Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells
Hyperpigmentation diseases of the skin require topical treatment with depigmenting agents. We investigated the hypopigmented mechanisms of sargahydroquinoic acid (SHQA) in alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. SHQA reduced cellular tyrosinase (TYR) activity and melani...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/2304-8158/10/10/2254 |
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| author | Mohammed Shariful Azam Jae-Il Kim Chang Geun Choi Jinkyung Choi Bonggi Lee Hyeung-Rak Kim |
| author_facet | Mohammed Shariful Azam Jae-Il Kim Chang Geun Choi Jinkyung Choi Bonggi Lee Hyeung-Rak Kim |
| author_sort | Mohammed Shariful Azam |
| collection | DOAJ |
| description | Hyperpigmentation diseases of the skin require topical treatment with depigmenting agents. We investigated the hypopigmented mechanisms of sargahydroquinoic acid (SHQA) in alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. SHQA reduced cellular tyrosinase (TYR) activity and melanin content in a concentration-dependent manner and attenuated the expression of TYR and tyrosinase-related protein 1 (TRP1), along with their transcriptional regulator, microphthalmia-associated transcription factor (MITF). SHQA also suppressed α-MSH-induced cellular production of cyclic adenosine monophosphate (cAMP), which inhibited protein kinase A (PKA)-dependent cAMP-responsive element-binding protein (CREB) activation. Docking simulation data showed a potential binding affinity of SHQA to the regulatory subunit RIIβ of PKA, which may also adversely affect PKA and CREB activation. Moreover, SHQA activated ERK1/2 signaling in B16F10 cells, stimulating the proteasomal degradation of MITF. These data suggest that SHQA ameliorated hyperpigmentation in α-MSH-stimulated B16F10 cells by downregulating MITF via PKA inactivation and ERK1/2 phosphorylation, indicating that SHQA is a potent therapeutic agent against skin hyperpigmentation disorders. |
| first_indexed | 2024-03-10T06:34:46Z |
| format | Article |
| id | doaj.art-7bf45e2a7134430d8ab0701ed9ce20e3 |
| institution | Directory Open Access Journal |
| issn | 2304-8158 |
| language | English |
| last_indexed | 2024-03-10T06:34:46Z |
| publishDate | 2021-09-01 |
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| series | Foods |
| spelling | doaj.art-7bf45e2a7134430d8ab0701ed9ce20e32023-11-22T18:13:08ZengMDPI AGFoods2304-81582021-09-011010225410.3390/foods10102254Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 CellsMohammed Shariful Azam0Jae-Il Kim1Chang Geun Choi2Jinkyung Choi3Bonggi Lee4Hyeung-Rak Kim5Department of Food Science and Nutrition, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, KoreaDepartment of Food Science and Nutrition, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, KoreaDepartment of Ecological Engineering, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, KoreaDepartment of Food Science and Nutrition, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, KoreaDepartment of Food Science and Nutrition, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, KoreaDepartment of Food Science and Nutrition, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, KoreaHyperpigmentation diseases of the skin require topical treatment with depigmenting agents. We investigated the hypopigmented mechanisms of sargahydroquinoic acid (SHQA) in alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. SHQA reduced cellular tyrosinase (TYR) activity and melanin content in a concentration-dependent manner and attenuated the expression of TYR and tyrosinase-related protein 1 (TRP1), along with their transcriptional regulator, microphthalmia-associated transcription factor (MITF). SHQA also suppressed α-MSH-induced cellular production of cyclic adenosine monophosphate (cAMP), which inhibited protein kinase A (PKA)-dependent cAMP-responsive element-binding protein (CREB) activation. Docking simulation data showed a potential binding affinity of SHQA to the regulatory subunit RIIβ of PKA, which may also adversely affect PKA and CREB activation. Moreover, SHQA activated ERK1/2 signaling in B16F10 cells, stimulating the proteasomal degradation of MITF. These data suggest that SHQA ameliorated hyperpigmentation in α-MSH-stimulated B16F10 cells by downregulating MITF via PKA inactivation and ERK1/2 phosphorylation, indicating that SHQA is a potent therapeutic agent against skin hyperpigmentation disorders.https://www.mdpi.com/2304-8158/10/10/2254cAMPERKhyperpigmentationmelaninMITFsargahydroquinoic acid |
| spellingShingle | Mohammed Shariful Azam Jae-Il Kim Chang Geun Choi Jinkyung Choi Bonggi Lee Hyeung-Rak Kim Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells Foods cAMP ERK hyperpigmentation melanin MITF sargahydroquinoic acid |
| title | Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells |
| title_full | Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells |
| title_fullStr | Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells |
| title_full_unstemmed | Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells |
| title_short | Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells |
| title_sort | sargahydroquinoic acid suppresses hyperpigmentation by camp and erk1 2 mediated downregulation of mitf in α msh stimulated b16f10 cells |
| topic | cAMP ERK hyperpigmentation melanin MITF sargahydroquinoic acid |
| url | https://www.mdpi.com/2304-8158/10/10/2254 |
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