Molecular & Cellular Toxicology

, Volume 15, Issue 1, pp 75–83 | Cite as

Ethanolic extract of Melia azedarach L. induces melanogenesis through the cAMP-PKA-CREB signaling pathway

  • Mi-Ok Kim
  • Se Jung Park
  • See-Hyoung Park
  • Sae Woong Oh
  • Seung Eun Lee
  • Ju Ah Yoo
  • Kitae Kwon
  • Jangsoon Kim
  • Min Hee Kim
  • Jae Youl ChoEmail author
  • Jongsung LeeEmail author
Original Paper



Since the cause of hypopigmentary skin disorders (hair graying and vitiligo) is typically unknown, there is no known cure for these disorders. Melia azedarach L. is used in Southeast Asia across China and Japan as a traditional medicine, and it has been reported to have various pharmacological properties. However, there have been no reports to demonstrate the involvement of M. azedarach L. in pigmentation. This study was conducted to investigate the effect of ethanolic extract of M. azedarach L. (MAE) on melanogenesis and to elucidate its mechanism of action in B16F10 mouse melanoma cells and human epidermal melanocytes.


Effects of MAE on melanogenesis and its mechanism of action were investigated using several assays, including melanin content, cellular tyrosinase activity, real-time PCR analysis, Western blot analysis, and ELISAs for cyclic AMP (cAMP), protein kinase A (PKA), cAMP response element binding (CREB) protein, and mitogen-activated protein kinases (MAPKs).


MAE increased the melanin content levels and cellular tyrosinase activity in B16F10 mouse melanoma cells and human epidermal melanocytes. In addition, the action mechanism of MAE-induced melanogenesis was examined in human epidermal melanocytes. It also upregulated the expressions of microphthalmia-associated transcription factor (MITF) gene and its downstream target genes, tyrosinase and tyrosinase-related protein (TRP) 1, but not TRP 2. MAE treatment increased the cAMP levels, PKA activity, and phosphorylation of CREB protein, its downstream signaling protein. However, MAE showed no effects on MAPKs (p42/44 MAPK, p38 MAPK, and c-Jun-N-terminal kinase (JNK)).


These findings indicate that MAE induces melanogenesis by upregulating the MITF gene through the cAMP-PKA-CREB signaling pathway, and they suggest its potential in the treatment of hypopigmentary skin diseases.


Ethanolic extract of Melia azedarach L. (MAE) Melanin cAMP PKA CREB 


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Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Nature B.V. 2019

Authors and Affiliations

  • Mi-Ok Kim
    • 1
  • Se Jung Park
    • 1
  • See-Hyoung Park
    • 2
  • Sae Woong Oh
    • 1
  • Seung Eun Lee
    • 1
  • Ju Ah Yoo
    • 1
  • Kitae Kwon
    • 1
  • Jangsoon Kim
    • 1
  • Min Hee Kim
    • 3
  • Jae Youl Cho
    • 4
    Email author
  • Jongsung Lee
    • 1
    Email author
  1. 1.Molecular Dermatology Laboratory and Biocosmetics Research Center, Department of Integrative Biotechnology, College of Biotechnology and BioengineeringSungkyunkwan UniversitySuwon, Gyeonggi-doRepublic of Korea
  2. 2.Department of Bio and Chemical EngineeringHongik UniversitySejongRepublic of Korea
  3. 3.Department of Physical Therapy, College of Health ScienceEulji UniversitySeongnam, Gyeonggi-doRepublic of Korea
  4. 4.Molecular Immunology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and BioengineeringSungkyunkwan UniversitySuwon, Gyeonggi-doRepublic of Korea

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