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Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: Role of MAPK and Akt pathways.
J Ethnopharmacol 2014; 151(1):386-93JE

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.

Authors+Show Affiliations

Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan.; China Medical University, Taichung, Taiwan.Department of Pediatrics, Division of Neonatology and Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin, Taiwan.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.Department of Respiratory Care, Chang Gung University of Science and Technology, Chia-Yi, Taiwan.Department of Pharmacy, College of Pharmacy & Health Care, Tajen University, Taiwan.Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: flyen@kmu.edu.tw.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24212072

Citation

Ko, Horng-Huey, et al. "Eupafolin, a Skin Whitening Flavonoid Isolated From Phyla Nodiflora, Downregulated Melanogenesis: Role of MAPK and Akt Pathways." Journal of Ethnopharmacology, vol. 151, no. 1, 2014, pp. 386-93.
Ko HH, Chiang YC, Tsai MH, et al. Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: Role of MAPK and Akt pathways. J Ethnopharmacol. 2014;151(1):386-93.
Ko, H. H., Chiang, Y. C., Tsai, M. H., Liang, C. J., Hsu, L. F., Li, S. Y., ... Lee, C. W. (2014). Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: Role of MAPK and Akt pathways. Journal of Ethnopharmacology, 151(1), pp. 386-93. doi:10.1016/j.jep.2013.10.054.
Ko HH, et al. Eupafolin, a Skin Whitening Flavonoid Isolated From Phyla Nodiflora, Downregulated Melanogenesis: Role of MAPK and Akt Pathways. J Ethnopharmacol. 2014;151(1):386-93. PubMed PMID: 24212072.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: Role of MAPK and Akt pathways. AU - Ko,Horng-Huey, AU - Chiang,Yao-Chang, AU - Tsai,Ming-Horng, AU - Liang,Chan-Jung, AU - Hsu,Lee-Fen, AU - Li,Shu-Yu, AU - Wang,Moo-Chin, AU - Yen,Feng-Lin, AU - Lee,Chiang-Wen, Y1 - 2013/11/07/ PY - 2013/09/04/received PY - 2013/10/22/revised PY - 2013/10/23/accepted PY - 2013/11/12/entrez PY - 2013/11/12/pubmed PY - 2014/9/10/medline KW - Eupafolin KW - Melanogenesis KW - Microphthalmia-associated transcription factor KW - Tyrosinase SP - 386 EP - 93 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 151 IS - 1 N2 - 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. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/24212072/Eupafolin_a_skin_whitening_flavonoid_isolated_from_Phyla_nodiflora_downregulated_melanogenesis:_Role_of_MAPK_and_Akt_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(13)00779-4 DB - PRIME DP - Unbound Medicine ER -