punicalagin and Hypopigmentation

Punicalagin is a phenolic compound with antioxidant properties. However, the effects of punicalagin on melanin synthesis have been poorly evaluated. Therefore, we investigated the effects of punicalagin on melanogenesis in Mel-Ab cells. Punicalagin significantly inhibited melanin synthesis in a dose-dependent manner. In accordance with the melanin content, punicalagin also dose-dependently decreased tyrosinase activity. Punicalagin did not directly inhibit tyrosinase in a cell-free system but did downregulate the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. Therefore, we examined the effects of punicalagin on melanogenesis-related signaling pathways. Punicalagin induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation but had no effect on β-catenin level. We measured melanin content and MITF expression in the presence of the ERK pathway inhibitor PD98059 and/or the Akt pathway inhibitor LY294002. Cotreatment with PD98059 and LY294002 almost completely restored punicalagin-induced hypopigmentation. These data indicate that punicalagin inhibits melanin synthesis through ERK and Akt phosphorylation, with subsequent downregulation of MITF and tyrosinase.

Topics: Animals; Antioxidants; Cell Line, Transformed; Chromones; Enzyme Inhibitors; Flavonoids; Hydrolyzable Tannins; Hypopigmentation; Kinetics; MAP Kinase Signaling System; Melanins; Melanocytes; Mice; Microphthalmia-Associated Transcription Factor; Microscopy, Phase-Contrast; Monophenol Monooxygenase; Morpholines; Phosphorylation; Protein Kinase Inhibitors; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt