Cardamonin suppresses melanogenesis by inhibition of Wnt/β-catenin signaling

Wnt/β-catenin signaling plays important roles in many developmental processes, including neural crest-derived melanocyte development. Here we show that cardamonin, a calchone from Aplinia katsumadai Hayata, inhibited pigmentation in melanocytes through suppression of Wnt/β-catenin signaling pathway. Cardamonin significantly suppressed the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, which are melanocyte differentiation-associated markers, in human normal melanocytes, thereby decreasing intracellular melanin production. In addition, cardamonin promoted the degradation of intracellular β-catenin that was accumulated by Wnt3a-conditioned medium (Wnt3a CM) or bromoindirubin-3′-oxime (BIO), a glycogen synthase kinase-3β (GSK-3β) inhibitor, in HEK293 reporter cells and human normal melanocytes. Our findings indicate that cardamonin may be a potential whitening agent for use in cosmetics and in the medical treatment of hyperpigmentation disorders.