title: Andrographolide suppresses melanin synthesis through Akt/GSK3β/β-catenin signal pathway.
abstract: BACKGROUND
  Tyrosinase (TYR) is the key enzyme controlling the production of melanin. Very few papers have reported that andrographolide can inhibit melanin content.
  
  
  OBJECTIVE
  To investigate the effects of andrographolide on melanin synthesis.
  
  
  METHODS
  Cell viability, melanin content, TYR activity, transcriptional and protein expression levels of TYR family and other kinds of proteins involved in melanogenesis were measured after the treatments of andrographolide.
  
  
  RESULTS
  It was found that andrographolide decreased melanin content, TYR activity and transcriptional and protein expression of TYR family and microphthalmia-associated transcription factor (MITF) in B16F10 melanoma cells. Data showed andrographolide also decreased melanin content and TYR content in ultraviolet B (UVB) irradiation induced brown guinea pigs. Moreover, we found that melanin content and TYR activity were effectively inhibited in Human Epidermis Melanocyte (HEM) treated with andrographolide at the medium concentrations without apparent effect on cell viability. Results in experiments treated with MG-132 or cycloheximide (CHX) showed that andrographolide lowered the content of β-catenin in cell nucleus resulting from accelerating the degradation of β-catenin. Phosphorylation of glycogen synthase kinase 3β (GSK3β) and Akt decreased simultaneously. 6-Bromoindirubin-3'-oxime (BIO, inhibitor of GSK3β) and insulin-like growth factors-1 (IGF-1, activator of Akt) could reverse the decline of β-catenin in B16F10 cells induced by andrographolide.
  
  
  CONCLUSIONS
  These results demonstrate that andrographolide can effectively suppress melanin content and TYR activity in B16F10 cells, HEM cells and UVB-induced brown guinea pig skin by decreasing phosphorylation of GSK3β dependent on Akt, promoting the degradation of β-catenin, inhibiting β-catenin into the nucleus and decreasing the expression of MITF and TYR family. Data indicate that andrographolide may be a potential whiting agent which can have great market in cosmetics and in clinical such as curing hyperpigmentation disorders.
authors: Shanghai Key Laboratory of Regulatory Biology, School of Life Science, East China Normal University, China.
authors: Ping-Ya
authors: PY
authors: Zhu
authors: Shanghai Key Laboratory of Regulatory Biology, School of Life Science, East China Normal University, China.
authors: Wei-Han
authors: WH
authors: Yin
authors: Shanghai Key Laboratory of Regulatory Biology, School of Life Science, East China Normal University, China.
authors: Meng-Ran
authors: MR
authors: Wang
authors: Shanghai Key Laboratory of Regulatory Biology, School of Life Science, East China Normal University, China.
authors: Yong-Yan
authors: YY
authors: Dang
authors: Shanghai Key Laboratory of Regulatory Biology, School of Life Science, East China Normal University, China. Electronic address: xyye@bio.ecnu.edu.cn.
authors: Xi-Yun
authors: XY
authors: Ye
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004224:Diterpenes / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006168:Guinea Pigs; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000528:radiation effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014466:Ultraviolet Rays; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D051176:beta Catenin; C030419:andrographolide; D014442:Monophenol Monooxygenase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: Andrographolide; Melanin synthesis; TYR family; β-Catenin