title: Ssanghwa-tang, an oriental herbal cocktail, exerts anti-melanogenic activity by suppression of the p38 MAPK and PKA signaling pathways in B16F10 cells.
abstract: BACKGROUND
  Ssanghwa-tang (SHT) is a widely used medication for the treatment of fatigue, pain, inflammation, hypothermia, erectile dysfunction, cancer, and osteoporosis in Asia, however, role of SHT on the melanin synthesis has not been checked previously. Thus, the present study was designed to determine the effect of SHT on α-melanocyte stimulating hormone (α-MSH)-induced melanogensis and its mechanisms of action in murine B16F10 melanoma cells.
  
  
  METHODS
  Cellular melanin content and tyrosinase activity in murine B16F10 melanoma cells were determined after α-MSH stimulation with or without pre-treatment of SHT at the concentration of 250 and 500 μg/ml. Expression level of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB), and mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis.
  
  
  RESULTS
  SHT significantly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of MITF, tyrosinase, and TRP-1. In addition, SHT remarkably suppressed tyrosinase, CRE, and MITF luciferase reporter activity in a resting state as well as in α-MSH-stimulating condition. Phosphorylation of p38 MAPK by α-MSH stimulation was efficiently blocked by SHT pre-treatment. Moreover, SHT as an herbal cocktail showed synergistic anti-melanogenic effect compared with that of each single constituent herb.
  
  
  CONCLUSIONS
  SHT efficiently inhibited c-AMP-induced melanin synthesis in B16F10 cells via suppression of PKA and p38 MAPK signaling pathways and subsequently decreased the level of CREB phosphorylation, MITF, and melanogenic enzymes. These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent.
authors: Korean Medicine (KM)-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine (KIOM), 483 Expo-ro, Yuseong-gu, Daejeon 305-811, Republic of Korea. jyma@kiom.re.kr.
authors: Aeyung
authors: A
authors: Kim
authors: Nam-Hui
authors: NH
authors: Yim
authors: Minju
authors: M
authors: Im
authors: Young Pil
authors: YP
authors: Jung
authors: Chun
authors: C
authors: Liang
authors: Won-Kyung
authors: WK
authors: Cho
authors: Jin Yeul
authors: JY
authors: Ma
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D019426:Integrases / Q000187:drug effects; D008543:Melanins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000187:drug effects; D014442:Monophenol Monooxygenase / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014442:Monophenol Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C045073:Cre recombinase; D019426:Integrases
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