Anti-Melanogenic Activities of Ranunculus chinensis Bunge via ERK1/2-Mediated MITF Downregulation

Min-Jin Kim; Yong Tae Jeong; Buyng Su Hwang; Yong Hwang; Dae Won Jeong; Yeong Taek Oh

doi:10.7732/kjpr.2022.35.6.704

All Issue

2022 Vol.35, Issue 6 Preview Page Next Page

Research Article

Anti-Melanogenic Activities of Ranunculus chinensis Bunge via ERK1/2-Mediated MITF Downregulation

30 December 2022. pp. 704-712

PDF XML

Abstract

Research on whitening materials using natural alternatives is actively being conducted. The aim of this study was to investigate the in vitro inhibitory effects of Ranunculus chinensis Bunge (RCB) on melanogenesis and associated enzymes, such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 in B16F10 murine melanoma cells. We found that RCB extract significantly attenuated melanin synthesis and reduced the activity of intracellular tyrosinase, a rate-limiting melanogenic enzyme. Western blot analysis showed that RCB extract decreased the protein expression of tyrosinase and TRP-1. In addition, it significantly decreased the expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanogenesis. Extracellular signal-regulated kinase (ERK) activation has been reported to be involved in the inhibition of melanogenesis. Thus, we investigated whether the hypopigmentary effects of RCB extract were related to the activation of ERK. RCB extract induced ERK phosphorylation in a dose-dependent manner. Furthermore, it markedly inhibited body pigmentation in a zebrafish model. Our results suggest that RCB extract inhibits melanogenesis by activating ERK pathway-mediated suppression of MITF and its downstream target genes, including tyrosinase. Therefore, RCB extract can be used as a whitening agent in the development of functional cosmetics.

키워드

B16F10 melanoma cell

Melanin

MITF

Tyrosinase

Whitening

References

Busca, R. and R. Ballotti. 2000. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res. 13:60-69. 10.1034/j.1600-0749.2000.130203.x10841026

Busca, R., C. Bertolotto, J.P. Ortonne and R. Ballotti. 1996. Inhibition of the phosphatidylinositol 3-kinase/p70(S6)- kinase pathway induces B16 melanoma cell differentiation. J. Biol Chem. 271:31824-31830. 10.1074/jbc.271.50.318248943224

Chang, C.J., C.S. Lin, C.C Lu, J. Martel, Y.F. Ko, D.M. Ojcius, S.F. Tseng, T.R. Wu, Y.M. Chen, J.D. Young and H.C. Lai. 2015. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat. Commun. 23:7489. 10.1038/ncomms848926102296PMC4557287

Gunia-Krzyżak, A., J. Popiol and H. Marona. 2016. Melanogenesis inhibitors: strategies for searching for and evaluation of active compounds. Curr. Med. Chem. 23:3548-3574. 10.2174/092986732366616062709493827356545

Hosoi, J., E. Abe, T. Suda and T. Kuroki. 1985. Regulation of melanin synthesis of B16 mouse melanoma cells by 1α,25- dihydroxyvitamin D3 and retinoic acid. Cancer. Res. 45: 1474-1478.

Hwang, E.S., T.H. Lee, W.J. Lee, W.S. Shim, E.J. Yeo, S.H. Kim and S.Y. Kim. 2016. A novel synthetic piper amide derivative NED-180 inhibits hyperpigmentation by activating the PI3K and ERK pathways and by regulating Ca2+ influx via TRPM1 channels. Pigment. Cell Melanoma. Res. 29:81- 91. 10.1111/pcmr.1243026459162

Hyun, H.B., H.J. Hyeon, S.C. Kim, B.R. Go, S.A. Yoon, Y,H Jung and Y.M. Ham. 2021. Anti-melanogenesis effects of Schizophragma hydrangeoides leaf ethanol extracts via downregulation of tyrosinase activity. Korean J. Plant Res. 34:510-516.

Ivanova, D., D. Gerova, T. Chervenkov and T. Yankova. 2005. Polyphenols and antioxidant capacity of bulgarian medicinal plants. J. Ethnopharmacol. 96:145-150. 10.1016/j.jep.2004.08.03315588663

Jinpeng, L., S. Jiang, Y. Yang, X. Zhang, R. Gao, Y. Cao and G. Song. 2020. FGIN-1-27 inhibits melanogenesis by regulating protein kinase A/cAMP-responsive element-binding, protein Kinase C-β, and mitogen-activated protein kinase pathways. Front. Pharmacol. 11: 602889. 10.3389/fphar.2020.60288933390991PMC7775666

Lee, D.Y., J.S. Lee, Y.T. Jeong, G.H. Byun and J.H. Kim. 2017. Melanogenesis inhibition activity of floralginsenoside a from Panax ginseng berry. J. Gingeng Res. 41:602-607. 10.1016/j.jgr.2017.03.00529021710PMC5628341

Levy, C., M. Khaled and D.E Fisher. 2006. MITF: master regulator of melanocyte development and melanoma oncogene. Trends. Mol. Med. 12:406-414. 10.1016/j.molmed.2006.07.00816899407

MacRae, C.A. and R.T Peterson. 2015. Zebrafish as tools for drug discovery. Nat. Rev. Drug Discov. 14:721-731. 10.1038/nrd462726361349

Mas, J.S., I. Gerritsen, C. Hahmann, C. Jimenez-Cervantes and J.C. Garcia-Borron. 2003. Rate limiting factors in melanocortin 1 receptor signalling through the cAMP pathway. Pigment. Cell Res. 16:540-547. 10.1034/j.1600-0749.2003.00073.x12950734

Nigel, W. and Y.E. Feng. 1998. A Practical Dictionary of Chinese Medicine (English and Chinese edition). Subsequent edition, Paradigm Pubns, NM (USA).

Ohguchi, K., Y. Akao and Y. Nozawa. 2006. Stimulation of melanogenesis by the citrus flavonoid naringenin in mouse B16 melanoma cells. Biosci. Biotechnol. Biochem. 70:1499- 1501. 10.1271/bbb.5063516794334

Park, J.U., S.Y. Yang, R.H. Guo, H.X. Li, Y.H. Kim and Y.R. Kim. 2020. Anti-melanogenic effect of Dendropanax morbiferus and its active components via protein kinase A/cyclic adenosine monophosphate-responsive binding protein- and p38 mitogen-activated protein kinase-mediated microphthalmia-associated transcription factor downregulation. Front. Pharmacol. 11:507. 10.3389/fphar.2020.0050732390848PMC7191003

Price, E.R., H.F. Ding, T. Badalian, S. Bhattacharya, C. Takemoto, T.P. Yao, T.J. Hemesath and D.E. Fisher. 1998. Lineage-specific signaling in melanocytes. C-kit stimulation recruits p300/CBP to microphthalmia. J. Biol. Chem. 273: 17983-17986. 10.1074/jbc.273.29.179839660747

Qiyun, W., A.H.Y. Fung., M.L. Xu, K. Poon, E.Y.L. Liu, X.P. Kong, P. Yao, Q.P. Xiong, T.T.X. Dong and K.W.K. Tsim. 2018. Microphthalmia-associated transcription factor up- regulates acetylcholinesterase expression during melanogenesis of murine melanoma cells. J. Biol. Chem. 293: 14417-14428. 10.1074/jbc.RA118.00372930076217PMC6139571

Rannekamp, A.J. and R.T Peterson. 2015. 15 years of zebrafish chemical screening. Curr. Opin. Chem. Biol. 24:58-70. 10.1016/j.cbpa.2014.10.02525461724PMC4339096

Shibahara, S., K. Yasumoto, S. Amae, T. Udono, K. Watanabe, H. Saito and K. Takeda. 2000. Regulation of pigment cell- specific gene expression by MITF. Pigment Cell Res. 13: 98-102. 10.1034/j.1600-0749.13.s8.18.x11041365

Shin, Y.J., C.S. Han, C.S. Lee, H.S. Kim, S.H. Ko, S.K. Hwang, S.G. Ko, J.W. Shin, S.K. Ye and M.H. Chung. 2010. Zeolite 4A, a synthetic Silicate, suppresses melanogenesis through the degradation of microphthalmia-associated transcription factor by extracellular signal-regulated kinase activation in B16F10 melanoma cells. Biol. Pharm. Bull. 33:72-76. 10.1248/bpb.33.7220045939

Solano, F. 2014. Melanins: skin pigments and much more - types, structural models, biological functions, and formation routes. New J. Sci. 2014:28. 10.1155/2014/498276

Solano, F., S. Briganti, M. Picardo and G. Ghanem. 2006. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res. 19:550-571. 10.1111/j.1600-0749.2006.00334.x17083484

Sugumaran, M. 2016. Reactivities of quinone methides versus o-quinones in catecholamine metabolism and eumelanin biosynthesis. Int. J. Mol. Sci. 17:1576. 10.3390/ijms1709157627657049PMC5037842

Sun, L.J., C. Guo, L. Yan, H. Li, J. Sun, X. Huo, X. Xie and J. Hu1. 2020. Syntenin regulates melanogenesis via the p38 MAPK pathway. Mol. Med. Rep. 22:733-738. 10.3892/mmr.2020.1113932626944PMC7339447

Videira, I.F., D.F. Moura and S. Magina. 2013. Mechanisms regulating melanogenesis. An Bras. Dermatol. 88:76-83. 10.1590/S0365-0596201300010000923539007PMC3699939

Vontzalidou, A., G. Zoidis, E. Chaita, M. Makropoulou, N. Aligiannis, G. Lambrinidis, E. Mikros and A.L. Skaltsounis. 2012. Design, synthesis and molecular studies of dihydrostilbene derivatives as potent tyrosinase inhibitors. Bioorg. Med. Chem. Lett. 22:5523-5526. 10.1016/j.bmcl.2012.07.02922835872

Whitney, P.B. and S. Pugliese. 2014. Cosmetic benefits of natural ingredients. J. Drugs Dermatol. 13:1021-1025.

Yaar, M., C. Wu, H.Y. Park, L. Panova, G. Schutz and B.A. Gilchrest. 2006. Bone morphogenetic protein-4, a novel modulator of melanogenesis. J. Biol. Chem. 281:25307-25314. 10.1074/jbc.M60058020016837459

Yuma, W., K. Ogino and H. Hirata. 2019. Swimming capability of zebrafish is governed by water temperature, caudal fin length and genetic background. Sci. Rep. 9:16307. 10.1038/s41598-019-52592-w31704960PMC6841939

Information

Publisher :The Plant Resources Society of Korea
Publisher(Ko) :한국자원식물학회
Journal Title :Korean Journal of Plant Resources
Journal Title(Ko) :한국자원식물학회지
Volume : 35
No :6
Pages :704-712
Received Date : 2022-09-01
Revised Date : 2022-10-05
Accepted Date : 2022-10-11
DOI :https://doi.org/10.7732/kjpr.2022.35.6.704

Korean Journal of Plant Resources ISSN:1226-3591(Print) 2287-8203(Online) 한국자원식물학회지

All Issue