{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:04:20Z","timestamp":1779311060749,"version":"3.51.4"},"reference-count":69,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Science and Technology Agency (JST)","award":["JPMJSA1506"],"award-info":[{"award-number":["JPMJSA1506"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyperpigmentation is a skin condition where patches of skin become darker in color due to excess melanin production upon UV exposure leading to melasma, which are lentigines or post inflammatory hyperpigmentation that psychologically affecting a great number of people. The present study investigates the anti-melanogenic effect of Butyroside D and the underling mechanism. After the confirmation of the non-cytotoxic effect of Butyroside D on B16F10 cells, we proceeded with analyzing the impact of the treatment at low and high concentration (i.e., 0.2 \u03bcM and 2 \u03bcM) using gene profiling analysis and examined the differentiation in gene expression. Our results identify cyclic adenosine monophosphate (cAMP), Wnt\/\u03b2-catenin and Mitogen-Activated Protein Kinase (MAPK) signaling pathways to be downregulated upon treatment with Butyroside D. These pathways were targeted to further validate the effect of Butyroside D on membrane receptors melanocortin 1 receptor (MC1R) and receptor tyrosine kinase (c-Kit), related microphthalmia-associated transcription factor (MITF) and consequently tyrosinase (TYR), and tyrosine-related protein-1 (TYRP-1) that were all shown to be downregulated and, therefore, leading to the repression of melanin biosynthesis. Finally, the anti-melanogenic effect of Butyroside D was confirmed on human epidermal melanocytes (HEM) cells by inhibiting the activation of cAMP pathway generally mediated through \u03b1-melanocyte-stimulating hormone (\u03b1-MSH) and MC1R. Overall, this study suggests the potential applicability of this purified compound for the prevention of hyperpigmentation conditions.<\/jats:p>","DOI":"10.3390\/ijms232416021","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T04:30:00Z","timestamp":1671165000000},"page":"16021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["New Butyroside D from Argan Press Cake Possess Anti-Melanogenesis Effect via MITF Downregulation in B16F10 and HEM Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7089-130X","authenticated-orcid":false,"given":"Meryem","family":"Bouhoute","sequence":"first","affiliation":[{"name":"Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-0006, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2552-4567","authenticated-orcid":false,"given":"Yhiya","family":"Amen","sequence":"additional","affiliation":[{"name":"Department of Agro-Environmental Sciences, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meriem","family":"Bejaoui","sequence":"additional","affiliation":[{"name":"Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-0006, Japan"},{"name":"Research and Development Center for Tailor-Made QOL Program, University of Tsukuba, Tsukuba 305-8550, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8242-635X","authenticated-orcid":false,"given":"Aprill Kee Oliva","family":"Mizushima","sequence":"additional","affiliation":[{"name":"Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-0006, Japan"},{"name":"Research and Development Center for Tailor-Made QOL Program, University of Tsukuba, Tsukuba 305-8550, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5960-1503","authenticated-orcid":false,"given":"Kuniyoshi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Agro-Environmental Sciences, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-9541","authenticated-orcid":false,"given":"Hiroko","family":"Isoda","sequence":"additional","affiliation":[{"name":"Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-0006, Japan"},{"name":"Research and Development Center for Tailor-Made QOL Program, University of Tsukuba, Tsukuba 305-8550, Japan"},{"name":"Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/pcmr.12080","article-title":"Cellular and molecular mechanisms controlling the migration of melanocytes and melanoma cells","volume":"26","author":"Bonaventure","year":"2013","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/dvdy.1153","article-title":"Agouti signaling protein and other factors modulating differentiation and proliferation of immortal melanoblasts","volume":"221","author":"Sviderskaya","year":"2001","journal-title":"Dev. Dyn."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1590\/S0365-05962013000100009","article-title":"Mechanisms Regulating Melanogenesis","volume":"88","author":"Videira","year":"2013","journal-title":"An. Bras. Dermatol."},{"key":"ref_4","first-page":"4183","article-title":"Synthesis and physiological implications of melanic pigments (Review)","volume":"17","author":"Maranduca","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/35096009","article-title":"The melanosome: Membrane dynamics in black and white","volume":"2","author":"Marks","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27557","DOI":"10.1074\/jbc.R700026200","article-title":"The Regulation of Skin Pigmentation","volume":"282","author":"Yamaguchi","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lv, J., Yang, Y., Jia, B., Li, S., Zhang, X., and Gao, R. (2021). The Inhibitory Effect of Curcumin Derivative J147 on Melanogenesis and Melanosome Transport by Facilitating ERK-Mediated MITF Degradation. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.783730"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7395","DOI":"10.1021\/acs.jmedchem.7b00967","article-title":"Inhibitors of Melanogenesis: An Updated Review","volume":"61","author":"Pillaiyar","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14821","DOI":"10.1074\/jbc.M111497200","article-title":"Abnormal Acidification of Melanoma Cells Induces Tyrosinase Retention in the Early Secretory Pathway","volume":"277","author":"Halaban","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/ced.14747","article-title":"Differential diagnosis and management of hyperpigmentation","volume":"47","author":"Yoo","year":"2022","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.1002\/j.1460-2075.1994.tb06925.x","article-title":"Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis","volume":"13","author":"Kobayashi","year":"1994","journal-title":"EMBO J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cellsig.2017.09.004","article-title":"Recent development of signaling pathways inhibitors of melanogenesis","volume":"40","author":"Pillaiyar","year":"2017","journal-title":"Cell Signal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nchembio.1548","article-title":"Multifaceted pathways protect human skin from UV radiation","volume":"10","author":"Natarajan","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"D\u2019Mello, S.A.N., Finlay, G.J., Baguley, B.C., and Askarian-Amiri, M.E. (2016). Signaling Pathways in Melanogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071144"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1751-1097.2007.00226.x","article-title":"The Protective Role of Melanin Against UV Damage in Human Skin","volume":"84","author":"Brenner","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.jep.2011.07.047","article-title":"Partially purified components of Nardostachys chinensis suppress melanin synthesis through ERK and Akt signaling pathway with cAMP down-regulation in B16F10 cells","volume":"137","author":"Jang","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jep.2018.08.007","article-title":"Effects on skin of Stichopus japonicus viscera extracts detected with saponin including Holothurin A: Down-regulation of melanin synthesis and up-regulation of neocollagenesis mediated by ERK signaling pathway","volume":"226","author":"Kwon","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.toxrep.2018.11.005","article-title":"Anti-melanogenic and anti-oxidant activities of ethanol extract of Kummerowia striata: Kummerowia striata regulate anti-melanogenic activity through down-regulation of TRP-1, TRP-2 and MITF expression","volume":"6","author":"Lee","year":"2018","journal-title":"Toxicol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Taarji, N., Bouhoute, M., Melanie, H., Hafidi, A., Kobayashi, I., Neves, M., Tominaga, K., Isoda, H., and Nakajima, M. (2020). Stability characteristics of O\/W emulsions prepared using purified glycyrrhizin or a non-purified glycyrrhizin-rich extract from liquorice root (Glycyrrhiza glabra). Coll. Surf. A Physicochem. Eng. Asp., 614.","DOI":"10.1016\/j.colsurfa.2020.126006"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lee, K.W., Kim, M., Lee, S.H., and Kim, K.D. (2022). The Function of Autophagy as a Regulator of Melanin Homeostasis. Cells, 11.","DOI":"10.3390\/cells11132085"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Taarji, N., Bouhoute, M., Fainassi, F., Hafidi, A., Kobayashi, I., Neves, M.A., Tominaga, K., Isoda, H., and Nakajima, M. (2021). Interfacial and emulsifying properties of purified glycyrrhizin and non-purified glycyrrhizin-rich extracts from liquorice root (Glycyrrhiza glabra). Food Chem., 337.","DOI":"10.1016\/j.foodchem.2020.127949"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1021\/acsfoodscitech.1c00208","article-title":"Emulsifying Performance of Crude Surface-Active Extracts from Liquorice Root (Glycyrrhiza Glabra)","volume":"1","author":"Taarji","year":"2021","journal-title":"ACS Food Sci. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mechqoq, H., El Yaagoubi, M., El Hamdaoui, A., Momchilova, S., Almeida, J.R.G.D.S., Msanda, F., and El Aouad, N. (2021). Ethnobotany, phytochemistry and biological properties of Argan tree (Argania spinosa (L.) Skeels) (Sapotaceae)\u2014A review. J. Ethnopharmacol., 281.","DOI":"10.1016\/j.jep.2021.114528"},{"key":"ref_24","first-page":"649","article-title":"Phytochemical analysis and antibacterial activity towards methicillin-resistant Staphylococcus aureus of leaf extracts from Argania spinosa (L.) Skeels","volume":"151","author":"Bonvicini","year":"2017","journal-title":"Plant Biosyst. Int. J. Deal. All Asp. Plant Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bouhoute, M., Nakajima, M., and Isoda, H. (2021). Design of nanoemulgel using Argania spinosa microfibrillated cellulose and natural emulsifiers foreseeing melanogenesis enhancement. Carbohydr. Polym., 274.","DOI":"10.1016\/j.carbpol.2021.118632"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bouhoute, M., Taarji, N., Vodo, S., Kobayashi, I., Zahar, M., Isoda, H., Nakajima, M., and Neves, M.A. (2020). Formation and stability of emulsions using crude extracts as natural emulsifiers from Argan shells. Colloids Surfaces A Physicochem. Eng. Asp., 591.","DOI":"10.1016\/j.colsurfa.2020.124536"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Makbal, R., Villareal, M.O., Gadhi, C., Hafidi, A., and Isoda, H. (2020). Argania Spinosa Fruit Shell Extract-Induced Melanogenesis via cAMP Signaling Pathway Activation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072539"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"340107","DOI":"10.1155\/2013\/340107","article-title":"Activation of MITF by Argan Oil Leads to the Inhibition of the Tyrosinase and Dopachrome Tautomerase Expressions in B16 Murine Melanoma Cells","volume":"2013","author":"Villareal","year":"2013","journal-title":"Evidence-Based Complement. Altern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1007\/s10616-018-0232-6","article-title":"Depigmenting effect of argan press-cake extract through the down-regulation of Mitf and melanogenic enzymes expression in B16 murine melanoma cells","volume":"70","author":"Bourhim","year":"2018","journal-title":"Cytotechnology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bouhoute, M., Taarji, N., De Oliveira Felipe, L., Habibi, Y., Kobayashi, I., Zahar, M., Isoda, H., Nakajima, M., and Neves, M.A. (2021). Microfibrillated cellulose from Argania spinosa shells as sustainable solid particles for O\/W Pickering emulsions. Carbohydr. Polym., 251.","DOI":"10.1016\/j.carbpol.2020.116990"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Taarji, N., Vodo, S., Bouhoute, M., Khalid, N., Hafidi, A., Kobayashi, I., Neves, M.A., Isoda, H., and Nakajima, M. (2020). Preparation of monodisperse O\/W emulsions using a crude surface-active extract from argan by-products in microchannel emulsification. Coll. Surf. A Physicochem. Eng. Asp., 585.","DOI":"10.1016\/j.colsurfa.2019.124050"},{"key":"ref_32","first-page":"43","article-title":"Triterpenoids from Argania spinosa: 20 Years of Research","volume":"8","author":"Charrouf","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/cbdv.201400328","article-title":"Argania spinosavar.muticaand var.apiculata:Variation of Fatty-Acid Composition, Phenolic Content, and Antioxidant and\u03b1-Amylase-Inhibitory Activities among Varieties, Organs, and Development Stages","volume":"12","author":"Aissi","year":"2015","journal-title":"Chem. Biodivers."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ezzahra, F., Bousta, D., Imtara, H., Lahrichi, A., Elhabbani, R., El, G., Al, O., Saleh, A., Parvez, M.K., and Grafov, A. (2022). Chemical Composition and Anti-Urolithiatic Activity of Extracts from Argania Spinosa (L.) Skeels Press-Cake and Acacia Senegal (L.) Willd. Molecules, 27.","DOI":"10.3390\/molecules27133973"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/pca.2440","article-title":"Saponin Inventory from Argania spinosa Kernel Cakes by Liquid Chromatography and Mass Spectrometry","volume":"24","author":"Henry","year":"2013","journal-title":"Phytochem. Anal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S0031-9422(00)90365-0","article-title":"Triterpenoid Saponins from Madhuca Butyracea","volume":"37","author":"Li","year":"1994","journal-title":"Phytochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/s41598-018-37055-y","article-title":"Quantitative analysis of melanin content in a three-dimensional melanoma cell culture","volume":"9","author":"Chung","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"30","DOI":"10.5114\/pdia.2013.33376","article-title":"Skin melanocytes: Biology and development","volume":"1","author":"Cichorek","year":"2013","journal-title":"Adv. Dermatol. Allergol."},{"key":"ref_39","first-page":"36","article-title":"Aging in Epidermal Melanocytes: Cell Cycle Genes and Melanins","volume":"3","author":"Haddad","year":"1998","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/1423-0127-18-55","article-title":"Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects","volume":"18","author":"Jeong","year":"2011","journal-title":"J. Biomed. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nature05660","article-title":"Melanocyte biology and skin pigmentation","volume":"445","author":"Lin","year":"2007","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1034\/j.1600-0749.13.s8.18.x","article-title":"Regulation of Pigment Cell-Specific Gene Expression by MITF","volume":"13","author":"Shibahara","year":"2000","journal-title":"Pigment Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e134","DOI":"10.14440\/jbm.2020.327","article-title":"A 2D and 3D melanogenesis model with human primary cells induced by tyrosine","volume":"7","author":"Branquinho","year":"2020","journal-title":"J. Biol. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26226","DOI":"10.1074\/jbc.272.42.26226","article-title":"Evidence of the Indirect Formation of the Catecholic Intermediate Substrate Responsible for the Autoactivation Kinetics of Tyrosinase","volume":"272","author":"Cooksey","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.3390\/ijms10125326","article-title":"The Hunt for Natural Skin Whitening Agents","volume":"10","author":"Smit","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Guo, J., Ma, X., Bouffard, F., and Zhang, S.Y. (2022). A Novel multi-fruit acids formula design on molecular basis for skin brightening via a system biology approach. J. Cosmet. Dermatol.","DOI":"10.1111\/jocd.15163"},{"key":"ref_47","first-page":"20","article-title":"Postinflammatory Hyperpigmentation A Review of the Epidemiology, Clinical Features, and Treatment Options in Skin of Color","volume":"3","author":"Davis","year":"2010","journal-title":"J. Clin. Aesthetic Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10616-013-9657-0","article-title":"Improved cosmetic activity by optimizing the Lithospermum erythrorhizon extraction process","volume":"67","author":"Kim","year":"2015","journal-title":"Cytotechnology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/14756366.2016.1256882","article-title":"Skin whitening agents: Medicinal chemistry perspective of tyrosinase inhibitors","volume":"32","author":"Pillaiyar","year":"2017","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1046\/j.1523-1747.2000.00860.x","article-title":"Downregulation of Tyrosinase Activity in Human Melanocyte Cell Cultures by Yohimbine","volume":"114","author":"Fuller","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/S1357-2725(97)00013-7","article-title":"Melanin","volume":"29","author":"Riley","year":"1997","journal-title":"Int. J. Bioochem. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0014-5793(91)81274-C","article-title":"POMC Gene Expression in Mouse and Hamster Melanoma Cells","volume":"291","author":"Slommsk","year":"1991","journal-title":"FEBS Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1152\/physrev.2000.80.3.979","article-title":"Corticotropin Releasing Hormone and Proopiomelanocortin Involvement in the Cutaneous Response to Stress","volume":"80","author":"Slominski","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_54","first-page":"177","article-title":"L\u2019AMP cyclique est un r\u00e9gulateur de la pigmentation de la peau","volume":"17","author":"Bertolotto","year":"2001","journal-title":"Med.\/Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/0092-8674(89)90013-5","article-title":"Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133","volume":"59","author":"Gonzalez","year":"1989","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1046\/j.1523-1747.2003.12420.x","article-title":"Microphthalmia Associated Transcription Factor Is a Target of the Phosphatidylinositol-3-Kinase Pathway","volume":"121","author":"Khaled","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1423-0127-18-74","article-title":"Antimelanogenic effect of c-phycocyanin through modulation of tyrosinase expression by upregulation of ERK and downregulation of p38 MAPK signaling pathways","volume":"18","author":"Wu","year":"2011","journal-title":"J. Biomed. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"20443","DOI":"10.3390\/ijms141020443","article-title":"Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K\/Akt, MEK\/ERK and Wnt\/\u03b2-Catenin Signaling Pathways in B16F10 Cells","volume":"14","author":"Su","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1101\/gad.14.2.158","article-title":"Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway","volume":"14","author":"Dorsky","year":"2000","journal-title":"Genes Dev."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","unstructured":"Slominski, R.M., Sarna, T., P\u0142onka, P.M., Raman, C., Bro\u017cyna, A.A., and Slominski, A.T. (2022). Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.842496"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1038\/jid.2013.235","article-title":"Wnt\/\u03b2-Catenin and Kit Signaling Sequentially Regulate Melanocyte Stem Cell Differentiation in UVB-Induced Epidermal Pigmentation","volume":"133","author":"Yamada","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e9402","DOI":"10.7717\/peerj.9402","article-title":"KIT is involved in melanocyte proliferation, apoptosis and melanogenesis in the Rex Rabbit","volume":"8","author":"Hu","year":"2020","journal-title":"PeerJ"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1742-7843.2008.00251.x","article-title":"Geniposide Enhances Melanogenesis by Stem Cell Factor\/c-Kit Signalling in Norepinephrine-Exposed Normal Human Epidermal Melanocyte","volume":"103","author":"Lan","year":"2008","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1111\/pcmr.12257","article-title":"MC1R, the cAMP pathway, and the response to solar UV: Extending the horizon beyond pigmentation","volume":"27","year":"2014","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1152\/physrev.00044.2003","article-title":"Melanin pigmentation in mammalian skin and its hormonal regulation","volume":"84","author":"Slominski","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"23420","DOI":"10.3390\/ijms141223420","article-title":"Tyrosol and Its Analogues Inhibit Alpha-Melanocyte-Stimulating Hormone Induced Melanogenesis","volume":"14","author":"Wen","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1074\/jbc.M603454200","article-title":"Peripheral Effect of \u03b1-Melanocyte-stimulating Hormone on Fatty Acid Oxidation in Skeletal Muscle","volume":"282","author":"An","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_69","first-page":"101","article-title":"Curcumin suppresses \u03b1-melanocyte stimulating hormone-stimulated melanogenesis in B16F10 cells","volume":"26","author":"Lee","year":"2010","journal-title":"Int. J. Mol. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/16021\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:33Z","timestamp":1760146953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/16021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":69,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232416021"],"URL":"https:\/\/doi.org\/10.3390\/ijms232416021","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,16]]}}}