Cited by 6melanin and skin pigmentationSkin Protection and AgingMelanoma and MAPK Pathways

Giant Centella asiatica , a novel cultivar rich in madecassoside and asiaticoside, suppresses α‑melanocyte‑stimulating hormone‑induced melanogenesis through MC1R binding

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Seo, Jiwon, Jeong, Chanhyeok, Oh, Seung, Lee, Sung-Young, Park, Han, Seo, Dae, Yoo, Dae, Sim, Woo-Jin +4 more·2024·International Journal of Molecular Medicine

Abstract

(CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.

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Authors
Seo, J., Jeong, C., Oh, S., Lee, S.-Y., Park, H., Seo, D., Yoo, D., Sim, W.-J., Lim, T.-G., Park, J. H. Y., Lee, C., & Lee, K.
Affiliations
  • Seoul National University (KR)
  • ASK Company Co., Ltd., Daegu 42176, Republic of Korea
  • Sejong University (KR)
Corresponding author
  • Lee, Chang
  • Lee, Ki
Venue
International Journal of Molecular Medicine
Published
2024-11-04
Volume
55
Issue
1
ISSN
  • 1107-3756 (ISSN-L)
  • 1791-244X
OpenAlex
W4404045325
Cited by
6
References
43
Citations by year
2026: 4 · 2025: 2
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • International Journal of Molecular Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation (2020M3H1A1073304)
  • Seoul National University
  • Ministry of Science and ICT, South Korea (2020M3H1A1073304)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
Centella asiatica, madecassoside, asiaticoside, anti-melanogenic activity, melanogenesis, MITF, CREB, PKA signaling, B16F10 melanoma cells, skin lightening, skin pigmentation disorders
MeSH terms
Melanogenesis, alpha-MSH, Animals, Humans, Melanins, Melanoma, Experimental, Plant Extracts, Skin Pigmentation, Triterpenes, Centella, Receptor, Melanocortin, Type 1, Cell Line, Tumor, Mice, Molecular Docking Simulation

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