Influence of Four Phlomis Species on Melanogenesis in Human Malignant Melanoma (SKMEL-3) Cells

Document Type : Original paper


1 Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

2 Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.


Background and objectives: Phytochemical studies have shown that the Phlomis species are rich in polyphenolics and iridoid glycosides and many of them have shown potential value in different biological and pharmacological activities. In this study, we evaluated the effect of Phlomis persica, P. brugieri, P. olivieri and P. anisodontea extracts on melanin production in human malignant melanoma (SKMEL-3) cells. Methods: The anti-tyrosinase activity of the extracts was investigated using mushroom tyrosinase assay. Cytotoxicity potentials were examined through MTT assay on SKMEL-3 cell line and then the level of melanin formation in SKMEL-3 cells was determined. Results: The anti-tyrosinase activity of the Phlomis extracts was not remarkable (about 0.1 mg/mL). All extracts significantly increased the melanin content in SKMEL-3 cells at 0.25 mg/mL and among them P. anisodontea extract seemed to be more efficient in stimulating melanin production. Conclusion: Based on our results, we suggest these total extracts particularly P. anisodontea extract contain the potent skin browning agents that can be used in pharmaceutical and cosmetic products.


[1] Langfelder K, Streibel M, Jahn B, Haase G, Brakhage AA. Biosynthesis of fungal melanins and their importance for human pathogenic fungi. Fungal Genet Biol. 2003; 38(2): 143-158.
[2] Casadevall A, Rosas AL, Nosanchuk JD. Melanin and virulence in Cryptococcus neoformans. Curr Opin Microbiol.2000; 3(4): 354-358.
[3] El-Obeid A, Al-Harbi S, Al-Jomah N, Hassib A. Herbal melanin modulates tumor necrosis factor alpha (TNF- α), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) production. Phytomed.2006; 13(5): 324-333.
[4] Sava VM, Galkin BN, Hong MY, Yang PC, Huang GS. A novel melanin-like pigment derived from black tea leaves with immuno-stimulating activity. Food Res Int. 2001; 34(4): 337-343.
[5] Solano F, Briganti S, Picardo M, Ghanem GH. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res. 2006; 19(6): 550-571.
[6] Yao C, Jin CL, Oh JH, Oh IG, Park CH, Chung JH. Ardisia crenata extract stimulates melanogenesis in B16F10 melanoma cells through inhibiting ERK1/2 and Akt activation. Mol Med Rep. 2015; 11(1): 653-657.
[7] Nordlund JJ, Boissy RE, Hearing VJ, Oetting WS, King RA, Ortonne JP. The pigmentary system: physiology and pathophysiology, 2nd ed. Edinburgh: Blackwell Science, 2006.
[8] Chang TS. An updated review of tyrosinase inhibitors. Int J Mol Sci. 2009; 10(6): 2440-2475.
[9] Niu C, Aisa HA. Upregulation of melanogenesis and tyrosinase activity: potential agents for vitiligo. Molecules. 2017; 22(8): 1-28.
[10] Limem-Ben Amor I, Boubaker J, Ben Sgaier M, Skandrani I, Bhouri W, Neffati A, Kilani S, Bouhlel I, Ghedira K, Chekir-Ghedira L. Phytochemistry and biological activities of Phlomis species. J Ethnopharmacol. 2009; 125(2): 183-202.
[11] Aghakhani F, Kharazian N, Lori Gooini Z. Flavonoid constituents of Phlomis (Lamiaceae) species using liquid chromatography mass spectrometry. Phytochem Anal. 2018; 29(2): 180-195.
[12] Liu-Smith F, Meyskens FL. Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma. Mol Nutr Food Res. 2016; 60(6): 1264-1274.
[13] Takekoshi S, Nagata H, Kitatani K. Flavonoids enhance melanogenesis in human melanoma cells. Tokai J Exp Clin Med.2014; 39(3): 116-121.
[14] Huang YC, Yang CH, Chiou YL. Citrus flavanone naringenin enhances melanogenesis through the activation of Wnt/β-catenin signalling in mouse melanoma cells. Phytomed. 2011; 18(14): 1244-1249.
[15] Son YO, Lee SA, Kim SS, Jang YS, Chun JC, Lee JC. Acteoside inhibits melanogenesis in B16F10 cells through ERK activation and tyrosinase down-regulation. J Pharm Pharmacol. 2011; 63(10): 1309-1319.
[16] Salimi M, Sarkhail P, Tahmasvand R, Baeeri M. Determination of anti-melanogenic activity of Phlomis kurdica in human melanoma SKMEL-3 cells. Iran J Pharm Res. 2016; 12(1): 1-10.
[17] Sarkhail P, Salimi M, Sarkheil P, Heidarnezhad F, Saeidnia S. Evaluation of anti-melanogenic and cytotoxic activities of Phlomis caucasica on human melanoma SKMEL-3 cells. Int J Cancer Manag. 2017; 10(3): 1-7.
[18] Salimi M, Sarkhail P, Sarkheil P, Mostafapour Kandelous H, Baeeri M. Evaluation of anti-melanogenic activity of Ziziphus jujuba fruits obtained by two different extraction methods. Res J Pharmacogn. 2016; 3(2): 1-7.
[19] Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2): 55-63.
[20] Chan YY, Kim KH, Cheah SH. Inhibitory effects of Sargassum polycystum on tyrosinase activity and melanin formation in B16F10 murine melanoma cells. J Ethnopharmacol. 2011; 137(3): 1183-1188.
[21] Sarkhail P, Sahranavard S, Nikan M, Gafari S, Eslami-Tehrani B. Evaluation of the cytotoxic activity of extracts from six species of Phlomis genus. J App Pharm Sci. 2017; 7(2): 180-184.