title: Inhibitory Effect of Dried Pomegranate Concentration Powder on Melanogenesis in B16F10 Melanoma Cells; Involvement of p38 and PKA Signaling Pathways.
abstract: Plants rich in antioxidant substances may be useful for preventing skin aging. Pomegranates, containing flavonoids and other polyphenolic compounds, are widely consumed due to their beneficial properties. We examined the underlying mechanisms of dried pomegranate concentrate powder (PCP) on melanin synthesis in B16F10 melanoma cells. The antioxidant effects of PCP were determined by measuring free radical scavenging capacity and transcript levels of antioxidant enzymes. To explore the inhibitory effects of PCP on melanin synthesis, we measured tyrosinase activity and melanin content in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. In addition, the levels of tyrosinase-related protein-1 (TRP-1), TRP-2, tyrosinase, and microphthalmia-associated transcription factor (MITF) expression were determined by Western blotting. Changes in the phosphorylation status of protein kinase A (PKA), cAMP response element-binding protein (CREB), mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase Akt, and glycogen kinase 3β (GSK3β) were also examined. The free radical scavenging activity of PCP increased in a dose-dependent manner. In PCP-treated B16F10 cells, transcript levels of glutathione peroxidase-1 (GPx-1) were increased compared with α-MSH-stimulated cells. In addition, PCP led to the down-regulation of phospho-p38, phospho-PKA, phospho-CREB, phospho-GSK3β, MITF, and TRP-1 compared with α-MSH-stimulated B16F10 cells. We believe this effect may be associated with PCP activity, which leads to the inhibition of melanin production and tyrosinase activity. These results suggest that PCP decreases tyrosinase activity and melanin production via inactivation of the p38 and PKA signaling pathways, and subsequently decreases phosphorylation of CREB, MITF, and melanogenic enzymes. These observations provided new insights on the molecular mechanisms of the skin-whitening property of PCP.
authors.affiliation: The Medical Research Center for Globalization of Herbal Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. vegonia1@hanmail.net.|Department of Preventive Medicine, College of Korean Medicine, Deagu Haany University, Gyeongsan 712-715, Korea. vegonia1@hanmail.net.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Research Institute, Health-Love Co., Ltd., Anyang 431-060, Korea. brchoi@health-love.com.
authors.forename: Beom Rak
authors.initials: BR
authors.lastname: Choi
authors.affiliation: The Medical Research Center for Globalization of Herbal Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. kkong0305@hanmail.net.|Department of Preventive Medicine, College of Korean Medicine, Deagu Haany University, Gyeongsan 712-715, Korea. kkong0305@hanmail.net.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Research Institute, Health-Love Co., Ltd., Anyang 431-060, Korea. key7413@health-love.com.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Research Institute, Health-Love Co., Ltd., Anyang 431-060, Korea. Leehaeyun@health-love.com.
authors.forename: Hae Yeon
authors.initials: HY
authors.lastname: Yi
authors.affiliation: Research Institute, Health-Love Co., Ltd., Anyang 431-060, Korea. hrpark@health-love.com.
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Park
authors.affiliation: The Medical Research Center for Globalization of Herbal Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. dvmsong@hotmail.com.|Department of Histology and Anatomy, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. dvmsong@hotmail.com.
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Song
authors.affiliation: The Medical Research Center for Globalization of Herbal Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. gksxntk@dhu.ac.kr.|Department of Preventive Medicine, College of Korean Medicine, Deagu Haany University, Gyeongsan 712-715, Korea. gksxntk@dhu.ac.kr.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: The Medical Research Center for Globalization of Herbal Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. gucci200@hanmail.net.|Department of Histology and Anatomy, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, Korea. gucci200@hanmail.net.
authors.forename: Sae Kwang
authors.initials: SK
authors.lastname: Ku
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005612:Freeze Drying; D005979:Glutathione Peroxidase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D029561:Lythraceae / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D028321:Plant Preparations / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000521:alpha-MSH / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D028321:Plant Preparations; D000521:alpha-MSH; D005979:Glutathione Peroxidase; D014442:Monophenol Monooxygenase; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D058539:Phosphatidylinositol 3-Kinase; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D000094765:Glutathione Peroxidase GPX1
keywords: anti-melanin; p38; pomegranate concentrate powder; whitening