title: Depigmenting action of platycodin D depends on the cAMP/Rho-dependent signalling pathway.
abstract: The 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.
authors: Biospectrum Life Science Institute, Seongnam City, Gyunggi Do, Korea             Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea.
authors: Eunsun
authors: E
authors: Jung
authors: Wangtaek
authors: W
authors: Hwang
authors: Seungbeom
authors: S
authors: Kim
authors: Young-Soo
authors: YS
authors: Kim
authors: Yeong-Shik
authors: YS
authors: Kim
authors: Jongsung
authors: J
authors: Lee
authors: Deokhoon
authors: D
authors: Park
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001905:Botulinum Toxins / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects; D000078404:Epidermal Cells; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012880:Skin Pigmentation / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D000577:Amides; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C497234:MITF protein, human; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; D011725:Pyridines; D012503:Saponins; D014315:Triterpenes; C108830:Y 27632; C108953:platycodin D; D000242:Cyclic AMP; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D054460:rho-Associated Kinases; D001905:Botulinum Toxins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase