Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: Role of MAPK and Akt pathways.

ETHNOPHARMACOLOGICAL RELEVANCE

In hyperpigmentation disorders marked by melanin overproduction in the skin, including melisma and freckles, melanogenesis is caused by tyrosinase overexpression. Natural medicinal resources, like Phyla nodiflora, a traditional Chinese herbal medicine, have been used for a long time to management of dermatological conditions, such as skin inflammation and melanogenesis. Eupafolin, a functional flavonoid isolated from Phyla nodiflora, is an herbal tea constituent and possesses anti-inflammatory and anticancer activities. However, molecular mechanisms of eupafolin-mediated antimelanogenesis remain unknown. We thus focused on its antimelanogenesis effects in B16F10 mouse melanoma cells.

MATERIAL AND METHODS

B16F10 cells were treated with eupafolin (0.01, 0.1, 1, and 10μM) in a dose-escalation-dependent manner for the determination of melanin, tyrosinase activity and melanogenesis protein levels by ELISA or western blot analysis.

RESULTS

Eupafolin treatment significantly reduced cellular melanin content and tyrosinase activity in a dose-dependent manner (P<0.05), and no cytotoxic effects were observed. Eupafolin was associated with reduction in the levels of phospho-cAMP response element-binding protein and microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase synthesis and tyrosinase-related protein expression, leading to inhibit melanin production. In addition, eupafolin significantly induced the phosphorylation of ERK1/2 and p38 MAPK, whereas the decreased effect was observed in the phosphorylation of Akt. Moreover, inhibitors of these signals recovered or attenuated the inhibitory effects of eupafolin on melanogenesis.

CONCLUSIONS

Our results seem that inhibition of Akt and activation of phospho-ERK or p38 MAPK may lead to the suppression of melanogenesis in eupafolin-treated B16F10 mouse melanoma cells.