Ethanolic extract of Melia azedarach L. induces melanogenesis through the cAMP-PKA-CREB signaling pathway
- 18 Downloads
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.
KeywordsEthanolic extract of Melia azedarach L. (MAE) Melanin cAMP PKA CREB
Unable to display preview. Download preview PDF.
- 6.McDonough, P. H. & Schwartz, R. A. Premature hair graying. Cutis 89, 161–165 (2012).Google Scholar
- 11.Lin, M. et al. Ginsenosides Rb1 and Rg1 stimulate melanogenesis in human epidermal melanocytes via PKA/CREB/MITF signaling. Evid Based Complement Alternat Med 2014, 892073 (2014).Google Scholar
- 13.Namba, T. in The Encyclopedia of Wakan-Yaku (Traditional Sino-Japanese Medicines) with Color Pictures Vol. I. Revised edition (Hoikusya Co. Ltd., Osaka, 1994).Google Scholar
- 14.Okada, M. in Newly Revised Illustrated Medicinal Plants of World (Hokuryukan Publishing Co. Ltd., Tokyo, 2002).Google Scholar
- 15.Vishnukanta, A. C. Rana. Melia azedarach: A phytopharmacological review. Pharmacogn Rev 2, 173–179 (2008).Google Scholar
- 16.Khan, M. F. et al. Bioactivity-guided chemical analysis of Melia azedarach L. (Meliaceae), displaying antidiabetic activity. Fitoterapia 98, 98–103 (2014).Google Scholar
- 20.Fu, Y. T., Lee, C. W., Ko, H. H. & Yen, F. L. Extracts of Artocarpus communis decrease α-melanocyte stimulating hormone-induced melanogenesis through activation of ERK and JNK signaling Pathways. Scientific WorldJournal 2014, 724314 (2014).Google Scholar
- 22.Huang, H. C., Chang, S. J., Wu, C. Y., Ke, H. J. & Chang, T. M. -Shogaol inhibits α-MSH-induced melanogenesis through the acceleration of ERK and PI3K/Akt-mediated MITF degradation. Biomed Res Int 2014, 842569 (2014).Google Scholar