Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways
Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effe...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Journal of Ginseng Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1226845323000556 |
| _version_ | 1797598047576784896 |
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| author | Jianzeng Liu Xiaohao Xu Jingyuan Zhou Guang Sun Zhenzhuo Li Lu Zhai Jing Wang Rui Ma Daqing Zhao Rui Jiang Liwei Sun |
| author_facet | Jianzeng Liu Xiaohao Xu Jingyuan Zhou Guang Sun Zhenzhuo Li Lu Zhai Jing Wang Rui Ma Daqing Zhao Rui Jiang Liwei Sun |
| author_sort | Jianzeng Liu |
| collection | DOAJ |
| description | Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway. |
| first_indexed | 2024-03-11T03:13:52Z |
| format | Article |
| id | doaj.art-d519404899c74fc18021e4581fd2d22c |
| institution | Directory Open Access Journal |
| issn | 1226-8453 |
| language | English |
| last_indexed | 2024-03-11T03:13:52Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Ginseng Research |
| spelling | doaj.art-d519404899c74fc18021e4581fd2d22c2023-11-18T04:28:17ZengElsevierJournal of Ginseng Research1226-84532023-11-01476714725Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathwaysJianzeng Liu0Xiaohao Xu1Jingyuan Zhou2Guang Sun3Zhenzhuo Li4Lu Zhai5Jing Wang6Rui Ma7Daqing Zhao8Rui Jiang9Liwei Sun10Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaNortheast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China; Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China; Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaNortheast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China; Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun, China; Corresponding author. Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, 1478 Gongnong Street, Changchun, Jilin Province, 130021, China.Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China; Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun, China; Corresponding author. Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, 1478 Gongnong Street, Changchun, Jilin Province, 130021, China.Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.http://www.sciencedirect.com/science/article/pii/S1226845323000556P. ginseng phenolic acidsmelanogenesisMITFp-MITFbidirectional regulation |
| spellingShingle | Jianzeng Liu Xiaohao Xu Jingyuan Zhou Guang Sun Zhenzhuo Li Lu Zhai Jing Wang Rui Ma Daqing Zhao Rui Jiang Liwei Sun Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways Journal of Ginseng Research P. ginseng phenolic acids melanogenesis MITF p-MITF bidirectional regulation |
| title | Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways |
| title_full | Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways |
| title_fullStr | Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways |
| title_full_unstemmed | Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways |
| title_short | Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways |
| title_sort | phenolic acids in panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways |
| topic | P. ginseng phenolic acids melanogenesis MITF p-MITF bidirectional regulation |
| url | http://www.sciencedirect.com/science/article/pii/S1226845323000556 |
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