Anti-Melanogenic Activities of Heracleum moellendorffii via ERK1/2-Mediated MITF Downregulation.
In this study, the anti-melanogenic effects ofHeracleum moellendorffiiHance extract (HmHe) and the mechanisms through which it inhibits melanogenesis in melan-a cells were investigated. Mushroom tyrosinase (TYR) activity and melanin content as well as cellular tyrosinase activity were measured in the cells. mRNA and protein expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), TYR-related protein-1 (TYRP-1) and -2 were also examined. The results demonstrate that treatment with HmHe significantly inhibits mushroom tyrosinase activity. Furthermore, HmHe also markedly inhibits melanin production and intracellular tyrosinase activity. By suppressing the expression of TYR, TYRP-1, TYRP-2, and MITF, HmHe treatment antagonized melanin production in melan-a cells. Additionally, HmHe interfered with the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, with reversal of HmHe-induced melanogenesis inhibition after treatment with specific inhibitor U0126. In summary, HmHe can be said to stimulate ERK1/2 phosphorylation and subsequent degradation of MITF, resulting in suppression of melanogenic enzymes and melanin production, possibly due to the presence of polyphenolic compounds.
Department of Food Science & Biotechnology, Kyungpook National University, Daegu 41566, Korea. mbalam@knu.ac.kr.
Md Badrul
MB
Alam
Department of Food Science & Biotechnology, Kyungpook National University, Daegu 41566, Korea. vicpie@knu.ac.kr.
Bum-Ju
BJ
Seo
Department of Food Science & Biotechnology, Kyungpook National University, Daegu 41566, Korea. laputaily@hotmail.com.
Peijun
P
Zhao
Department of Food Science & Biotechnology, Kyungpook National University, Daegu 41566, Korea. sang@knu.ac.kr.
Sang-Han
SH
Lee
D000363:Agaricales / Q000737:chemistry; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation; D030002:Heracleum / Q000737:chemistry*; D007211:Indoles / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction
D002070:Butadienes; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D007211:Indoles; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D009570:Nitriles; D010936:Plant Extracts; D020011:Protective Agents; C113580:U 0126; C009904:melanogen; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D014442:Monophenol Monooxygenase; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase
ERK; Heracleum moellendorffii; MITF; melanin; melanogenesis; tyrosinase