AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Food Science and Human Wellness Article
PDF (2 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

The mechanisms of melanogenesis inhibition by glabridin: molecular docking, PKA/MITF and MAPK/MITF pathways

Chunxing Pana,1, Xiaoying Liub,1, Yating Zhenga, Zejun Zhanga, Yongliang Lic, Biao Cheb, Guangrong Liub, Lanyue Zhanga, Changzhi Dongd, Haji Akber Aisae, Zhiyun Dua( ), Zhengqiang Yuana( )
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
Infinitus(China) Company Ltd., Guangzhou 510663, China
Foshan Allen Conney Biological Technology Co., Ltd., Foshan 528225, China
Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, France
The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Ürümqi 830011, China

1 These authors contributed equally to this work.Peer review under responsibility of KeAi Communications Co., Ltd.]]>

Show Author Information

Abstract

Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins. However, the underlying mechanism(s) remain not completely understood. The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well. Molecular docking simulations revealed that between catalytic core residues and the compound. The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), TYR-related protein-1 (TRP-1) and TRP-2 in B16 cells. Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells. Also in vivo glabridin therapy significantly reduced hyperpigmentation, epidermal thickening, roughness and inflammation induced by frequent UVA exposure in mice skins, thus beneficial for skin healthcare. These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin, rationalizing the application of the natural compound for skin healthcare.

Keywords

Molecular dockingGlabridinMelanogenesisPKA/MITF pathwayMAPK/ MITF pathway

References

[1]

K.U. Schallreuter, S. Kothari, B. Chavan, et al., Regulation of melanogenesis--controversies and new concepts, Exp. Dermatol. 17 (2008) 395-404. https://doi.org/10.1111/j.1600-0625.2007.00675.x.
Crossref Google Scholar
[2]

T. Kobayashi, K. Urabe, A. Winder, et al., Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis, Embo. J. 13 (1994) 5818-5825.
Crossref Google Scholar
[3]

Y.M. Yang, Y.O. Son, S.A. Lee, et al., Quercetin inhibits α-MSH-stimulated melanogenesis in B16F10 melanoma cells, Phytother. Res. 25 (2011) 1166-1173. https://doi.org/10.1002/ptr.3417.
Crossref Google Scholar
[4]

M. Tachibana, MITF: a stream flowing for pigment cells, Pigment. Cell Res. 13 (2000) 230-240. https://doi.org/10.1034/j.1600-0749.2000.130404.x.
Crossref Google Scholar
[5]

P.A. Insel, H.R. Bourne, P. Coffino, et al., Cyclic AMP-dependent protein kinase: pivotal role in regulation of enzyme induction and growth, Science 190 (1975) 896-898. https://doi.org/10.1126/science.171770.
Crossref Google Scholar
[6]

R. Buscà, R. Ballotti, Cyclic AMP a key messenger in the regulation of skin pigmentation, Pigment. Cell Res. 13 (2000) 60-69. https://doi.org/10.1034/j.1600-0749.2000.130203.x.
Crossref Google Scholar
[7]

H.Y. Peng, C.C. Lin, H.Y. Wang, et al., The melanogenesis alteration effects of Achillea millefolium L. essential oil and linalyl acetate: involvement of oxidative stress and the JNK and ERK signaling pathways in melanoma cells, PLoS ONE. 9 (2014) e95186. https://doi.org/10.1371/journal.pone.0095186.
Crossref Google Scholar
[8]

S.J. Kang, B.R. Choi, E.K. Lee, et al., Inhibitory effect of dried pomegranate concentration powder on melanogenesis in B16F10 melanoma cells; involvement of p38 and PKA signaling pathways, Int. J. Mol. Sci. 16 (2015) 24219. https://doi.org/10.3390/ijms161024219.
Crossref Google Scholar
[9]

T. Yokota, H. Nishio, Y. Kubota, et al., The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation, Pigment. Cell Res. 11 (1998) 355-361. https://doi.org/10.1111/j.1600-0749.1998.tb00494.x.
Crossref Google Scholar
[10]

J. Chen, X. Yu, Y. Huang, Inhibitory mechanisms of glabridin on tyrosinase, Spectrochim. Acta A Mol. Biomol. Spectrosc. 168 (2016) 111-117. https://doi.org/10.1016/j.saa.2016.06.008.
Crossref Google Scholar
[11]

J.H. Hong, S.W. Cao, S.J. Xiang, et al., Glycyrrhiza flavonoids and its major component, licochalcone A, inhibit melanogenesis through MAPK/ERK pathway by activating ERK phosphorylation, J. Dermatol. Sci. 91(2) (2018) 222-225. https://doi.org/10.1016/j.jdermsci.2018.04.016.
Crossref Google Scholar
[12]

T. Panichakul, T. Rodboon, P. Suwannalert, et al., Additive effect of a combination of Artocarpus lakoocha and Glycyrrhiza glabra extracts on tyrosinase inhibition in melanoma B16 cells, Pharmaceuticals (Basel) 13(10) (2020) 310. https://doi.org/10.3390/ph13100310.
Crossref Google Scholar
[13]

W. Qian, W. Liu, D. Zhu, et al., Natural skin-whitening compounds for the treatment of melanogenesis (Review), Exp. Ther. Med. 20 (2020) 173-185. https://doi.org/10.3892/etm.2020.8687.
Crossref Google Scholar
[14]

A. Kim, Y. Yang, M.S. Lee, et al., NDRG2 gene expression in B16F10 melanoma cells restrains melanogenesis via inhibition of Mitf expression, Pigment Cell Melanoma. Res. 21 (2008) 653-664. https://doi.org/10.1111/j.1755-148X.2008.00503.x.
Crossref Google Scholar
[15]

S.T. Chou, W.L. Chang, C.T. Chang, et al., Cinnamomum cassia essential oil inhibits α-MSH-induced melanin production and oxidative stress in murine B16 melanoma cells, Int J Mol Sci. 14. (2013) 19186. https://doi.org/10.3390/ijms140919186.
Crossref Google Scholar
[16]

J.W. Lim, J.H. Ha, Y.J. Jeong, et al., Anti-melanogenesis effect of dehydroglyasperin C through the downregulation of MITF via the reduction of intracellular cAMP and acceleration of ERK activation in B16F1 melanoma cells, Pharmacol. Rep. 70 (2018) 930-935. https://doi.org/10.1016/j.pharep.2018.02.024.
Crossref Google Scholar
[17]

A. Kim, N.H. Yim, M. Im, et al., Ssanghwa-tang, an oriental herbal cocktail, exerts anti-melanogenic activity by suppression of the p38 MAPK and PKA signaling pathways in B16F10 cells, BMC Complement. Altern. Med. 13 (2013) 214. https://doi.org/10.1186/1472-6882-13-214.
Crossref Google Scholar
[18]

N. Takahashi, M. Imai, Y. Komori, Inhibitory effects of p-alkylaminophenol on melanogenesis, Bioorg. Med. Chem. 22 (2014) 4677-4683. https://doi.org/10.1016/j.bmc.2014.07.016.
Crossref Google Scholar
[19]

Y.O. Son, S.A. Lee, S.S. Kim, et al., Acteoside inhibits melanogenesis in B16F10 cells through ERK activation and tyrosinase down-regulation, J. Pharm. Pharmacol. 63 (2011) 1309-1319. https://doi.org/10.1111/j.2042-7158.2011.01335.x.
Crossref Google Scholar
[20]

J.H. Kim, A.R. Hong, Y.H. Kim, et al., JNK suppresses melanogenesis by interfering with CREB-regulated transcription coactivator 3-dependent MITF expression, Theranostics. 10 (2020) 4017-4029. https://doi.org/10.7150/thno.41502.
Crossref Google Scholar
[21]

C. Simmler, G.F. Pauli, S.N. Chen, Phytochemistry and biological properties of glabridin, Fitoterapia. 90 (2013) 160-184. https://doi.org/10.1016/j.fitote.2013.07.003.
Crossref Google Scholar
[22]

T. Pillaiyar, M. Manickam, S.H. Jung, Downregulation of melanogenesis: drug discovery and therapeutic options, Drug Discov. Today 22 (2017) 282-298. https://doi.org/10.1016/j.drudis.2016.09.016.
Crossref Google Scholar
[23]

C. Bertolotto, P. Abbe, T.J. Hemesath, et al., Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes, J. Cell Biol. 142 (1998) 827. https://doi.org/10.1083/jcb.142.3.827.
Crossref Google Scholar
[24]

L.T. Ng, L.T. Lin, C.L. Chen, et al., Anti-melanogenic effects of δ-tocotrienol are associated with tyrosinase-related proteins and MAPK signaling pathway in B16 melanoma cells, Phytomedicine 21 (2014) 978-983. https://doi.org/10.1016/j.phymed.2014.03.003.
Crossref Google Scholar
[25]

L. Gu, J. Lu, Q. Li, et al., A network-based analysis of key pharmacological pathways of Andrographis paniculata acting on Alzheimer’s disease and experimental validation, J. Ethnopharmacol. 251 (2020) 112488. https://doi.org/10.1016/j.jep.2019.112488.
Crossref Google Scholar
[26]

W.T. Ismaya, H.J. Rozeboom, A. Weijn, et al., Crystal structure of Agaricus bisporus mushroom tyrosinase: identity of the tetramer subunits and interaction with tropolone, Biochemistry 50(24) (2011) 5477-5786. https://doi.org/10.1021/bi200395t.
Crossref Google Scholar
[27]

S. Momtaz, N. Lall, A. Basson, Inhibitory activities of mushroom tyrosine and DOPA oxidation by plant extracts, S. Afr. J. Bot. 74 (2008) 577-582. https://doi.org/10.1016/j.sajb.2008.02.005.
Crossref Google Scholar
[28]

K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method, Methods 25(4) (2001) 402-408. https://doi.org/10.1006/meth.2001.1262.
Crossref Google Scholar
Food Science and Human Wellness
Volume 12 Issue 1,
January 2023
Pages 212-222
DOI: 10.1016/j.fshw.2022.07.011
Cite this article:
Pan C, Liu X, Zheng Y, et al. The mechanisms of melanogenesis inhibition by glabridin: molecular docking, PKA/MITF and MAPK/MITF pathways. Food Science and Human Wellness, 2023, 12(1): 212-222. https://doi.org/10.1016/j.fshw.2022.07.011

1012

Views

135

Downloads

11

Crossref

11

Web of Science

13

Scopus

1

CSCD

Altmetrics
Received: 24 February 2021
Revised: 05 May 2021
Accepted: 11 June 2021
Published: 09 August 2022
© 2023 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return