Objective: To investigate the effect and mechanism of psoralen on melanin content and tyrosinase activity in A375 cells. Method: Cells were inoculated in 6-well plates at a cell density of 2×105 cells and then divided into blank group

estradiol group

psoralen group

psoralen+estrogen receptor(ER) receptor blocker group (ICI182780)

with the concentrations of 1×10-3

1

1 μmol·L-1

respectively. The melanin content and tyrosinase activity were detected by NaOH lysis method and dopaquinone oxidation method; Western blot and real-time fluorescent quantitative PCR assays were used to determine key protein kinases p38

c-Jun N-terminal kinase(JNK)

extracellular signal-regulated kinase 2 (ERK2) and ocular hypotrophy-associated transcription factors (MITF) in the ER/mitogen-activated protein kinase(MAPK) pathway. The protein contents and corresponding mRNA expressions of tyrosinase (TYR)

tyrosinase-associated protein-1 (TRP-1)

and tyrosinase-associated protein-2 (TRP-2) were measured by dopa oxidation. Result: Compared with the blank group

the psoralen group had a significant inhibitory effect on melanin synthesis and TYR activity in A375 cells(P<0.01)

with a significant inhibitory effect on the expression of estrogen receptor β(ERβ) protein in A375 cells (P<0.05)

p38 MAPK

ERK and JNK protein expressions (P<0.01)

protein expressions of MITF

TYR

TRP-1

and TRP-2 (P<0.01)

and ERK2

p38 MAPK

MITF and TRP-1 mRNA expressions (P<0.01); compared with psoralen group

ICI182780 reversed the protein expressions of ERβ

ERK

MITF

TYR

TRP-1 (P<0.01) and the protein expressions of p38

JNK

and TRP-2 (P<0.05); at the same time

it can significantly block psoralen on ERK2

p38

MITF

TRP-1 mRNA expressions (P<0.01). Conclusion: Psoralen down-regulates the expressions of MITF and TYR

TRP-1

and TRP-2 through ER/MAPK signaling pathway

so as to reduce melanin synthesis.