CoChat
Sign Up
Cited by 28melanin and skin pigmentationGinseng Biological Effects and ApplicationsDermatologic Treatments and Research

Anti-melanogenic property of ginsenoside Rf from Panax ginseng via inhibition of CREB/MITF pathway in melanocytes and ex vivo human skin

Open access
Lee, Ha-Ri, Jung, Joon Min, Seo, Ji-Yeon, Chang, Sung Eun, Song, Youngsup·2021·Journal of Ginseng Research
DOI 10.1016/j.jgr.2020.11.003PMC PMC8587488
Open this paper in CoChat — free accountOpen PDF

Abstract

Ginsenosides of Panax ginseng are used to enhance skin health and beauty. The present study aimed to investigate the potential use of ginsenoside Rf (Rf) from Panax ginseng as a new anti-pigmentation agent. The anti-melanogenic effects of Rf were explored. The transcriptional activity of the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and the expression levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related proteins (Tyrps) were evaluated in melanocytes and UV-irradiated ex vivo human skin. Rf significantly inhibited Forskolin (FSK) or UV-stimulated melanogenesis. Consistently, cellular tyrosinase activity and levels of MITF, tyrosinase, and Tyrps were downregulated. Furthermore, Rf suppressed MITF promoter activity, which was stimulated by FSK or CREB-regulated transcription coactivator 3 (CRTC3) overexpression. Increased CREB phosphorylation and protein kinase A (PKA) activity induced by FSK were also mitigated in the presence of Rf. Rf can be used as a reliable anti-pigmentation agent, which has a scientifically confirmed and reproducible action mechanism, via inhibition of CREB/MITF pathway.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.jgr.2020.11.003

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 52

  1. [1]Briganti S. Camera E. Picardo M. Chemical and instrumental approaches to treat hyperpigmentation Pigment Cell Research 16 2003 101 110 12622786
  2. [2]Engasser P.G. Maibach H.I. Cosmetics and dermatology: bleaching creams Journal of the American Academy of Dermatology 5 1981 143 147 7021611
  3. [3]Yamaguchi Y. Hearing V.J. Physiological factors that regulate skin pigmentation Biofactors 35 2009 193 199 19449448 PMC2793097
  4. [4]Slominski A. Tobin D.J. Shibahara S. Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation Physiological Reviews 84 2004 1155 1228 15383650
  5. [5]Bang S. Won K.H. Moon H.R. Yoo H. Hong A. Song Y. Chang S.E. Novel regulation of melanogenesis by adiponectin via the AMPK/CRTC pathway Pigment Cell Melanoma Res 30 2017 553 557 28481450
  6. [6]Kim J.-H. Hong A-r Kim Y.-H. Yoo H. Kang S.-W. Chang S.E. Song Y. JNK suppresses melanogenesis by interfering with CREB-regulated transcription coactivator 3-dependent MITF expression Theranostics 10 2020 4017 32226536 PMC7086364
  7. [7]Kwak Y.-S. Bibliographic consideration on the efficacy and the origin of Korean ginseng Journal of Ginseng Culture 1 2019 43 56
  8. [8]Wei X. Chen J. Su F. Su X. Hu T. Hu S. Stereospecificity of ginsenoside Rg3 in promotion of the immune response to ovalbumin in mice International Immunology 24 2012 465 471 22427454
  9. [9]Joo S.S. Yoo Y.M. Ahn B.W. Nam S.Y. Kim Y.-B. Hwang K.W. Lee D.I. Prevention of inflammation-mediated neurotoxicity by Rg3 and its role in microglial activation Biological and Pharmaceutical Bulletin 31 2008 1392 1396 18591781
  10. [10]Rivera E. Hu S. Concha C. Ginseng and aluminium hydroxide act synergistically as vaccine adjuvants Vaccine 21 2003 1149 1157 12559792
  11. [11]Rivera E. Pettersson F.E. Inganäs M. Paulie S. Grönvik K.-O. The Rb1 fraction of ginseng elicits a balanced Th1 and Th2 immune response Vaccine 23 2005 5411 5419 16286158
  12. [12]So M.W. Lee E.-J. Lee H.S. San Koo B. Kim Y.-G. Lee C.-K. Yoo B. Protective effects of ginsenoside Rg3 on human osteoarthritic chondrocytes Modern Rheumatology 23 2013 104 111 22454193
  13. [13]Wei X. Su F. Su X. Hu T. Hu S. Stereospecific antioxidant effects of ginsenoside Rg3 on oxidative stress induced by cyclophosphamide in mice Fitoterapia 83 2012 636 642 22310172
  14. [14]Jiménez-Pérez Z.E. Kim Y.-J. Castro-Aceituno V. Mathiyalagan R. Markus J. Ahn S. Simu S.Y. Yang D.-C. Novel application of cultured roots of mountain ginseng (Panax ginseng meyer) and ginsenoside re as safe antimelanogenic cosmeceutical components African Journal of Traditional, Complementary and Alternative Medicines 14 2017 209 218
  15. [15]Odashima S. Ohta T. Kohno H. Matsuda T. Kitagawa I. Abe H. Arichi S. Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides Cancer Research 45 1985 2781 2784 3986809
  16. [16]Lee D.Y. Lee J. Jeong Y.T. Byun G.H. Kim J.H. Melanogenesis inhibition activity of floralginsenoside A from Panax ginseng berry Journal of Ginseng Research 41 2017 602 607 29021710 PMC5628341
  17. [17]Lee S.J. Lee W.J. Chang S.E. Lee G.-Y. Antimelanogenic effect of ginsenoside Rg3 through extracellular signal-regulated kinase-mediated inhibition of microphthalmia-associated transcription factor 39 2015 238 242 PMC4506376 26199555
  18. [18]Qin X. Liu Y. Feng Y. Jiang J. Ginsenoside Rf alleviates dysmenorrhea and inflammation through the BDNF-TrkB-CREB pathway in a rat model of endometriosis Food Funct 10 2019 244 249 30547177
  19. [19]Lee H. Gonzalez F.J. Yoon M. Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor alpha Biochem Biophys Res Commun 339 2006 196 203 16297877
  20. [20]Ahn S. Siddiqi M.H. Aceituno V.C. Simu S.Y. Yang D.C. Suppression of MAPKs/NF-kappaB activation induces intestinal anti-inflammatory action of ginsenoside Rf in HT-29 and RAW264.7 cells Immunol Invest 45 2016 439 449 27224660
  21. [21]Kim M.K. Kang H. Baek C.W. Jung Y.H. Woo Y.C. Choi G.J. Shin H.Y. Kim K.S. Antinociceptive and anti-inflammatory effects of ginsenoside Rf in a rat model of incisional pain J Ginseng Res 42 2018 183 191 29719465 PMC5925619
  22. [22]Li Y. Chen C. Li S. Jiang C. Ginsenoside Rf relieves mechanical hypersensitivity, depression-like behavior, and inflammatory reactions in chronic constriction injury rats Phytother Res 33 2019 1095 1103 30740801
  23. [23]Siraj F.M. Natarajan S. Huq M.A. Kim Y.J. Yang D.C. Structural investigation of ginsenoside Rf with PPARγ major transcriptional factor of adipogenesis and its impact on adipocyte Journal of Ginseng Research 39 2015 141 147 26045687 PMC4452529
  24. [24]Chen W. Balan P. Popovich D.G. Analysis of ginsenoside content (Panax ginseng) from different regions Molecules 24 2019 PMC6803836 31561496
  25. [25]Chan T. But P. Cheng S. Kwok I. Lau F. Xu H. Differentiation and authentication of Panax ginseng, Panax quinquefolius, and ginseng products by using HPLC/MS Analytical Chemistry 72 2000 1281 1287 10740871
  26. [26]Minh Nguyen H. Truong Nguyen H. Win N. Piow Wong C. Vu Huynh K.L. Hoang N.N. Do K.M. Thi Nguyen H. Viet Ho D. Duc Nguyen M. Antimelanogenic activity of ocotillol-type saponins from Panax vietnamensis Chem Biodivers 17 2020 e2000037 32163220
  27. [27]Lee D.Y. Kim H.-G. Lee Y.-G. Kim J.H. Lee J.W. Choi B.-R. Jang I.-B. Kim G.-S. Baek N.-I. Isolation and quantification of ginsenoside Rh23, a new anti-melanogenic compound from the leaves of Panax ginseng Molecules 23 2018 267 PMC6017343 29382138
  28. [28]Lee D.Y. Jeong Y.T. Jeong S.C. Lee M.K. Min J.W. Lee J.W. Kim G.S. Lee S.E. Ahn Y.S. Kang H.C. Melanin biosynthesis inhibition effects of Ginsenoside Rb2 isolated from Panax ginseng Berry J Microbiol Biotechnol 25 2015 2011 2015 26437949
  29. [29]Liu Xy Xiao Y.K. Hwang E. Haeng J.J. Yi T.H. Antiphotoaging and antimelanogenesis properties of ginsenoside C-Y, a ginsenoside Rb2 metabolite from American ginseng PDD-ginsenoside Photochemistry and Photobiology 95 2019 1412 1423 31074886
  30. [30]Lee C.S. Nam G. Bae I.H. Park J. Whitening efficacy of ginsenoside F1 through inhibition of melanin transfer in cocultured human melanocytes-keratinocytes and three-dimensional human skin equivalent J Ginseng Res 43 2019 300 304 30962737 PMC6437421
  31. [31]Kim J.H. Baek E.J. Lee E.J. Yeom M.H. Park J.S. Lee K.W. Kang N.J. Ginsenoside F1 attenuates hyperpigmentation in B16F10 melanoma cells by inducing dendrite retraction and activating Rho signalling Exp Dermatol 24 2015 150 152 25381719
  32. [32]Wang D.-D. Jin Y. Wang C. Kim Y.-J. Perez Z.E.J. Baek N.I. Mathiyalagan R. Markus J. Yang D.-C. Rare ginsenoside Ia synthesized from F1 by cloning and overexpression of the UDP-glycosyltransferase gene from Bacillus subtilis: synthesis, characterization, and in vitro melanogenesis inhibition activity in BL6B16 cells Journal of Ginseng Research 42 2018 42 49 29348721 PMC5766694
  33. [33]Zhou Q.L. Yang X.W. Four new ginsenosides from red ginseng with inhibitory activity on melanogenesis in melanoma cells Bioorg Med Chem Lett 25 2015 3112 3116 26087936
  34. [34]Han J.S. Sung J.H. Lee S.K. Antimelanogenesis activity of hydrolyzed ginseng extract (GINST) via inhibition of JNK mitogen-activated protein kinase in B16F10 cells Journal of Food Science 81 2016 H2085 H2092 27356239
  35. [35]KimM D.S. Kim S.Y. Moon S.J. Chung J.H. Kim K.H. Cho K.H. Park K.C. Ceramide inhibits cell proliferation through Akt/PKB inactivation and decreases melanin synthesis in Mel-Ab cells Pigment Cell Research 14 2001 110 115 11310790
  36. [36]Kim Y.H. Kim D. Hong A.R. Kim J.H. Yoo H. Kim J. Kim I. Kang S.W. Chang S.E. Song Y. Therapeutic potential of rottlerin for skin hyperpigmentary disorders by inhibiting the transcriptional activity of CREB-regulated transcription coactivators The Journal of Investigative Dermatology 139 2019 2359 2367 31176710
  37. [37]Park P.J. Lee T.R. Cho E.-G. Substance P stimulates endothelin 1 secretion via endothelin-converting enzyme 1 and promotes melanogenesis in human melanocytes Journal of Investigative Dermatology 135 2015 551 559 25268585
  38. [38]Park C.W. Kim M.A. Choi Y. Kang I.C. Analysis of PKC beta-mediated tyrosinase phosphorylation using ProteoChip Biochip Journal 6 2012 391 395
  39. [39]Kim J. Kim Y.H. Bang S. Yoo H. Kim I. Chang S.E. Song Y.L. 765,314 Suppresses melanin synthesis by regulating tyrosinase activity Molecules 24 2019 PMC6412649 30795539
  40. [40]Roh E. Yun C.Y. Young Yun J. Park D. Doo Kim N. Yeon Hwang B. Jung S.H. Park S.K. Kim Y.B. Han S.B. cAMP-binding site of PKA as a molecular target of bisabolangelone against melanocyte-specific hyperpigmented disorder The Journal of Investigative Dermatology 133 2013 1072 1079 23254773
  41. [41]Horike N. Sakoda H. Kushiyama A. Ono H. Fujishiro M. Kamata H. Nishiyama K. Uchijima Y. Kurihara Y. Kurihara H. AMP-activated protein kinase activation increases phosphorylation of glycogen synthase kinase 3beta and thereby reduces cAMP-responsive element transcriptional activity and phosphoenolpyruvate carboxykinase C gene expression in the liver J Biol Chem 283 2008 33902 33910 18801732 PMC2662216
  42. [42]Lin M. Zhang B.-X. Zhang C. Shen N. Zhang Y.-Y. Wang A.-X. Tu C.-X. Ginsenosides Rb1 and Rg1 stimulate melanogenesis in human epidermal melanocytes via PKA/CREB/MITF signaling Evid Based Complement Alternat Med 2014 2014 PMC3988736 24799945
  43. [43]Kim E. Kim D. Yoo S. Hong Y.H. Han S.Y. Jeong S. Jeong D. Kim J.H. Cho J.Y. Park J. The skin protective effects of compound K, a metabolite of ginsenoside Rb1 from Panax ginseng J Ginseng Res 42 2018 218 224 29719469 PMC5925615
  44. [44]Wang L. Lu A.P. Yu Z.L. Wong R.N. Bian Z.X. Kwok H.H. Yue P.Y. Zhou L.M. Chen H. Xu M. The melanogenesis-inhibitory effect and the percutaneous formulation of ginsenoside Rb1 AAPS PharmSciTech 15 2014 1252 1262 24895076 PMC4179673
  45. [45]Xu X.F. Gao Y. Xu S.Y. Liu H. Xue X. Zhang Y. Zhang H. Liu M.N. Xiong H. Lin R.C. Remarkable impact of steam temperature on ginsenosides transformation from fresh ginseng to red ginseng J Ginseng Res 42 2018 277 287 29983609 PMC6026370
  46. [46]Im D.-S. Pro-resolving effect of ginsenosides as an anti-inflammatory mechanism of Panax ginseng Biomolecules 10 2020 444 PMC7175368 32183094
  47. [47]Yang Y. Yang W.S. Yu T. Sung G.H. Park K.W. Yoon K. Son Y.J. Hwang H. Kwak Y.S. Lee C.M. ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract J Ethnopharmacol 154 2014 218 228 24735861
  48. [48]Markey A.C. Black A.K. Rycroft R.J. Confetti-like depigmentation from hydroquinone Contact Dermatitis 20 1989 148 149 2706964
  49. [49]Kersey P. Stevenson C.J. Vitiligo and occupational exposure to hydroquinone from servicing self-photographing machines Contact Dermatitis 7 1981 285 287 7307500
  50. [50]Sasaki M. Kondo M. Sato K. Umeda M. Kawabata K. Takahashi Y. Suzuki T. Matsunaga K. Inoue SJPc research m Rhododendrol, a depigmentation-inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism 27 2014 754 763 24890809
  51. [51]Forster M. Bolzinger M.A. Fessi H. Briancon S. Topical delivery of cosmetics and drugs. Molecular aspects of percutaneous absorption and delivery European Journal of Dermatology: EJD 19 2009 309 323 19443302
  52. [52]Jeong Y.M. Oh W.K. Tran T.L. Kim W.K. Sung S.H. Bae K. Lee S. Sung J.H. Aglycone of Rh4 inhibits melanin synthesis in B16 melanoma cells: possible involvement of the protein kinase A pathway Biosci Biotechnol Biochem 77 2013 119 125 23291754

Cited by

Sorted by citations

Authors
Lee, H.-R., Jung, J. M., Seo, J.-Y., Chang, S. E., & Song, Y.
Affiliations
Asan Medical Center (KR)
Corresponding author
  • Chang, Sung Eun
  • Song, Youngsup
ORCID
Venue
Journal of Ginseng Research
Publisher
Elsevier BV
Published
2021-09
Volume
45
Issue
5
Pages
555-564
ISSN
1226-8453 (ISSN-L)
DOI
10.1016/j.jgr.2020.11.003
PMC
PMC8587488
OpenAlex
W3111100965
Cited by
28
References
0
Citations by year
2026: 5 · 2025: 9 · 2024: 6 · 2023: 2 · 2022: 5 · 2021: 1
FWCI
0.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Ginseng Research (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation of Korea (2020R1A2B5B02002286, 2020R1A4A4079708)
  • Korean Society of Ginseng
  • Asan Institute for Life Sciences, Asan Medical Center
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ginseng Biological Effects and Applications
  • Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
Keywords
ginsenoside Rf, Panax ginseng, anti-melanogenic activity, CREB, MITF, melanogenesis, tyrosinase, tyrosinase-related proteins, CRTC3, protein kinase A, melanocytes, ex vivo human skin

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review