Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway
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....
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MDPI AG
2022-09-01
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Online Access: | https://www.mdpi.com/2072-6643/14/18/3713 |
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author | Jeong-Hyun Yoon Kumju Youn Mira Jun |
author_facet | Jeong-Hyun Yoon Kumju Youn Mira Jun |
author_sort | Jeong-Hyun Yoon |
collection | DOAJ |
description | 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 β-catenin by cAMP/PKA-mediated GSK-3β inactivation. Co-treatment with a PKA inhibitor, inhibited melanin production, tyrosinase activity, and expression of MITF, <i>p</i>-CREB, <i>p</i>-GSK-3β and <i>p</i>-β-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. |
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spelling | doaj.art-a8cf625c3ca4465ab22241aea750d9a22023-11-23T18:10:30ZengMDPI AGNutrients2072-66432022-09-011418371310.3390/nu14183713Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling PathwayJeong-Hyun Yoon0Kumju Youn1Mira Jun2Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, KoreaDepartment of Food Science and Nutrition, Dong-A University, Busan 49315, KoreaDepartment of Health Sciences, The Graduate School of Dong-A University, Busan 49315, KoreaMelanogenesis 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 β-catenin by cAMP/PKA-mediated GSK-3β inactivation. Co-treatment with a PKA inhibitor, inhibited melanin production, tyrosinase activity, and expression of MITF, <i>p</i>-CREB, <i>p</i>-GSK-3β and <i>p</i>-β-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.https://www.mdpi.com/2072-6643/14/18/3713melanogenesispinostrobinMITFmelanogenesis-related enzymecAMP/PKAp38 |
spellingShingle | Jeong-Hyun Yoon Kumju Youn Mira Jun Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway Nutrients melanogenesis pinostrobin MITF melanogenesis-related enzyme cAMP/PKA p38 |
title | Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway |
title_full | Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway |
title_fullStr | Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway |
title_full_unstemmed | Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway |
title_short | Discovery of Pinostrobin as a Melanogenic Agent in cAMP/PKA and p38 MAPK Signaling Pathway |
title_sort | discovery of pinostrobin as a melanogenic agent in camp pka and p38 mapk signaling pathway |
topic | melanogenesis pinostrobin MITF melanogenesis-related enzyme cAMP/PKA p38 |
url | https://www.mdpi.com/2072-6643/14/18/3713 |
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