{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T07:18:03Z","timestamp":1765178283935,"version":"3.46.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Melanin, a pigment synthesized by melanocytes, serves as the primary defense against UV-induced skin damage due to its potent antioxidant properties. There is increasing interest in natural substances capable of modulating the melanogenic pathway, particularly in hypopigmentation disorders. This study investigated the effect of methanolic extracts from the diatom Odontella aurita\u2014authorized as a food supplement in the EU\u2014on melanogenesis in the B16-F0 murine melanoma cell line. The research evaluated melanin content, tyrosinase activity, and the expression of melanogenesis-related genes and proteins at defined time points. Metabolomic and biochemical analyses were performed to characterize the extract\u2019s composition. Treatment with O. aurita extract significantly increased melanin content in B16-F0 cells by 45% (p &lt; 0.01) compared to control. Tyrosinase activity was elevated by 38% after 24 h (p &lt; 0.01), with gene and protein expression analyses confirming upregulation of Tyrosinase (TYR) after 0.5 h, Tyrosinase Related Protein-1 (TRP1) after 1 h, and Tyrosinase Related Protein-2 (TRP2) after 8 h. The extract also enhanced the cellular antioxidant environment, as evidenced by increased levels of metabolic cofactors and pigment-precursor amino acids. O. aurita methanolic extract accelerates and sustains melanin synthesis and tyrosinase activity, distinguishing its effect from single-compound inducers. These findings support the therapeutic potential of O. aurita for pigmentary disorders and skin health. Further studies should investigate its efficacy and safety in vivo and explore its application in cosmeceutical and nutraceutical formulations.<\/jats:p>","DOI":"10.3390\/antiox14121402","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T15:29:47Z","timestamp":1764084587000},"page":"1402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Diatom Odontella aurita Modulates Melanogenesis in B16-F0 Cell Line"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-8154","authenticated-orcid":false,"given":"Clementina","family":"Sansone","sequence":"first","affiliation":[{"name":"Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2638-2935","authenticated-orcid":false,"given":"Luigi","family":"Pistelli","sequence":"additional","affiliation":[{"name":"Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4526-8353","authenticated-orcid":false,"given":"Debora","family":"Paris","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry, National Research Council, 80078 Pozzuoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2425-2670","authenticated-orcid":false,"given":"Annabella","family":"Tramice","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry, National Research Council, 80078 Pozzuoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7283-2152","authenticated-orcid":false,"given":"Annalaura","family":"Iodice","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry, National Research Council, 80078 Pozzuoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1435-358X","authenticated-orcid":false,"given":"Christophe","family":"Brunet","sequence":"additional","affiliation":[{"name":"Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.abb.2014.06.030","article-title":"The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1\u03b1 expression and HIF-dependent attendant pathways","volume":"563","author":"Slominski","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1111\/febs.16613","article-title":"The UV-induced uptake of melanosome by skin keratinocyte is triggered by \u03b17 nicotinic acetylcholine receptor-mediated phagocytosis","volume":"290","author":"Guo","year":"2023","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1039\/D2AN00588C","article-title":"Inhibition mechanism of melanin formation based on antioxidant scavenging of reactive oxygen species","volume":"147","author":"Fu","year":"2022","journal-title":"Analyst"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119915","DOI":"10.1016\/j.lfs.2021.119915","article-title":"The relationship between melanin production and lipofuscin formation in Tyrosinase gene knockout melanocytes using CRISPR\/Cas9 system","volume":"284","author":"Kim","year":"2021","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1159\/000506103","article-title":"Vitiligo: A Review","volume":"236","author":"Bergqvist","year":"2020","journal-title":"Dermatology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chang, W.L., and Ko, C.H. (2023). The Role of Oxidative Stress in Vitiligo: An Update on Its Pathogenesis and Therapeutic Implications. Cells, 12.","DOI":"10.3390\/cells12060936"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1177\/0009922817734362","article-title":"Serum 25-hydroxyvitamin D status in chinese children with vitiligo: A case-control study","volume":"57","author":"Zhang","year":"2018","journal-title":"Clin. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e460","DOI":"10.1002\/ski2.460","article-title":"Vitiligo: From mechanisms of disease to treatable pathways","volume":"4","author":"Pathak","year":"2024","journal-title":"Skin. Health Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.det.2016.11.012","article-title":"The Role of Diet and Supplements in Vitiligo Management","volume":"35","author":"Grimes","year":"2017","journal-title":"Dermatol. Clin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1002\/ptr.5161","article-title":"The effects of galangin on a mouse model of vitiligo induced by hydroquinone","volume":"28","author":"Huo","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/med.21754","article-title":"Mechanisms of melanocyte death in vitiligo","volume":"41","author":"Chen","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.foodchem.2016.10.140","article-title":"Novel inhibitors of tyrosinase produced by the 4-substitution of TCT","volume":"221","author":"Xu","year":"2017","journal-title":"Food Chem."},{"key":"ref_13","first-page":"1039","article-title":"New insights in vitiligo treatments using bioactive compounds from Piper nigrum","volume":"17","author":"Tatu","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sansone, C., Bruno, A., Piscitelli, C., Baci, D., Fontana, A., Brunet, C., Noonan, D.M., and Albini, A. (2021). Natural Compounds of Marine Origin as Inducers of Immunogenic Cell Death (ICD): Potential Role for Cancer Interception and Therapy. Cells, 10.","DOI":"10.3390\/cells10020231"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1080\/14756366.2021.1960830","article-title":"Cyanobacteria and microalgae bioactive compounds in skin-ageing: Potential to restore extracellular matrix filling and overcome hyperpigmentation","volume":"36","author":"Favas","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sharma, N., Simon, D.P., Diaza-Garza, A.M., Fantino, E., Messaabi, A., Meddeb-Mouelhi, F., Germain, H., and Desgagn\u00e9-Penix, I. (2021). Diatoms Biotechnology: Various Industrial Applications for a Greener Tomorrow. Front. Mar. Sci., 8.","DOI":"10.3389\/fmars.2021.636613"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Goessling, J.W., Ser\u00f4dio, J., and Lavaud, J. (2024). Opportunities and Challenges of Diatom Cell Factory for Human Health. Diatom Photosynthesis: From Primary Production to High-Value Molecules, Scrivener Publishing LLC.","DOI":"10.1002\/9781119842156"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Guler, B.A., Deniz, I., Demirel, Z., Yesil-Celiktas, O., and Imamoglu, E. (2020). A novel subcritical fucoxanthin extraction with a biorefinery approach. Biochem. Eng. J., 153.","DOI":"10.1016\/j.bej.2019.107403"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sansone, C., Pistelli, L., Del Mondo, A., Calabrone, L., Fontana, A., Noonan, D.M., Albini, A., and Brunet, C. (2023). The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells. Antioxidants, 11.","DOI":"10.3390\/antiox11081515"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sansone, C., Pistelli, L., Calabrone, L., Del Mondo, A., Fontana, A., Festa, M., Noonan, D.M., Albini, A., and Brunet, C. (2023). The Carotenoid Diatoxanthin Modulates Inflammatory and Angiogenesis Pathways In vitro in Prostate Cancer Cells. Antioxidants, 12.","DOI":"10.3390\/antiox12020359"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sansone, C., Pistelli, L., and Brunet, C. (2025). The marine xanthophyll diatoxanthin as ferroptosis inducer in MDAMB231 breast cancer cells. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-91519-6"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Singh, M., Mal, N., Trivedi, D., Krishnamoorthy, S., Behera, C., Krishnan, C., Naik, S., and Kuppa, C. (2024). An overview of the role of algae-fortified foods in nutraceutical industries: Synthesis pathway of value-added bioproducts and co-products. Food Biosci., 63.","DOI":"10.1016\/j.fbio.2024.105568"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.3390\/md11072667","article-title":"Production, characterization, and antioxidant activity of fucoxanthin from the marine diatom Odontella aurita","volume":"11","author":"Xia","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jbiosc.2018.06.002","article-title":"Production of fucoxanthin, chrysolaminarin, and eicosapentaenoic acid by Odontella aurita under different nitrogen supply regimes","volume":"126","author":"Xia","year":"2018","journal-title":"J. Biosci. Bioeng."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Merecz-Sadowska, A., Sitarek, P., Kowalczyk, T., Zajdel, K., Kucharska, E., and Zajdel, R. (2022). The Modulation of Melanogenesis in B16 Cells Upon Treatment with Plant Extracts and Isolated Plant Compounds. Molecules, 27.","DOI":"10.3390\/molecules27144360"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pistelli, L., Del Mondo, A., Smerilli, A., Corato, F., Sansone, C., and Brunet, C. (2023). Biotechnological response curve of the cyanobacterium Spirulina subsalsa to light energy gradient. Biotechnol. Biofuels Bioprod., 16.","DOI":"10.1186\/s13068-023-02277-4"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nbt0705-833","article-title":"Summary recommendations for standardization and reporting of metabolic analyses","volume":"23","author":"Lindon","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101830","DOI":"10.1016\/j.algal.2020.101830","article-title":"Value-added co-products from biomass of the diatoms Staurosirella pinnata and Phaeodactylum tricornutum","volume":"47","author":"Savio","year":"2020","journal-title":"Algal Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wishart, D.S., Cheng, L.L., Copi\u00e9, V., Edison, A.S., Eghbalnia, H.R., Hoch, J.C., Gouveia, G.J., Pathmasiri, W., Powers, R., and Schock, T.B. (2022). NMR and Metabolomics-A Roadmap for the Future. Metabolites, 12.","DOI":"10.3390\/metabo12080678"},{"key":"ref_30","first-page":"389","article-title":"Tangeretin Triggers Melanogenesis through the Activation of Melanogenic Signaling Proteins and Sustained Extracellular Signal-Regulated Kinase in B16\/F10 Murine Melanoma Cells","volume":"10","author":"Yoon","year":"2015","journal-title":"Nat. Prod. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2174\/1871527321666220127141611","article-title":"Role of Unani Polyherbal Formulations in the Treatment of Diseases with Special Reference to Neurodegenerative Disorders","volume":"22","author":"Siddique","year":"2023","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_32","first-page":"237","article-title":"In vitro study: Catechins as depigmenting agents inhibit melanogenesis on B16F0 cells","volume":"13","author":"Widyastuti","year":"2020","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bej.2013.01.005","article-title":"Inhibitory effect of ectoine on melanogenesis in B16-F0 and A2058 melanoma cell lines","volume":"78","author":"Yao","year":"2013","journal-title":"Biochem. Eng. J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kim, K., Huh, Y., and Lim, K.M. (2021). Anti-Pigmentary Natural Compounds and Their Mode of Action. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126206"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6669","DOI":"10.1111\/jocd.15437","article-title":"Potential application of natural bioactive compounds as skin-whitening agents: A review","volume":"21","author":"Zhao","year":"2022","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s11418-018-1171-4","article-title":"Melanogenesis inhibitory activity of components from Salam leaf (Syzygium polyanthum) extract","volume":"72","author":"Setyawati","year":"2018","journal-title":"J. Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3109\/10799893.2011.583254","article-title":"Mediation of cholino-piperine like receptors by extracts of Piper nigrum induces melanin dispersion in Rana tigerina tadpole melanophores","volume":"31","author":"Sajid","year":"2011","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jmau.2015.07.001","article-title":"Understanding the ultrastructural aspects of berberine-induced skin-darkening activity in the toad, Bufo melanostictus, melanophores","volume":"3","author":"Ali","year":"2015","journal-title":"J. Microsc. Ultrastruct."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"847","DOI":"10.5530\/pj.2022.14.178","article-title":"In Silico Study of Naringenin as Melanogenesis Inducer in Vitiligo","volume":"14","author":"Ardiana","year":"2022","journal-title":"Pharmacogn. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Jeung, D., Lee, G.E., Chen, W., Byun, J., Nam, S.B., Park, Y.M., Lee, H.S., Kang, H.C., Lee, J.Y., and Kim, K.D. (2024). Ribosomal S6 kinase 2-forkhead box protein O4 signaling pathway plays an essential role in melanogenesis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-60165-9"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Menichetti, A., Mordini, D., Vicenzi, S., Pane, A., and Montalti, M. (2025). Unexplored Mechanisms of Photoprotection: Synergistic Light Absorption and Antioxidant Activity of Melanin. Antioxidants, 14.","DOI":"10.3390\/antiox14040376"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.molcel.2010.02.020","article-title":"ERK2 but not ERK1 induces epithelial-to-mesenchymal transformation via DEF motif-dependent signaling events","volume":"38","author":"Shin","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/pcmr.13165","article-title":"The metabolism of melanin synthesis\u2014From melanocytes to melanoma","volume":"37","author":"Snyman","year":"2024","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bogdan, C., Molnar, M., Dima, E.I., Olteanu, A.A., Safta, D.A., and Moldovan, M.-L. (2025). Marine Macroalgae in Topical Formulations: Bioactive Compounds, Variability, Analytical Challenges and Skin Benefits. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17091143"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wang, F., Ma, W., Fan, D., Hu, J., An, X., and Wang, Z. (2024). The biochemistry of melanogenesis: An insight into the function and mechanism of melanogenesis-related proteins. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1440187"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1039\/C9NP00011A","article-title":"Synergy and antagonism in natural product extracts: When 1 + 1 does not equal 2","volume":"36","author":"Caesar","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.2741\/4861","article-title":"Protein kinases as regulators of osmolyte accumulation under stress conditions: An overview","volume":"25","author":"Manzoor","year":"2020","journal-title":"Front. Biosci."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, M., Huang, J., Zheng, D., Tang, H., Liu, J., Luo, J., and Wen, X. (2024). ERK1\/2 regulates melanin synthesis in fish: A case study on a colourful variety, leopard coral grouper (Plectropomus leopardus). Front. Mar. Sci., 11.","DOI":"10.3389\/fmars.2024.1441589"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22493","DOI":"10.1021\/acsami.4c01513","article-title":"Quaternary Ammonium Assisted Synthesis of Melanin-like Poly (l-DOPA) Nanoparticles with a Boosted Photothermal Effect","volume":"16","author":"Wang","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s40257-024-00863-2","article-title":"An Update on New and Existing Treatments for the Management of Melasma","volume":"25","author":"Gan","year":"2024","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.2147\/CCID.S485237","article-title":"Azelaic Acid: Mechanisms of Action and Clinical Applications","volume":"17","author":"Feng","year":"2024","journal-title":"Clin. Cosmet. Investig. Dermatol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/12\/1402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:13:09Z","timestamp":1764220389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/12\/1402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["antiox14121402"],"URL":"https:\/\/doi.org\/10.3390\/antiox14121402","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2025,11,25]]}}}