title: Aqueous fraction from Cuscuta japonica seed suppresses melanin synthesis through inhibition of the p38 mitogen-activated protein kinase signaling pathway in B16F10 cells.
abstract: BACKGROUND
  Semen cuscutae has been used traditionally to treat pimples and alleviate freckles and melasma in Korea. The present study aimed to investigate the inhibitory effect of Cuscuta japonica Choisy seeds on alpha-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis.
  
  
  METHODS
  The aqueous fraction from Semen cuscutae (AFSC) was used to determine anti-melanogenic effects by examination of cellular melanin contents, tyrosinase activity assay, cAMP assay and Western blot analysis for melanin synthesis-related signaling proteins in B16F10 mouse melanoma cells.
  
  
  RESULTS
  AFSC markedly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase-related proteins (TRPs). Moreover, AFSC significantly decreased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK) signaling through the down-regulation of α-MSH-induced cAMP. Furthermore, we confirmed that the specific inhibitor of p38 MAPK (SB203580)-mediated suppressed melanin synthesis and tyrosinase activity was further attenuated by AFSC. AFSC also further decreased SB203580-mediated suppression of MITF and TRP expression.
  
  
  CONCLUSIONS
  These results indicate that AFSC inhibits p38 MAPK phosphorylation with suppressed cAMP levels and subsequently down-regulate MITF and TRP expression, which results in a marked reduction of melanin synthesis and tyrosinase activity in α-MSH-stimulated B16F10 cells.
authors.affiliation: Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Jang
authors.forename: Ha Neui
authors.initials: HN
authors.lastname: Kim
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D034182:Cuscuta / Q000737:chemistry; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007093:Imidazoles / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D047428:Protein Kinase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D012639:Seeds; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D000521:alpha-MSH / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007093:Imidazoles; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D000521:alpha-MSH; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580