{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:01:56Z","timestamp":1792670516809,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dong-A University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Melanogenesis is the process of melanin synthesis to protect the skin against ultraviolet radiation and other external stresses. The loss of skin pigmentation is closely related to depigmented skin disorders. The melanogenic effects of pinostrobin, an active flavanone found in honey, were evaluated. B16F10 cells were used for melanin content, tyrosinase activity, and the expression of melanogenesis-related markers. Moreover, computational simulations were performed to predict docking and pharmacokinetics. Pinostrobin increased melanin levels and tyrosinase activity by stimulating the expression of melanogenic regulatory factors including tyrosinase, tyrosinase-related protein (TRP) 1 and microphthalmia transcription factor (MITF). Specifically, the phosphorylation of cAMP response element binding (CREB) involved in the MITF activation was augmented by pinostrobin. Moreover, the compound upregulated the \u03b2-catenin by cAMP\/PKA-mediated GSK-3\u03b2 inactivation. Co-treatment with a PKA inhibitor, inhibited melanin production, tyrosinase activity, and expression of MITF, p-CREB, p-GSK-3\u03b2 and p-\u03b2-catenin, demonstrating that pinostrobin-stimulated melanogenesis was closely related to cAMP\/PKA signaling pathway. Furthermore, the combination of pinostrobin and a specific p38 inhibitor, showed that MITF upregulation by pinostrobin was partly associated with the p38 signaling pathway. Docking simulation exhibited that the oxygen group at C-4 and the hydroxyl group at C-5 of pinostrobin may play an essential role in melanogenesis. In silico analysis revealed that pinostrobin had the optimal pharmacokinetic profiles including gastrointestinal absorption, skin permeability, and inhibition of cytochrome (CYP) enzymes. From the present results, it might be suggested that pinostrobin could be useful as a potent and safe melanogenic agent in the depigmentation disorder, vitiligo.<\/jats:p>","DOI":"10.3390\/nu14183713","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T04:05:41Z","timestamp":1663041941000},"page":"3713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Discovery of Pinostrobin as a Melanogenic Agent in cAMP\/PKA and p38 MAPK Signaling Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Jeong-Hyun","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-2665","authenticated-orcid":false,"given":"Kumju","family":"Youn","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Dong-A University, Busan 49315, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Korea"},{"name":"Department of Food Science and Nutrition, Dong-A University, Busan 49315, Korea"},{"name":"Center for Food & Bio Innovation, Dong-A University, Busan 49315, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S1011-1344(98)00182-1","article-title":"Changes in biologically active ultraviolet radiation reaching the Earth\u2019s surface","volume":"46","author":"Madronich","year":"1998","journal-title":"J. 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