PMID- 38352950
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240215
IS  - 2214-0883 (Electronic)
IS  - 2095-1779 (Print)
IS  - 2214-0883 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Jan
TI  - Epimedin B exhibits pigmentation by increasing tyrosinase family proteins 
      expression, activity, and stability.
PG  - 69-85
LID - 10.1016/j.jpha.2023.09.006 [doi]
AB  - 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 3beta (GSK3beta)/beta-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.
CI  - (c) 2023 The Authors.
FAU - Hong, Chen
AU  - Hong C
AD  - Department of TCM Chemistry, School of Pharmacy, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, 200000, China.
FAU - Zhang, Yifan
AU  - Zhang Y
AD  - Department of TCM Chemistry, School of Pharmacy, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, 200000, China.
FAU - Yang, Lili
AU  - Yang L
AD  - Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of 
      Traditional Chinese Medicine, Shanghai, 200000, China.
FAU - Xu, Haoyang
AU  - Xu H
AD  - International Education College, Shanghai University of Traditional Chinese 
      Medicine, Shanghai, 200000, China.
FAU - Cheng, Kang
AU  - Cheng K
AD  - Shanghai Inoherb Cosmetics Co., Ltd., Shanghai, 200000, China.
FAU - Lv, Zhi
AU  - Lv Z
AD  - Shanghai Inoherb Cosmetics Co., Ltd., Shanghai, 200000, China.
FAU - Chen, Kaixian
AU  - Chen K
AD  - Department of TCM Chemistry, School of Pharmacy, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, 200000, China.
FAU - Li, Yiming
AU  - Li Y
AD  - Department of TCM Chemistry, School of Pharmacy, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, 200000, China.
FAU - Wu, Huali
AU  - Wu H
AD  - Department of TCM Chemistry, School of Pharmacy, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, 200000, China.
LA  - eng
PT  - Journal Article
DEP - 20230909
PL  - China
TA  - J Pharm Anal
JT  - Journal of pharmaceutical analysis
JID - 101579451
PMC - PMC10859565
OTO - NOTNLM
OT  - Epimedin B
OT  - Melanogenesis
OT  - Melanosome
OT  - Tyrosinase
EDAT- 2024/02/14 06:43
MHDA- 2024/02/14 06:44
PMCR- 2023/09/09
CRDT- 2024/02/14 04:00
PHST- 2023/04/14 00:00 [received]
PHST- 2023/07/28 00:00 [revised]
PHST- 2023/09/05 00:00 [accepted]
PHST- 2024/02/14 06:44 [medline]
PHST- 2024/02/14 06:43 [pubmed]
PHST- 2024/02/14 04:00 [entrez]
PHST- 2023/09/09 00:00 [pmc-release]
AID - S2095-1779(23)00218-6 [pii]
AID - 10.1016/j.jpha.2023.09.006 [doi]
PST - ppublish
SO  - J Pharm Anal. 2024 Jan;14(1):69-85. doi: 10.1016/j.jpha.2023.09.006. Epub 2023 
      Sep 9.