AUTHOR=Hong Chen , Yang Lili , Zhang Yifan , Li Yiming , Wu Huali 

TITLE=Epimedium brevicornum Maxim. Extract exhibits pigmentation by melanin biosynthesis and melanosome biogenesis/transfer

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.963160

DOI=10.3389/fphar.2022.963160

ISSN=1663-9812

ABSTRACT=Epimedium brevicornu Maxim. (Epimedii Folium) is a traditional medicine widely utilized in China for sexual dysfunction and osteoporosis treatment. Recently studies have reported that Epimedium flavonoid icariin displayed hair growth and melanogenic ability by targeting tyrosinase activity. Nevertheless, icariin hydrolysate icariside II and icaritin exert depigmentation due to its tyrosinase inhibition. These pigment functional discrepancies from Epimedium constituents arouse our great interest. Then, this study focused on the pigmentation effects of Epimedii Folium extract (EFE) on melanin synthesis and melanosome biogenesis/transfer, and furtherly identifying the bioactive constituents. Firstly, in vitro systemic studies, we discovered that the potent melanogenic and repigmented effects of EFE were dependent on concentration and time manner in multi-melanocytes, normal human skin tissue and vitiligo perilesional areas. In vivo, EFE exhibited repigmented effect on two kinds of depigmented model of N-Phenylthiourea-induced zebrafishes and hydroquinone-induced mice. Mechanistically, EFE strongly promoted tyrosinase activity and upregulated the protein expression of tyrosinase families which finally contributes to melanin biosynthesis by activating MAPK/ERK1/2 signal pathway. Besides, EFE effectively increased melanosome number, accelerated melanosome mature and cytoplasmic transport through the growth/extension of melanocyte dendrite, and induced melanosome transferring from melanocyte to keratinocyte for pigmentation. The six main flavanoid ingredients were identified among EFE. Compared to others, epimedin B (EB) was confirmed as a high-content, low-toxicity and effective melanogenic compound in EFE. Taking together, this study systematically demonstrates the potential pigmentation effect of Epimedium brevicornu Maxim., and clarifies its related molecular mechanisms and melanogenesis basis. These results give additional insight into Epimedium herb pharmacology and may provide a novel therapy basis for hypopigmentation disorders.