4--7-8-trihydroxyisoflavone and kojic-acid

In this study we investigated the inhibitory effects and possible mechanisms of action of 8'-hydroxydaidzein and 3'-hydroxydaidzein, two ortho-dihydroxyisoflavone derivatives from Korean fermented soybean paste, on melanogenesis in B16 murine melanoma cells. The two hydroxydaidzeins reduced melanin synthesis comparably to treatment with kojic acid, a proven whitening agent, in B16 melanoma cells. Furthermore, when in vitro human skin equivalents were treated with the hydroxydaidzeins, the levels of melanogenesis were significantly reduced relative to a kojic acid control. The RT-PCR results demonstrated that depigmentation was due to transcriptional repression of several melanogenesis genes, including microphthalmia-associated transcription factor (MITF), by the hydroxydaidzeins. The immunoblotting results confirmed that diminution of MITF expression subsequently decreased expression of tyrosinase, and tyrosinase-related proteins 1 and 2. Cumulatively, these results suggest that hydroxydaidzeins would be potent attenuators of melanin synthesis as well as effective inhibitors of hyperpigmentation in human skin.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Proliferation; Cell Survival; Enzyme Activation; Fermentation; Gene Expression Regulation, Neoplastic; Glycine max; Humans; Hyperpigmentation; Isoflavones; Melanins; Melanoma, Experimental; Mice; Microphthalmia-Associated Transcription Factor; Oxidoreductases; Pyrones; Reverse Transcriptase Polymerase Chain Reaction; Skin; Transcription, Genetic