Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability
Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177923002186 |
| _version_ | 1797334810358710272 |
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| author | Chen Hong Yifan Zhang Lili Yang Haoyang Xu Kang Cheng Zhi Lv Kaixian Chen Yiming Li Huali Wu |
| author_facet | Chen Hong Yifan Zhang Lili Yang Haoyang Xu Kang Cheng Zhi Lv Kaixian Chen Yiming Li Huali Wu |
| author_sort | Chen Hong |
| collection | DOAJ |
| description | Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear. Herein, as an extension to our previous investigation, we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins (TYRs) in terms of expression, activity, and stability. The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt (referred to as protein kinase B (PKB))/glycogen synthase kinase 3β (GSK3β)/β-catenin, p-p70 S6 kinase cascades, and protein 38 (p38)/mitogen-activated protein (MAP) kinase (MAPK) and extracellular regulated protein kinases (ERK)/MAPK pathways, after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues. Furthermore, EB exerted repigmentation by stimulating TYR activity in hydroquinone- and N-phenylthiourea-induced TYR inhibitive models, including melanoma cells, zebrafish, and mice. Finally, EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding, TYR-related protein 1 formation, and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes. These data conclude that EB can target TYRs and alter their expression, activity, and stability, thus stimulating their pigmentation function, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries. |
| first_indexed | 2024-03-08T08:26:36Z |
| format | Article |
| id | doaj.art-94eae75705c549e1bbf8fec16f5765da |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-03-08T08:26:36Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-94eae75705c549e1bbf8fec16f5765da2024-02-02T04:38:52ZengElsevierJournal of Pharmaceutical Analysis2095-17792024-01-011416985Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stabilityChen Hong0Yifan Zhang1Lili Yang2Haoyang Xu3Kang Cheng4Zhi Lv5Kaixian Chen6Yiming Li7Huali Wu8Department of TCM Chemistry, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, ChinaDepartment of TCM Chemistry, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, ChinaDepartment of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, ChinaInternational Education College, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, ChinaShanghai Inoherb Cosmetics Co., Ltd., Shanghai, 200000, ChinaShanghai Inoherb Cosmetics Co., Ltd., Shanghai, 200000, ChinaDepartment of TCM Chemistry, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, ChinaDepartment of TCM Chemistry, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China; Corresponding author.Department of TCM Chemistry, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China; Corresponding author.Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear. Herein, as an extension to our previous investigation, we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins (TYRs) in terms of expression, activity, and stability. The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt (referred to as protein kinase B (PKB))/glycogen synthase kinase 3β (GSK3β)/β-catenin, p-p70 S6 kinase cascades, and protein 38 (p38)/mitogen-activated protein (MAP) kinase (MAPK) and extracellular regulated protein kinases (ERK)/MAPK pathways, after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues. Furthermore, EB exerted repigmentation by stimulating TYR activity in hydroquinone- and N-phenylthiourea-induced TYR inhibitive models, including melanoma cells, zebrafish, and mice. Finally, EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding, TYR-related protein 1 formation, and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes. These data conclude that EB can target TYRs and alter their expression, activity, and stability, thus stimulating their pigmentation function, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.http://www.sciencedirect.com/science/article/pii/S2095177923002186Epimedin BMelanosomeTyrosinaseMelanogenesis |
| spellingShingle | Chen Hong Yifan Zhang Lili Yang Haoyang Xu Kang Cheng Zhi Lv Kaixian Chen Yiming Li Huali Wu Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability Journal of Pharmaceutical Analysis Epimedin B Melanosome Tyrosinase Melanogenesis |
| title | Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability |
| title_full | Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability |
| title_fullStr | Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability |
| title_full_unstemmed | Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability |
| title_short | Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability |
| title_sort | epimedin b exhibits pigmentation by increasing tyrosinase family proteins expression activity and stability |
| topic | Epimedin B Melanosome Tyrosinase Melanogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2095177923002186 |
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