title: Inhibition of the p38 and PKA signaling pathways is associated with the anti-melanogenic activity of Qian-wang-hong-bai-san, a Chinese herbal formula, in B16 cells.
abstract: BACKGROUND
  Qian-wang-hong-bai-san (QW), a Chinese herbal formula, is traditionally used as a skin whitening agent in China.
  
  
  OBJECTIVE
  In our previous screening assays, QW was identified as an effective tyrosinase inhibitor. In this study, we aim to investigate the underlying mechanism of the anti-melanogenic effect of QW in B16 cells.
  
  
  METHODS
  Cytotoxicity of QW in B16 cell line was examined by MTT assay. Cellular tyrosinase activity was determined based on the melanin content measured at 475 nm with a microplate spectrophotometer. Protein expression was analyzed by Western blotting and quantified by Quantity One.
  
  
  RESULTS
  QW dose-dependently inhibited tyrosinase activity and decreased melanin content at 48 h without significant cytotoxicity in B16 cells. Western blot analysis showed that QW treatment down-regulated the expression levels of phospho-p38, phospho-CREB, MITF, tyrosinase, TRP-1 and TRP-2 in a dose-dependent manner. At the same time, QW treatment for 48 h inhibited IBMX-induced elevation of cellular melanin content and tyrosinase activity. However, the attenuation of IBMX-mediated up-regulations of phospho-CREB and phospho-PKA was readily observed with 60 min of QW treatment.
  
  
  CONCLUSIONS
  The anti-melanogenic activity of QW in B16 melanoma cells can be attributed, at least in part, to the inhibition of the p38 MAPK and PKA signaling pathways. These findings shed new light on the molecular mechanisms of the skin-whitening property of QW.
authors: Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors: Ting-Fung
authors: TF
authors: Tsang
authors: Yan
authors: Y
authors: Ye
authors: William Chi-Shing
authors: WC
authors: Tai
authors: Gui-Xin
authors: GX
authors: Chou
authors: Alexander Kai-Man
authors: AK
authors: Leung
authors: Zhi-Ling
authors: ZL
authors: Yu
authors: Wen-Luan Wendy
authors: WL
authors: Hsiao
mesh_terms: D000818:Animals; D057886:Bleaching Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010766:Phosphorylation; D010946:Plants, Medicinal; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D012880:Skin Pigmentation / Q000187:drug effects; D013053:Spectrophotometry; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D057886:Bleaching Agents; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; D008543:Melanins; D047428:Protein Kinase Inhibitors; C574919:qian-wang-hong-bai-san; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase