{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T03:03:26Z","timestamp":1776135806395,"version":"3.50.1"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ratchadaphiseksomphot Endowment Fund for Postdoctoral Fellowship","award":["2567"],"award-info":[{"award-number":["2567"]}]},{"name":"the Thailand Science Research and Innovation Fund Chulalongkorn University","award":["FOOD_FF_68_050_2300_012"],"award-info":[{"award-number":["FOOD_FF_68_050_2300_012"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Melanin, synthesized by tyrosinase (TYR), is a natural pigment essential for skin protection and pigmentation. However, excessive melanin production can cause dermatological disorders. Safflospermidines, comprised of safflospermidine A and B isomers isolated from sunflower (<jats:italic>Helianthus annuus<\/jats:italic> L.) bee pollen, were shown to exhibit a strong <jats:italic>in vitro<\/jats:italic> TYR inhibitory activity against mushroom TYR. However, their anti-melanogenesis activity in cellular and <jats:italic>in vivo<\/jats:italic> models remains unexplored. This study firstly evaluated the effects of these safflospermidines on melanogenesis in \u03b1-melanocyte stimulating hormone-stimulated B16F10 cells, using kojic acid as a positive control. Cytotoxicity was evaluated using the MTT assay, while TYR activity and melanin content were measured to assess melanogenesis inhibition. The expression of key melanogenesis-related genes was analyzed through quantitative real-time reverse transcription (RT-q)PCR to elucidate the molecular mechanisms involved. Secondly, the melanogenic activity and potential toxicity of the compounds were confirmed in zebrafish embryos, with phenylthiourea (PTU) as a reference. The results revealed that a mixture of these two safflospermidines exhibited no cytotoxicity across the treated concentration range (0\u2013500 \u00b5g\/mL). At 62.5 \u00b5g\/mL, safflospermidines significantly reduced the intracellular melanin content by 21.78\u2009\u00b1\u20094.01% and the TYR activity by 25.71\u2009\u00b1\u20093.08% in B16F10 cells through downregulation of <jats:italic>TYR<\/jats:italic>, TYR-related protein 1 (<jats:italic>TRP-1<\/jats:italic>), and <jats:italic>TRP-2<\/jats:italic> gene expression. Additionally, the safflospermidines induced a noticeable reduction in dendritic cell structures, which likely contributed to the marked decrease in extracellular melanin levels. Kojic acid (250 \u03bcg\/mL) significantly reduced the melanin content and TYR activity by suppressing all three melanogenesis-related genes. In zebrafish embryos, safflospermidines showed no toxicity or morphological abnormalities within a concentration range of 0\u201362.5 \u00b5g\/mL, and at a concentration of 15.63 \u00b5g\/mL the melanin production in zebrafish embryos was significantly reduced by 28.43\u2009\u00b1\u20099.17%. In comparison, 0.0015% (v\/v) PTU decreased melanin production by 53.20\u2009\u00b1\u20093.75%. These findings suggest that safflospermidines are safe, effective melanin inhibitors with potential applications in pharmaceuticals and cosmetics for managing hyperpigmentation.<\/jats:p>","DOI":"10.1371\/journal.pone.0325264","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:33:42Z","timestamp":1750786422000},"page":"e0325264","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The in cellular and in vivo melanogenesis inhibitory activity of safflospermidines from Helianthus annuus L. bee pollen in B16F10 murine melanoma cells and zebrafish 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