Horng-Huey Ko1, Yao-Chang Chiang2, Ming-Horng Tsai3, Chan-Jung Liang4, Lee-Fen Hsu5, Shu-Yu Li6, Moo-Chin Wang1, Feng-Lin Yen7, Chiang-Wen Lee8. 1. Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan.; China Medical University, Taichung, Taiwan. 3. Department of Pediatrics, Division of Neonatology and Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin, Taiwan. 4. Department of Nutrition and Health Sciences, Chang-Gung Institute of Technology, Taoyuan, Taiwan.; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan. 5. Department of Respiratory Care, Chang Gung University of Science and Technology, Chia-Yi, Taiwan. 6. Department of Pharmacy, College of Pharmacy & Health Care, Tajen University, Taiwan. 7. Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: flyen@kmu.edu.tw. 8. Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi, Taiwan; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan. Electronic address: cwlee@gw.cgust.edu.tw.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: In hyperpigmentation disorders marked by melanin overproduction in the skin, including melisma and freckles, melanogenesis is caused by tyrosinase overexpression. Natural medicinal resources, like Phyla nodiflora, a traditional Chinese herbal medicine, have been used for a long time to management of dermatological conditions, such as skin inflammation and melanogenesis. Eupafolin, a functional flavonoid isolated from Phyla nodiflora, is an herbal tea constituent and possesses anti-inflammatory and anticancer activities. However, molecular mechanisms of eupafolin-mediated antimelanogenesis remain unknown. We thus focused on its antimelanogenesis effects in B16F10 mouse melanoma cells. MATERIAL AND METHODS: B16F10 cells were treated with eupafolin (0.01, 0.1, 1, and 10μM) in a dose-escalation-dependent manner for the determination of melanin, tyrosinase activity and melanogenesis protein levels by ELISA or western blot analysis. RESULTS: Eupafolin treatment significantly reduced cellular melanin content and tyrosinase activity in a dose-dependent manner (P<0.05), and no cytotoxic effects were observed. Eupafolin was associated with reduction in the levels of phospho-cAMP response element-binding protein and microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase synthesis and tyrosinase-related protein expression, leading to inhibit melanin production. In addition, eupafolin significantly induced the phosphorylation of ERK1/2 and p38 MAPK, whereas the decreased effect was observed in the phosphorylation of Akt. Moreover, inhibitors of these signals recovered or attenuated the inhibitory effects of eupafolin on melanogenesis. CONCLUSIONS: Our results seem that inhibition of Akt and activation of phospho-ERK or p38 MAPK may lead to the suppression of melanogenesis in eupafolin-treated B16F10 mouse melanoma cells.
ETHNOPHARMACOLOGICAL RELEVANCE: In hyperpigmentation disorders marked by melanin overproduction in the skin, including melisma and freckles, melanogenesis is caused by tyrosinase overexpression. Natural medicinal resources, like Phyla nodiflora, a traditional Chinese herbal medicine, have been used for a long time to management of dermatological conditions, such as skin inflammation and melanogenesis. Eupafolin, a functional flavonoid isolated from Phyla nodiflora, is an herbal tea constituent and possesses anti-inflammatory and anticancer activities. However, molecular mechanisms of eupafolin-mediated antimelanogenesis remain unknown. We thus focused on its antimelanogenesis effects in B16F10 mousemelanoma cells. MATERIAL AND METHODS: B16F10 cells were treated with eupafolin (0.01, 0.1, 1, and 10μM) in a dose-escalation-dependent manner for the determination of melanin, tyrosinase activity and melanogenesis protein levels by ELISA or western blot analysis. RESULTS:Eupafolin treatment significantly reduced cellular melanin content and tyrosinase activity in a dose-dependent manner (P<0.05), and no cytotoxic effects were observed. Eupafolin was associated with reduction in the levels of phospho-cAMP response element-binding protein and microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase synthesis and tyrosinase-related protein expression, leading to inhibit melanin production. In addition, eupafolin significantly induced the phosphorylation of ERK1/2 and p38 MAPK, whereas the decreased effect was observed in the phosphorylation of Akt. Moreover, inhibitors of these signals recovered or attenuated the inhibitory effects of eupafolin on melanogenesis. CONCLUSIONS: Our results seem that inhibition of Akt and activation of phospho-ERK or p38 MAPK may lead to the suppression of melanogenesis in eupafolin-treated B16F10 mousemelanoma cells.
Authors: Hyun Jung Roh; Hye-Ji Noh; Chun Su Na; Chung Sub Kim; Ki Hyun Kim; Cheol Yi Hong; Kang Ro Lee Journal: Biomol Ther (Seoul) Date: 2015-05-01 Impact factor: 4.634