Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Traditional Medicine
  4. Fast Track Articles
  5. Fast Track Article
image of Exploring the Anti-melanogenic, Antioxidant, and Anti-inflammatory Activities of A Composition: Glabridin, Resveratrol and Ellagic Acid

Abstract

Background

Plant extracts have wide applications in food, nutrition, and cosmetics, which results in a deeper investigation of natural ingredients. Numerous natural ingredients have been demonstrated to exhibit multiple activities, including antioxidation, anti-inflammation, and anti-melanogenesis. However, their combinations have not been well investigated, which could provide stronger performance with less toxicity and easier applications.

Methods

We used B16F10 cells treated with alpha-melanocyte stimulating hormone (αMSH) for melanogenesis-related studies, including cellular melanin content, tyrosinase activity, and gene or protein expression. MTT assay was used to evaluate cell viability. DPPH scavenging activity was measured for antioxidation. Nitric oxide (NO) content was evaluated in lipopolysaccharide (LPS) treated RAW264.7 cells to indicate the performance on anti-inflammation.

Results

In this study, six different compounds and their combinations were tested for melanogenesis. The results showed that the combination of glabridin, resveratrol, and ellagic acid (GRE) exhibited the highest efficiency, which was mainly manifested as inhibition of melanin production and tyrosinase activity, higher DPPH scavenging rate, and inhibition of nitric oxide (NO) production. Meanwhile, our results showed that GRE could significantly downregulate the expression of microphthalmia-associated transcription factor (MITF) related genes and proteins and could also inhibit the phosphorylation of cyclic AMP response element-binding protein (CREB), which was the upstream signal of MITF.

Conclusion

The results suggest GRE exhibits high efficiency in inhibiting anti-melanogenesis, antioxidation, and anti-inflammation. Furthermore, GRE could downregulate the phosphorylation of the CREB and MITF signal pathway, which provides a theoretical basis for its application in pigmentation disorder disease and cosmetics.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ctm/10.2174/0122150838296794240610130259
2024-11-29
2025-01-22

  • From This Site

    /content/journals/ctm/10.2174/0122150838296794240610130259
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Ohbayashi N. Fukuda M. Recent advances in understanding the molecular basis of melanogenesis in melanocytes. F1000 Res. 2020 9 608 10.12688/f1000research.24625.1 32595944
    [Google Scholar]
  2. Chan I.L. Cohen S. da Cunha M.G. Maluf L.C. Characteristics and management of Asian skin. Int. J. Dermatol. 2019 58 2 131 143 10.1111/ijd.14153 30039861
    [Google Scholar]
  3. Cichorek M. Wachulska M. Stasiewicz A. Tymińska A. Skin melanocytes: Biology and development. Postepy Dermatol. Alergol. 2013 1 1 30 41 10.5114/pdia.2013.33376 24278043
    [Google Scholar]
  4. Moreiras H. Seabra M.C. Barral D.C. Melanin transfer in the epidermis: The pursuit of skin pigmentation control mechanisms. Int. J. Mol. Sci. 2021 22 9 4466 10.3390/ijms22094466 33923362
    [Google Scholar]
  5. Solano F. Photoprotection and skin pigmentation: Melanin-related molecules and some other new agents obtained from natural sources. Molecules 2020 25 7 1537 10.3390/molecules25071537 32230973
    [Google Scholar]
  6. Rachmin I. Ostrowski S.M. Weng Q.Y. Fisher D.E. Topical treatment strategies to manipulate human skin pigmentation. Adv. Drug Deliv. Rev. 2020 153 65 71 10.1016/j.addr.2020.02.002 32092380
    [Google Scholar]
  7. Thawabteh A.M. Jibreen A. Karaman D. Thawabteh A. Karaman R. Skin pigmentation types, causes and treatment : A review. Molecules 2023 28 12 4839 10.3390/molecules28124839 37375394
    [Google Scholar]
  8. Li Y. Huang J. Lu J. Ding Y. Jiang L. Hu S. Chen J. Zeng Q. The role and mechanism of Asian medicinal plants in treating skin pigmentary disorders. J. Ethnopharmacol. 2019 245 112173 10.1016/j.jep.2019.112173 31445129
    [Google Scholar]
  9. Qian W. Liu W. Zhu D. Cao Y. Tang A. Gong G. Su H. Natural skin‑whitening compounds for the treatment of melanogenesis (Review). Exp. Ther. Med. 2020 20 1 173 185 10.3892/etm.2020.8687 32509007
    [Google Scholar]
  10. Zhao W. Yang A. Wang J. Huang D. Deng Y. Zhang X. Qu Q. Ma W. Xiong R. Zhu M. Huang C. Potential application of natural bioactive compounds as skin‐whitening agents: A review. J. Cosmet. Dermatol. 2022 21 12 6669 6687 10.1111/jocd.15437 36204978
    [Google Scholar]
  11. Burki T. Skin-whitening creams: worth the risk? Lancet Diabetes Endocrinol. 2021 9 1 10 10.1016/S2213‑8587(20)30400‑9 33248480
    [Google Scholar]
  12. Nordin F.N.M. Aziz A. Zakaria Z. Wan Mohamed Radzi C.W.J. A systematic review on the skin whitening products and their ingredients for safety, health risk, and the halal status. J. Cosmet. Dermatol. 2021 20 4 1050 1060 10.1111/jocd.13691 32854162
    [Google Scholar]
  13. Zheng Y. Du X. Zhang L. Jia T. Zhang H. Peng B. Hao Y. Tong Z. Che D. Geng S. Hydroquinone‐induced skin irritant reaction could be achieved by activating mast cells via mas‐related G protein–coupled receptor X2. Exp. Dermatol. 2023 32 4 436 446 10.1111/exd.14723 36463492
    [Google Scholar]
  14. Matsumoto M. Todo H. Akiyama T. Hirata-Koizumi M. Sugibayashi K. Ikarashi Y. Ono A. Hirose A. Yokoyama K. Risk assessment of skin lightening cosmetics containing hydroquinone. Regul. Toxicol. Pharmacol. 2016 81 128 135 10.1016/j.yrtph.2016.08.005 27521610
    [Google Scholar]
  15. Yoshikawa M. Sumikawa Y. Hida T. Kamiya T. Kase K. Ishii-Osai Y. Kato J. Kan Y. Kamiya S. Sato Y. Yamashita T. Clinical and epidemiological analysis in 149 cases of rhododendrol‐induced leukoderma. J. Dermatol. 2017 44 5 582 587 10.1111/1346‑8138.13694 27882588
    [Google Scholar]
  16. Westerhof W. Kooyers T.J. Hydroquinone and its analogues in dermatology a potential health risk. J. Cosmet. Dermatol. 2005 4 2 55 59 10.1111/j.1473‑2165.2005.40202.x 17166200
    [Google Scholar]
  17. Zaid A.N. Al Ramahi R. Depigmentation and anti-aging treatment by natural molecules. Curr. Pharm. Des. 2019 25 20 2292 2312 10.2174/1381612825666190703153730 31269882
    [Google Scholar]
  18. Dej-adisai S. Koyphokaisawan N. Wattanapiromsakul C. Nuankaew W. Kang T.H. Pitakbut T. In Vitro, In Vivo, and In Silico analyses of molecular anti-pigmentation mechanisms of selected thai rejuvenating remedy and bioactive metabolites. Molecules 2023 28 3 958 10.3390/molecules28030958 36770624
    [Google Scholar]
  19. Campelo J.E.S. Nascimento M.O. Carvalho A.L.M. Santos H.S.P. Almeida J.O.C.S. Alves M.M.M. Arcanjo D.D.R. Tavares Neto J.M. Muratori M.C.S. Costa A.P.R. Evaluation of the acute toxicity of ellagic acid and gallic acid incorporated in Poloxamer407® gel, in Zophobas morio larvae. Toxicol. In Vitro 2024 95 105727 10.1016/j.tiv.2023.105727 37993026
    [Google Scholar]
  20. Yang H.L. Lin C.P. Vudhya Gowrisankar Y. Huang P.J. Chang W.L. Shrestha S. Hseu Y.C. The anti-melanogenic effects of ellagic acid through induction of autophagy in melanocytes and suppression of UVA-activated α-MSH pathways via Nrf2 activation in keratinocytes. Biochem. Pharmacol. 2021 185 114454 10.1016/j.bcp.2021.114454 33545118
    [Google Scholar]
  21. Na J.I. Shin J.W. Choi H.R. Kwon S.H. Park K.C. Resveratrol as a multifunctional topical hypopigmenting agent. Int. J. Mol. Sci. 2019 20 4 956 10.3390/ijms20040956 30813264
    [Google Scholar]
  22. Chen J. Li Q. Ye Y. Huang Z. Ruan Z. Jin N. Phloretin as both a substrate and inhibitor of tyrosinase: Inhibitory activity and mechanism. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2020 226 117642 10.1016/j.saa.2019.117642 31614273
    [Google Scholar]
  23. Huang H.C. Chiu S.H. Chang T.M. Inhibitory effect of [6]-gingerol on melanogenesis in B16F10 melanoma cells and a possible mechanism of action. Biosci. Biotechnol. Biochem. 2011 75 6 1067 1072 10.1271/bbb.100851 21670536
    [Google Scholar]
  24. Desmedt B. Courselle P. De Beer J.O. Rogiers V. Grosber M. Deconinck E. De Paepe K. Overview of skin whitening agents with an insight into the illegal cosmetic market in Europe. J. Eur. Acad. Dermatol. Venereol. 2016 30 6 943 950 10.1111/jdv.13595 26953335
    [Google Scholar]
  25. Saeedi M. Khezri K. Seyed Zakaryaei A. Mohammadamini H. A comprehensive review of the therapeutic potential of α‐arbutin. Phytother. Res. 2021 35 8 4136 4154 10.1002/ptr.7076 33724594
    [Google Scholar]
  26. Saeedi M. Eslamifar M. Khezri K. Kojic acid applications in cosmetic and pharmaceutical preparations. Biomed. Pharmacother. 2019 110 582 593 10.1016/j.biopha.2018.12.006 30537675
    [Google Scholar]
  27. Prabhu D. Ravikumar P. Novel user‐friendly night care spray to manage skin darkening. J. Cosmet. Dermatol. 2020 19 6 1439 1446 10.1111/jocd.13187 31628727
    [Google Scholar]
  28. Pillaiyar T. Manickam M. Namasivayam V. Skin whitening agents: Medicinal chemistry perspective of tyrosinase inhibitors. J. Enzyme Inhib. Med. Chem. 2017 32 1 403 425 10.1080/14756366.2016.1256882 28097901
    [Google Scholar]
  29. Gelmi M.C. Houtzagers L.E. Strub T. Krossa I. Jager M.J. MITF in normal melanocytes, cutaneous and uveal melanoma: A delicate balance. Int. J. Mol. Sci. 2022 23 11 6001 10.3390/ijms23116001 35682684
    [Google Scholar]
  30. Levy C. Khaled M. Fisher D.E. MITF: Master regulator of melanocyte development and melanoma oncogene. Trends Mol. Med. 2006 12 9 406 414 10.1016/j.molmed.2006.07.008 16899407
    [Google Scholar]
  31. Abrahamian C. Grimm C. Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma. Biomolecules 2021 11 7 1021 10.3390/biom11071021 34356645
    [Google Scholar]
  32. Serre C. Busuttil V. Botto J.M. Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation. Int. J. Cosmet. Sci. 2018 40 4 328 347 10.1111/ics.12466 29752874
    [Google Scholar]
  33. Hertzman Johansson C. Azimi A. Frostvik Stolt M. Shojaee S. Wiberg H. Grafström E. Hansson J. Egyházi Brage S. Association of MITF and other melanosome-related proteins with chemoresistance in melanoma tumors and cell lines. Melanoma Res. 2013 23 5 360 365 10.1097/CMR.0b013e328362f9cd 23921446
    [Google Scholar]
  34. Nguyen N.T. Fisher D.E. MITF and UV responses in skin: From pigmentation to addiction. Pigment Cell Melanoma Res. 2019 32 2 224 236 10.1111/pcmr.12726 30019545
    [Google Scholar]
  35. Yamaguchi Y. Hearing V.J. Physiological factors that regulate skin pigmentation. Biofactors 2009 35 2 193 199 10.1002/biof.29 19449448
    [Google Scholar]
  36. Yardman-Frank J.M. Fisher D.E. Skin pigmentation and its control: From ultraviolet radiation to stem cells. Exp. Dermatol. 2021 30 4 560 571 10.1111/exd.14260 33320376
    [Google Scholar]
  37. Pan C. Liu X. Zheng Y. Zhang Z. Li Y. Che B. Liu G. Zhang L. Dong C. Aisa H.A. Du Z. Yuan Z. The mechanisms of melanogenesis inhibition by glabridin: Molecular docking, PKA/MITF and MAPK/MITF pathways. Food Sci. Hum. Wellness 2023 12 1 212 222 10.1016/j.fshw.2022.07.011
    [Google Scholar]
  38. Rzepka Z. Buszman E. Beberok A. Wrześniok D. From tyrosine to melanin: Signaling pathways and factors regulating melanogenesis. Postepy Hig. Med. Dosw. 2016 70 0 695 708 10.5604/17322693.1208033 27356601
    [Google Scholar]
  39. Markiewicz E. Karaman-Jurukovska N. Mammone T. Idowu O.C. Post-inflammatory hyperpigmentation in dark skin: Molecular mechanism and skincare implications. Clin. Cosmet. Investig. Dermatol. 2022 15 2555 2565 10.2147/CCID.S385162 36466945
    [Google Scholar]
  40. Kaufman B.P. Aman T. Alexis A.F. Postinflammatory hyperpigmentation: Epidemiology, clinical presentation, pathogenesis and treatment. Am. J. Clin. Dermatol. 2018 19 4 489 503 10.1007/s40257‑017‑0333‑6 29222629
    [Google Scholar]
  41. Yamaoka Y. Ohguchi K. Itoh T. Nozawa Y. Akao Y. Effects of theaflavins on melanin biosynthesis in mouse b16 melanoma cells. Biosci. Biotechnol. Biochem. 2009 73 6 1429 1431 10.1271/bbb.80880 19502752
    [Google Scholar]
  42. Gu Y. Han J. Jiang C. Zhang Y. Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res. Rev. 2020 59 101036 10.1016/j.arr.2020.101036 32105850
    [Google Scholar]
  43. Mohania D. Chandel S. Kumar P. Verma V. Digvijay K. Tripathi D. Choudhury K. Mitten S.K. Shah D. Ultraviolet radiations: Skin defense-damage mechanism. Adv. Exp. Med. Biol. 2017 996 71 87 10.1007/978‑3‑319‑56017‑5_7 29124692
    [Google Scholar]
  44. Letelier M.E. Molina-Berríos A. Cortés-Troncoso J. Jara-Sandoval J. Holst M. Palma K. Montoya M. Miranda D. González-Lira V. DPPH and oxygen free radicals as pro-oxidant of biomolecules. Toxicol. In Vitro 2008 22 2 279 286 10.1016/j.tiv.2007.08.002 17888621
    [Google Scholar]
  45. Shenoy A. Madan R. Post-inflammatory hyperpigmentation: A review of treatment strategies. J. Drugs Dermatol. 2020 19 8 763 768 10.36849/JDD.2020.4887 32845587
    [Google Scholar]
  46. Vachtenheim J. Borovanský J. “Transcription physiology” of pigment formation in melanocytes: Central role of MITF. Exp. Dermatol. 2010 19 7 617 627 10.1111/j.1600‑0625.2009.01053.x 20201954
    [Google Scholar]
  47. Loftus S.K. Antonellis A. Matera I. Renaud G. Baxter L.L. Reid D. Wolfsberg T.G. Chen Y. Wang C. Prasad M.K. Bessling S.L. McCallion A.S. Green E.D. Bennett D.C. Pavan W.J. Gpnmb is a melanoblast‐expressed, MITF‐dependent gene. Pigment Cell Melanoma Res. 2009 22 1 99 110 10.1111/j.1755‑148X.2008.00518.x 18983539
    [Google Scholar]
  48. Hu S. Bai S. Dai Y. Yang N. Li J. Zhang X. Wang F. Zhao B. Bao G. Chen Y. Wu X. Deubiquitination of MITF-M regulates melanocytes proliferation and apoptosis. Front. Mol. Biosci. 2021 8 692724 10.3389/fmolb.2021.692724 34179099
    [Google Scholar]
  49. Goding C.R. Arnheiter H. MITF—the first 25 years. Genes Dev. 2019 33 15-16 983 1007 10.1101/gad.324657.119 31123060
    [Google Scholar]
  50. He J. Chen W. Chen X. Xie Y. Zhao Y. Tian T. Guo B. Cai X. Tetrahedral framework nucleic acid loaded with glabridin: A transdermal delivery system applicated to anti‐hyperpigmentation. Cell Prolif. 2023 56 12 e13495 10.1111/cpr.13495 37132449
    [Google Scholar]
  51. Zhou D.D. Luo M. Huang S.Y. Saimaiti A. Shang A. Gan R.Y. Li H.B. Effects and mechanisms of resveratrol on aging and age-related diseases. Oxid. Med. Cell. Longev. 2021 2021 1 15 10.1155/2021/9932218 34336123
    [Google Scholar]
  52. Zhu H. Yan Y. Jiang Y. Meng X. Ellagic acid and its anti-aging effects on central nervous system. Int. J. Mol. Sci. 2022 23 18 10937 10.3390/ijms231810937 36142849
    [Google Scholar]
  53. Kim E.S. Chang H. Choi H. Shin J.H. Park S.J. Jo Y.K. Choi E.S. Baek S.Y. Kim B.G. Chang J.W. Kim J.C. Cho D.H. Autophagy induced by resveratrol suppresses α ‐ MSH ‐induced melanogenesis. Exp. Dermatol. 2014 23 3 204 206 10.1111/exd.12337 24499351
    [Google Scholar]
  54. Nyamba I. Lechanteur A. Semdé R. Evrard B. Physical formulation approaches for improving aqueous solubility and bioavailability of ellagic acid: A review. Eur. J. Pharm. Biopharm. 2021 159 198 210 10.1016/j.ejpb.2020.11.004 33197529
    [Google Scholar]
/content/journals/ctm/10.2174/0122150838296794240610130259
Loading
Exploring the Anti-melanogenic, Antioxidant, and Anti-inflammatory Activities of A Composition: Glabridin, Resveratrol and Ellagic Acid
Bentham Science Publishers ; https://doi.org/10.2174/0122150838296794240610130259
/content/journals/ctm/10.2174/0122150838296794240610130259
/content/journals/ctm/10.2174/0122150838296794240610130259
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: MITF ; glabridin ; tyrosinase ; ellagic acid ; Melanogenesis ; resveratrol

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test