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

Abstract

Epimedium brevicornum 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 cause depigmentation due to their 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 further identified the bioactive constituents. First, in in vitro systemic studies, we discovered that the potent melanogenic and repigmented effects of EFE were dependent on concentration and amount of time in multi-melanocytes, normal human skin tissue, and vitiligo perilesional areas. In vivo, EFE exhibited repigmented effect on two kinds of depigmented models of N-phenylthiourea-induced zebrafish and hydroquinone-induced mice. Mechanistically, EFE strongly promoted tyrosinase activity and upregulated the protein expression of tyrosinase families which finally contribute to melanin biosynthesis by activating the MAPK/ERK1/2 signal pathway. In addition, EFE effectively increased melanosome number, accelerated melanosome maturity and cytoplasmic transport through the growth/extension of melanocyte dendrites, and induced melanosome transfer from melanocyte to keratinocyte for pigmentation. The six main flavonoid 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 all these together, this study systematically demonstrates the potential pigmentation effect of Epimedium brevicornum 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.

Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity and stability

“…extract were identified by using high-performance liquid chromatography (Figure 1A, B). Comparably, Epimedin B showed the most effect of melanogenesis and tyrosinase activation in five major Epimedium flavonoids (referred to our study) [13]. To verify the melanogenic effect, melanin contents on two melanoma lines (B16F10 cell and MNT-1 cell) from different species were performed with different concentration of EB (25, 50 and 100 μM) for 72 h (cell viability test has been performed in our published study) [13].…”

“…Recently, our study discovered that Epimedin B (EB) (PubChem CID: 5748393), as a high-content, low-toxicity flavonoid compound in Epimedium brevicornum Maxim. extract, strongly exerted melanogenesis and tyrosinase activation effect [13]. However, there are no studies of EB in pigment synthesis and regulation mechanism.…”

Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability

“…S1 ; for more details, refer to our previous study [ 8 ]). To verify the melanogenic effect, the melanin content in both melanoma cell lines (B16F10 cells and MNT-1 cells) obtained from different species was determined by treating with different concentrations of EB (25, 50, and 100 μM) for 72 h (cell viability assay was performed in our previous study [ 8 ]). IBMX, a cAMP-elevating agonist for melanogenesis, and α-MSH were used as a positive control.…”

“…In our previous study, we reported that epimedin B (EB; PubChem CID: 5748393), an abundant, low-toxicity flavonoid ingredient presenting in Epimedium brevicornum Maxim., is a strong inducer of melanogenesis and activator of TYRs [ 8 ]. However, no studies have evaluated the role of EB in melanin pigment synthesis and the mechanism underlying the regulation.…”

Putrescine Upregulates Melanogenesis Through Modulation of MITF Transcription Factor in B16F1 Mouse Melanoma Cells

“…Tyrosinase (TYR), a copper-containing metalloprotein as well as tyrosinase-related protein 1 (TRP-1) and TRP-2 play a crucial role in melanin synthesis ( 10 ). In addition, the microphthalmia-associated transcription factor (MITF) is essential for melanocytes and melanogenesis differentiation by regulating multiple pigmentation-related genes, including TYR, TRP-1 and TRP-2 ( 11 ). However, an increase in hydrogen peroxide leads to a decrease in antioxidant enzymes, including methionine sulfoxide reductase A and B (MSRA and MSRB).…”