• Eunsun Jung, Wangtaek Hwang, Seungbeom Kim, Young-Soo Kim, Yeong-Shik Kim, Jongsung Lee, and Deokhoon Park.
• Biospectrum Life Science Institute, Seongnam City, Gyunggi Do, Korea Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea.
• Exp. Dermatol. 2011 Dec 1; 20 (12): 986-91.

AbstractThe overproduction and accumulation of melanin in the skin could lead to a pigmentary disorders, such as melasma, freckle, postinflammatory melanoderma and solar lentigo. Therefore, this study was conducted to investigate the effects of platycodin D (PD) on melanogenesis and its action mechanisms. In this study, we found that PD significantly inhibited melanin synthesis at low concentrations. These effects were further demonstrated by the PD-induced inhibition of cAMP production, phosphorylation of the cAMP-response element-binding protein and expression of microphthalmia-associated transcription factor and its downstream genes, tyrosinase, tyrosinase-related proteins-1 and Dct/tyrosinase-related proteins-2, suggesting that PD inhibits melanogenesis through the downregulation of cAMP signalling. Furthermore, PD induced significant morphological changes in melanocytes, namely, the retraction of dendrites. A small GTPase assays revealed that PD stimulated an increase in GTP-bound Rho content, one of downstream molecules of cAMP, but not in Rac or CDC42 content. Moreover, a Rho inhibitor (C3 exoenzyme) and a Rho kinase inhibitor (Y27632) attenuated the dendrite retraction induced by PD. Taken together, these findings indicate that PD inhibits melanogenesis by inhibiting the cAMP-protein kinase A pathway and also suppresses melanocyte dendricity through activation of the Rho signal that is mediated by PD-induced reduction in cAMP production. Therefore, these results suggest that PD exerts its inhibitory effects on melanogenesis and melanocyte dendricity via suppression of cAMP signalling and may be introduced as an inhibitor of hyperpigmentation caused by UV irradiation or pigmented skin disorders.© 2011 John Wiley & Sons A/S.

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