Jatropholone B from Jatropha curcas inhibits melanin synthesisextracellular signal-regulated kinase activation in Mel-Ab cell.

Objective: In the present study, we investigated the effects of jatropholone B from Jatropha curcas (J. curcas) on melanin synthesis in Mel-Ab cells.

Methods: Mel-Ab cells were cultured to measure melanin content and tyrosinase activities. Western blotting was performed to investigate jatropholone B-induced signal transduction and measure the expression of melanogenic proteins.

Results: Jatropholone B decreased melanin synthesis in a concentration-dependent manner but did not directly inhibit the activity of tyrosinase, a melanogenic enzyme. Instead, jatropholone B downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase protein levels. Therefore, we investigated jatropholone B-induced signal transduction related to MITF and tyrosinase expression. However, jatropholone B had no significant effect on Akt and glycogen synthase kinase-3β phosphorylation as well as β-catenin change. In contrast, jatropholone B was observed to phosphorylate extracellular signal-regulated kinase (ERK) for the first time. To clarify the involvement of ERK activation in jatropholone B-induced hypopigmentation, we pretreated cells with PD98059, a specific ERK pathway inhibitor, and measured MITF and tyrosinase levels as well as melanin content. PD98059 pretreatment abrogated jatropholone B-induced downregulation of MITF and tyrosinase expression as well as reduction in melanin production.

Conclusions: Based on these results, we suggest that ERK activation by jatropholone B inhibits melanogenesis via the downregulation of MITF and tyrosinase expression. Therefore, jatropholone B from J. curcas can be a candidate for developing a new skin-whitening agent.