{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:22:06Z","timestamp":1780384926818,"version":"3.54.1"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2021R1F1A1059925"],"award-info":[{"award-number":["2021R1F1A1059925"]}]},{"name":"Ministry of Education","award":["2021R1F1A1059925"],"award-info":[{"award-number":["2021R1F1A1059925"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>UV light causes excessive oxidative stress and abnormal melanin synthesis, which results in skin hyperpigmentation disorders such as freckles, sunspots, and age spots. Much research has been carried out to discover natural plants for ameliorating these disorders. Aronia melanocarpa contains various polyphenolic compounds with antioxidative activities, but its effects on melanogenesis have not been fully elucidated. In this study, we investigated the inhibitory effect of fermented Aronia melanocarpa (FA) fermented with Monascus purpureus on melanogenesis and its underlying mechanism in the B16F10 melanoma cell line. Our results indicate that FA inhibited tyrosinase activity and melanogenesis in alpha-melanocyte-stimulating hormone (\u03b1-MSH)-induced B16F10 cells. FA significantly downregulated the PKA\/CREB pathway, resulting in decreased protein levels of tyrosinase, TRP-1, and MITF. FA also inhibited the transcription of MITF by increasing the phosphorylation levels of both GSK3\u03b2 and AKT. Interestingly, we demonstrated that these results were owing to the significant increase in gallic acid, a phenolic compound of Aronia melanocarpa produced after the fermentation of Monascus purpureus. Taken together, our research suggests that Aronia melanocarpa fermented with Monascus purpureus acts as a melanin inhibitor and can be used as a potential cosmetic or therapeutic for improving hyperpigmentation disorders.<\/jats:p>","DOI":"10.3390\/molecules28072981","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T06:46:19Z","timestamp":1679899579000},"page":"2981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Fermented Aronia melanocarpa Inhibits Melanogenesis through Dual Mechanisms of the PI3K\/AKT\/GSK-3\u03b2 and PKA\/CREB Pathways"],"prefix":"10.3390","volume":"28","author":[{"given":"Da Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1262-2566","authenticated-orcid":false,"given":"Dong Wook","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9618-5956","authenticated-orcid":false,"given":"Beong Ou","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1210\/en.2017-03230","article-title":"How UV Light Touches the Brain and Endocrine System Through Skin, and Why","volume":"159","author":"Slominski","year":"2018","journal-title":"Endocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8293","DOI":"10.3390\/ijms15058293","article-title":"Inhibitors of intracellular signaling pathways that lead to stimulated epidermal pigmentation: Perspective of anti-pigmenting agents","volume":"15","author":"Imokawa","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"842496","DOI":"10.3389\/fonc.2022.842496","article-title":"Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship","volume":"12","author":"Slominski","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/exd.13844","article-title":"Melasma: Updates and perspectives","volume":"28","author":"Kwon","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7178305","DOI":"10.1155\/2021\/7178305","article-title":"Diagnosis and Management of Lentigo Maligna: Clinical Presentation and Comprehensive Review","volume":"2021","author":"Naik","year":"2021","journal-title":"J. Skin Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1755-148X.2011.00898.x","article-title":"L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions","volume":"25","author":"Slominski","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"D\u2019Mello, S.A., 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_9","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1038\/skinbio.2011.1","article-title":"Milestones in melanocytes\/melanogenesis","volume":"131","author":"Hearing","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1038\/jid.2014.548","article-title":"p21-activated kinase 4 critically regulates melanogenesis via activation of the CREB\/MITF and \u03b2-catenin\/MITF pathways","volume":"135","author":"Yun","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s00125-015-3504-0","article-title":"A survival Kit for pancreatic beta cells: Stem cell factor and c-Kit receptor tyrosine kinase","volume":"58","author":"Feng","year":"2015","journal-title":"Diabetologia"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, P.H., Liu, L.H., Chang, C.C., Gao, R., Leung, C.H., Ma, D.L., and DavidWang, H.M. (2018). Silencing stem cell factor gene in fibroblasts to regulate paracrine factor productions and enhance c-kit expression in melanocytes on melanogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051475"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/pcmr.12430","article-title":"A novel synthetic Piper amide derivative NED-180 inhibits hyperpigmentation by activating the PI 3K and ERK pathways and by regulating Ca2+ influx via TRPM 1 channels","volume":"29","author":"Hwang","year":"2016","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"154449","DOI":"10.1016\/j.phymed.2022.154449","article-title":"The melanin inhibitory effect of plants and phytochemicals: A systematic review","volume":"107","author":"Feng","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.2174\/1381612825666190703153730","article-title":"Depigmentation and Anti-aging Treatment by Natural Molecules","volume":"25","author":"Zaid","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1055\/a-0583-0410","article-title":"Plants and Natural Products for the Treatment of Skin Hyperpigmentation\u2014A Review","volume":"84","author":"Kanlayavattanakul","year":"2018","journal-title":"Planta Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Oszmianski, J., and Lachowicz, S. (2016). Effect of the Production of Dried Fruits and Juice from Chokeberry (Aronia melanocarpa L.) on the Content and Antioxidative Activity of Bioactive Compounds. Molecules, 21.","DOI":"10.3390\/molecules21081098"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jurikova, T., Mlcek, J., Skrovankova, S., Sumczynski, D., Sochor, J., Hlavacova, I., Snopek, L., and Orsavova, J. (2017). Fruits of black chokeberry Aronia melanocarpa in the prevention of chronic disease. Molecules, 22.","DOI":"10.3390\/molecules22060944"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1002\/ptr.6398","article-title":"The effect of Aronia consumption on lipid profile, blood pressure, and biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials","volume":"33","author":"Rahmani","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.nutres.2013.03.001","article-title":"Aronia melanocarpa (chokeberry) polyphenol\u2013rich extract improves antioxidant function and reduces total plasma cholesterol in apolipoprotein E knockout mice","volume":"33","author":"Kim","year":"2013","journal-title":"Nutr. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1111\/1750-3841.14660","article-title":"Phenolic composition, radical scavenging activity and an approach for authentication of Aronia melanocarpa berries, juice, and pomace","volume":"84","author":"Winterhalter","year":"2019","journal-title":"J. Food Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.7150\/ijbs.9672","article-title":"Flavonoids and Melanins: A common strategy across two kingdoms","volume":"10","author":"Carletti","year":"2014","journal-title":"Int. J. Biol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.fitote.2016.04.001","article-title":"Populus nigra (Salicaceae) absolute rich in phenolic acids, phenylpropano\u00efds and flavonoids as a new potent tyrosinase inhibitor","volume":"111","author":"Maack","year":"2016","journal-title":"Fitoterapia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1016\/j.bmcl.2017.06.011","article-title":"Synthesis and biological evaluation of caffeic acid derivatives as potent inhibitors of \u03b1-MSH-stimulated melanogenesis","volume":"27","author":"Jo","year":"2017","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.foodchem.2017.10.086","article-title":"Improving free, conjugated, and bound phenolic fractions in fermented oats (Avena sativa L.) with Monascus anka","volume":"245","author":"Bei","year":"2018","journal-title":"Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"125269","DOI":"10.1016\/j.foodchem.2019.125269","article-title":"Dynamic changes in the phenolic composition and antioxidant activity of oats during simultaneous hydrolysis and fermentation","volume":"305","author":"Bei","year":"2020","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7245","DOI":"10.1021\/jf3009958","article-title":"In vitro inhibitory effect on pancreatic lipase activity of subfractions from ethanol extracts of fermented Oats (Avena sativa L.) and synergistic effect of three phenolic acids","volume":"60","author":"Cai","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103687","DOI":"10.1016\/j.fgb.2022.103687","article-title":"Investigation of citrinin and monacolin K gene clusters variation among pigment producer Monascus species","volume":"160","author":"Liu","year":"2022","journal-title":"Fungal Genet. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.lfs.2017.10.009","article-title":"An inhibitory mechanism of action of a novel syringic-acid derivative on \u03b1-melanocyte\u2013stimulating hormone (\u03b1-MSH)-induced melanogenesis","volume":"191","author":"Jeong","year":"2017","journal-title":"Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/gtc.12654","article-title":"Pyruvic acid\/ethyl pyruvate inhibits melanogenesis in B16F10 melanoma cells through PI3K\/AKT, GSK3beta, and ROS-ERK signaling pathways","volume":"24","author":"Zhou","year":"2019","journal-title":"Genes Cells"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1002\/jssc.201700477","article-title":"Fingerprint profiles of flavonoid compounds from different Psidium guajava leaves and their antioxidant activities","volume":"40","author":"Wang","year":"2017","journal-title":"J. Sep. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/biof.1064","article-title":"In vitro and in vivo studies disclosed the depigmenting effects of gallic acid: A novel skin lightening agent for hyperpigmentary skin diseases","volume":"39","author":"Kumar","year":"2013","journal-title":"Biofactors"},{"key":"ref_33","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_34","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_35","doi-asserted-by":"crossref","unstructured":"Seelam, S.D., Agsar, D., Shetty, P.R., Vemireddy, S., Reddy, K.M., Umesh, M.K., and Rajitha, C.H. (2021). Characterization and photoprotective potentiality of lime dwelling Pseudomonas mediated melanin as sunscreen agent against UV-B radiations. J. Photochem. Photobiol. B, 216.","DOI":"10.1016\/j.jphotobiol.2021.112126"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1111\/j.1751-1097.2012.01138.x","article-title":"Shining light on skin pigmentation: The darker and the brighter side of effects of UV radiation","volume":"88","author":"Maddodi","year":"2012","journal-title":"Photochem. Photobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/pcmr.12511","article-title":"The impact of skin colour on human photobiological responses","volume":"29","author":"Fajuyigbe","year":"2016","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Rok, J., Rzepka, Z., Kowalska, J., Banach, K., Beberok, A., and Wrze\u015bniok, D. (2021). Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation-The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073755"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Solano, F. (2020). Photoprotection and skin pigmentation: Melanin-related molecules and some other new agents obtained from natural sources. Molecules, 25.","DOI":"10.3390\/molecules25071537"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1755-148X.2010.00764.x","article-title":"The deceptive nature of UVA tanning versus the modest protective effects of UVB tanning on human skin","volume":"24","author":"Miyamura","year":"2011","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.molmed.2006.07.008","article-title":"MITF: Master regulator of melanocyte development and melanoma oncogene","volume":"12","author":"Levy","year":"2006","journal-title":"Trends Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19914","DOI":"10.1038\/srep19914","article-title":"Microtubule-associated protein light chain 3 is involved in melanogenesis via regulation of MITF expression in melanocytes","volume":"6","author":"Yun","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1242\/dev.031989","article-title":"FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism","volume":"136","author":"Thomas","year":"2009","journal-title":"Development"},{"key":"ref_44","first-page":"1362","article-title":"Oridonin inhibits migration, invasion, adhesion and TGF-\u03b21-induced epithelial-mesenchymal transition of melanoma cells by inhibiting the activity of PI3K\/Akt\/GSK-3\u03b2 signaling pathway","volume":"15","author":"Li","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00403-011-1155-7","article-title":"Aromatic-turmerone inhibits \u03b1-MSH and IBMX-induced melanogenesis by inactivating CREB and MITF signaling pathways","volume":"303","author":"Park","year":"2011","journal-title":"Arch. Dermatol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Choi, H., Yoon, J.H., Youn, K., and Jun, M. (2022). Decursin prevents melanogenesis by suppressing MITF expression through the regulation of PKA\/CREB, MAPKs, and PI3K\/Akt\/GSK-3\u03b2 cascades. Biomed. Pharmacother., 147.","DOI":"10.1016\/j.biopha.2022.112651"},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1111\/1541-4337.12221","article-title":"Chokeberries (Aronia melanocarpa) and their products as a possible means for the prevention and treatment of noncommunicable diseases and unfavorable health effects due to exposure to xenobiotics","volume":"15","author":"Borowska","year":"2016","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.foodchem.2013.09.029","article-title":"Determination of chokeberry (Aronia melanocarpa) polyphenol components using liquid chromatography-tandem mass spectrometry: Overall contribution to antioxidant activity","volume":"146","author":"Lee","year":"2014","journal-title":"Food Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/7\/2981\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:03:59Z","timestamp":1760123039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/7\/2981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,27]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["molecules28072981"],"URL":"https:\/\/doi.org\/10.3390\/molecules28072981","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,27]]}}}