Belaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laudine","family":"Bertrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Passeron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Bernerd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Marionnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"B1","first-page":"14","article-title":"Topical vitamin C and the skin: mechanisms of action and clinical applications","volume":"10","author":"Al-Niaimi","year":"2017","journal-title":"J. Clin. Aesthet. Dermatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/sj.jid.5700683","article-title":"Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase","volume":"127","author":"Ando","year":"2007","journal-title":"J. Invest. Dermatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.cell.2006.12.045","article-title":"Central role of p53 in the suntan response and pathologic hyperpigmentation","volume":"128","author":"Cui","year":"2007","journal-title":"Cell"},{"key":"B4","first-page":"E53","article-title":"Vitamin C prevents ultraviolet-induced pigmentation in healthy volunteers: bayesian meta-analysis results from 31 randomized controlled versus vehicle clinical studies","volume":"12","author":"De Dormael","year":"2019","journal-title":"J. Clin. Aesthet. Dermatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1111\/jocd.15651","article-title":"Gain of photoprotection afforded by the cyclic merocyanine UVA1 absorber MCE\u00ae in sunscreen formulae: a dose effect in vivo clinical trial","volume":"22","author":"de Dormael","year":"2023","journal-title":"J. Cosmet. Dermatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1111\/jocd.16200","article-title":"2-Mercaptonicotinoyl glycine prevents UV-induced skin darkening and delayed tanning in healthy subjects: a randomized controlled clinical study","volume":"23","author":"de Dormael","year":"2024","journal-title":"J. Cosmet. Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"198","DOI":"10.12788\/cutis.0504","article-title":"Tinted sunscreens: consumer preferences based on light, medium, and dark skin tones","volume":"109","author":"De La Garza","year":"2022","journal-title":"Cutis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1111\/pcmr.12273","article-title":"Differences in visible light-induced pigmentation according to wavelengths: a clinical and histological study in comparison with UVB exposure","volume":"27","author":"Duteil","year":"2014","journal-title":"Pigment. Cell Melanoma Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1111\/phpp.12325","article-title":"A method to assess the protective efficacy of sunscreens against visible light-induced pigmentation","volume":"33","author":"Duteil","year":"2017","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"B10","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/jdv.18034","article-title":"A new in vitro method to predict in vivo photoprotection of skin hyperpigmentation induced by visible light","volume":"36","author":"Duteil","year":"2022","journal-title":"J. Eur. Acad. Dermatol Venereol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/s0190-9622(96)90830-0","article-title":"Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo","volume":"34","author":"Kameyama","year":"1996","journal-title":"J. Am. Acad. Dermatol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1111\/j.1751-1097.1984.tb03905.x","article-title":"An experimental study of the changes in pigmentation in human skin in vivo with visible and near infrared light","volume":"39","author":"Kollias","year":"1984","journal-title":"Photochem Photobiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/j.1600-0781.1999.tb00080.x","article-title":"Immediate pigment darkening thresholds of human skin to monochromatic (362 nm) ultraviolet A radiation are fluence rate dependent","volume":"15","author":"Kollias","year":"1999","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"B14","doi-asserted-by":"publisher","first-page":"345","DOI":"10.3177\/jnsv.44.345","article-title":"In vitro and in vivo prolonged biological activities of novel vitamin C derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), in cosmetic fields","volume":"44","author":"Kumano","year":"1998","journal-title":"J. Nutr. Sci. Vitaminol. (Tokyo)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"12722","DOI":"10.1038\/s41598-018-30738-6","article-title":"The UV\/Visible radiation boundary region (385-405 nm) damages skin cells and induces \u201cdark\u201d cyclobutane pyrimidine dimers in human skin in vivo","volume":"8","author":"Lawrence","year":"2018","journal-title":"Sci. Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1038\/jid.2011.476","article-title":"Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes","volume":"132","author":"Liebel","year":"2012","journal-title":"J. Invest. Dermatol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/j.jaad.2020.04.079","article-title":"Photoprotection beyond ultraviolet radiation: a review of tinted sunscreens","volume":"84","author":"Lyons","year":"2021","journal-title":"J. Am. Acad. Dermatol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/php.13525","article-title":"Mitigating visible light and long wavelength UVA1-induced effects with topical antioxidants","volume":"98","author":"Lyons","year":"2022","journal-title":"Photochem Photobiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1038\/jid.2010.95","article-title":"Impact of long-wavelength UVA and visible light on melanocompetent skin","volume":"130","author":"Mahmoud","year":"2010","journal-title":"J. Invest. Dermatol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1111\/phpp.12523","article-title":"High-energy visible light at ambient doses and intensities induces oxidative stress of skin-protective effects of the antioxidant and Nrf2 inducer Licochalcone A in vitro and in vivo","volume":"36","author":"Mann","year":"2020","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/j.jid.2016.12.016","article-title":"UVA1-Induced skin darkening is associated with molecular changes Even in highly pigmented skin individuals","volume":"137","author":"Marionnet","year":"2017","journal-title":"J. Invest. Dermatol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/jdv.18948","article-title":"A precise analysis of the relative contribution of UVA1 and visible light colour domains in solar light-induced skin pigmentation","volume":"37","author":"Marionnet","year":"2023","journal-title":"J. Eur. Acad. Dermatol Venereol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1111\/jdv.19910","article-title":"A Bayesian network meta-analysis of 14 molecules inhibiting UV daylight-induced pigmentation","volume":"38","author":"Muller","year":"2024","journal-title":"J. Eur. Acad. Dermatol Venereol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.freeradbiomed.2020.07.013","article-title":"Ascorbic acid: the chemistry underlying its antioxidant properties","volume":"159","author":"Njus","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jdermsci.2006.07.001","article-title":"A new lipophilic pro-vitamin C, tetra-isopalmitoyl ascorbic acid (VC-IP), prevents UV-induced skin pigmentation through its anti-oxidative properties","volume":"44","author":"Ochiai","year":"2006","journal-title":"J. Dermatol Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.jphotobiol.2011.02.018","article-title":"Effects of blue light irradiation on human dermal fibroblasts","volume":"103","author":"Opl\u00e4nder","year":"2011","journal-title":"J. Photochem Photobiol. B"},{"key":"B27","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/jdv.16614","article-title":"Clinical and biological impact of the exposome on the skin","volume":"34","author":"Passeron","year":"2020","journal-title":"J. Eur. Acad. Dermatol Venereol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1111\/jdv.17242","article-title":"Photoprotection according to skin phototype and dermatoses: practical recommendations from an expert panel","volume":"35","author":"Passeron","year":"2021","journal-title":"J. Eur. Acad. Dermatol Venereol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/jid.1962.136","article-title":"Melanogenesis in human skin following exposure to long-wave ultraviolet and visible light**from the research laboratories of the department of dermatology of the harvard medical school at the Massachusetts General Hospital, Boston 14, Massachusetts","volume":"39","author":"Pathak","year":"1962","journal-title":"J. Invest. Dermatol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1039\/c1pp05202k","article-title":"Are there mechanistic differences between ultraviolet and visible radiation induced skin pigmentation?","volume":"10","author":"Ramasubramaniam","year":"2011","journal-title":"Photochem Photobiol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s00403-006-0728-3","article-title":"Pigmentation after single and multiple UV-exposures depending on UV-spectrum","volume":"299","author":"Ravnbak","year":"2007","journal-title":"Arch. Dermatol Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"357","DOI":"10.2340\/00015555-0635","article-title":"Skin pigmentation kinetics after exposure to ultraviolet A","volume":"89","author":"Ravnbak","year":"2009","journal-title":"Acta Derm. Venereol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.jid.2017.07.833","article-title":"Melanocytes sense blue light and regulate pigmentation through Opsin-3","volume":"138","author":"Regazzetti","year":"2018","journal-title":"J. Invest. Dermatol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e70167","DOI":"10.1111\/exd.70167","article-title":"Visible light-induced pigmentation: improved in\u00a0Vivo Metvivology formMeasuring Effmcacy of e0 Products in p Randomised Conrrolled Tricls andtCorrelation Witc In\u00a0witro Assessinnt","volume":"34","author":"Renoux","year":"2025","journal-title":"Exp. Dermatol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1111\/j.1751-1097.1990.tb01969.x","article-title":"Immediate pigment darkening: visual and reflectance spectrophotometric analysis of action spectrum","volume":"51","author":"Rosen","year":"1990","journal-title":"Photochem Photobiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/ics.12785","article-title":"Evaluation of efficacy of antioxidant-enriched sunscreen prodcuts against long wavelength ultraviolet A1 and visible light","volume":"44","author":"Ruvolo","year":"2022","journal-title":"Int. J. Cosmet. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1111\/pcmr.13168","article-title":"2-Mercaptonicotinoyl glycine, a new potent melanogenesis inhibitor, exhibits a unique mode of action while preserving melanocyte integrity","volume":"37","author":"Sextius","year":"2024","journal-title":"Pigment. Cell Melanoma Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1039\/c2pp25152c","article-title":"Effects of ultraviolet radiation, visible light, and infrared radiation on erythema and pigmentation: a review","volume":"12","author":"Sklar","year":"2013","journal-title":"Photochem Photobiol. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.jaad.2022.01.051","article-title":"Disorders of hyperpigmentation. Part I. Pathogenesis and clinical features of common pigmentary disorders","volume":"88","author":"Wang","year":"2023","journal-title":"J. Am. Acad. Dermatol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/j.jid.2024.07.034","article-title":"The Pigmentation of Blue Light Is Mediated by Both Melanogenesis Activation and Autophagy Inhibition through OPN3-TRPV1","volume":"145","author":"Yu","year":"2025","journal-title":"J. Invest. Dermatol"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1651068\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T05:28:45Z","timestamp":1759987725000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1651068\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":40,"alternative-id":["10.3389\/fphar.2025.1651068"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1651068","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]},"article-number":"1651068"}}