Ethyl Acetate Fraction from a . Don Extract Inhibits ɑ-MSH-Induced Melanogenesis Through the CAMP/CREB Pathway

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jan 11

PMID 38203322

Authors

Yon-Suk Kim

Eun-Bin Lee

Ye-Ji Yu

Ga-Won Kim

Woo-Jung Kim

Dong-Kug Choi

Affiliations

Soon will be listed here.

Abstract

The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether extract and its fractions have potential as natural skin-lightening agents. Initially, we screened various fractions of extract using an in vitro antioxidant assay. Then, the inhibitory effects of extract and its fraction on melanogenesis and the related mechanisms were investigated in B16F1 melanoma cells. The results showed that the ethyl acetate fraction (EF) from extract markedly inhibited melanin synthesis in a dose-dependent manner at non-toxic concentrations. Furthermore, EF downregulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine into melanin. We also found that EF decreased the microphthalmia-associated transcription factor (MITF) at the protein and mRNA levels. EF increased the phosphorylation of ERK and suppressed the phosphorylation of JNK and p38 in ɑ-MSH-induced B16F1 cells. These results indicate that EF can regulate the MAPK pathway. In addition, EF has an anti-melanogenic effect via the downregulation of intracellular cyclic-AMP (cAMP). Nineteen major compounds of EF were identified using LC-MS/MS. Taken together, these results suggest that EF may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and in topical treatments for hyperpigmentation disorders.

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References

Moon M, Choi B, Oh G, Pae H, Kim J, Oh H . Catalposide protects Neuro 2A cells from hydrogen peroxide-induced cytotoxicity via the expression of heme oxygenase-1. Toxicol Lett. 2003; 145(1):46-54. DOI: 10.1016/s0378-4274(03)00268-6. View

Sato K, Ando R, Kobayashi H, Nishio T . 2-Ethoxybenzamide stimulates melanin synthesis in B16F1 melanoma cells via the CREB signaling pathway. Mol Cell Biochem. 2016; 423(1-2):39-52. DOI: 10.1007/s11010-016-2823-x. View

Saeedi M, Eslamifar M, Khezri K . Kojic acid applications in cosmetic and pharmaceutical preparations. Biomed Pharmacother. 2018; 110:582-593. DOI: 10.1016/j.biopha.2018.12.006. View

Wu L, Lin Y, Yang S, Weng Y, Tsai Y . Antimelanogenic effect of c-phycocyanin through modulation of tyrosinase expression by upregulation of ERK and downregulation of p38 MAPK signaling pathways. J Biomed Sci. 2011; 18:74. PMC: 3210093. DOI: 10.1186/1423-0127-18-74. View

Pearson G, Robinson F, Beers Gibson T, Xu B, Karandikar M, Berman K . Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001; 22(2):153-83. DOI: 10.1210/edrv.22.2.0428. View

Draelos Z . Skin lightening preparations and the hydroquinone controversy. Dermatol Ther. 2007; 20(5):308-13. DOI: 10.1111/j.1529-8019.2007.00144.x. View

Xu H, Hu G, Dong J, Wei Q, Shao H, Lei M . Antioxidative activities and active compounds of extracts from Catalpa plant leaves. ScientificWorldJournal. 2014; 2014:857982. PMC: 4238400. DOI: 10.1155/2014/857982. View

Huang H, Hsieh W, Niu Y, Chang T . Inhibition of melanogenesis and antioxidant properties of Magnolia grandiflora L. flower extract. BMC Complement Altern Med. 2012; 12:72. PMC: 3404006. DOI: 10.1186/1472-6882-12-72. View

Kim S, Kim M, Choi Y, Kim B, Kim K, Park K . Down-regulation of tyrosinase, TRP-1, TRP-2 and MITF expressions by citrus press-cakes in murine B16 F10 melanoma. Asian Pac J Trop Biomed. 2013; 3(8):617-22. PMC: 3703554. DOI: 10.1016/S2221-1691(13)60125-2. View

10.

Pae H, Oh G, Choi B, Shin S, CHAI K, Oh H . Inhibitory effects of the stem bark of Catalpa ovata G. Don. (Bignoniaceae) on the productions of tumor necrosis factor-alpha and nitric oxide by the lipopolisaccharide-stimulated RAW 264.7 macrophages. J Ethnopharmacol. 2003; 88(2-3):287-91. DOI: 10.1016/s0378-8741(03)00228-9. View

11.

Ando H, Kondoh H, Ichihashi M, Hearing V . Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J Invest Dermatol. 2007; 127(4):751-61. DOI: 10.1038/sj.jid.5700683. View

12.

Yu J, Kim A . Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells. J Biomed Sci. 2010; 17 Suppl 1:S45. PMC: 2994384. DOI: 10.1186/1423-0127-17-S1-S45. View

13.

Brenner M, Hearing V . The protective role of melanin against UV damage in human skin. Photochem Photobiol. 2008; 84(3):539-49. PMC: 2671032. DOI: 10.1111/j.1751-1097.2007.00226.x. View

14.

Cho J, Kim H, Choi G, Jang K, Lim H, Lim C . Dehydro-alpha-lapachone isolated from Catalpa ovata stems: activity against plant pathogenic fungi. Pest Manag Sci. 2006; 62(5):414-8. DOI: 10.1002/ps.1180. View

15.

Han J, Sung J, Lee S . Antimelanogenesis Activity of Hydrolyzed Ginseng Extract (GINST) via Inhibition of JNK Mitogen-activated Protein Kinase in B16F10 Cells. J Food Sci. 2016; 81(8):H2085-92. DOI: 10.1111/1750-3841.13380. View

16.

Park S, Shin H, Park Y, Choi I, Park B, Lee K . Characterization of inhibitory constituents of NO production from Catalpa ovata using LC-MS coupled with a cell-based assay. Bioorg Chem. 2018; 80:57-63. DOI: 10.1016/j.bioorg.2018.05.023. View

17.

Huang H, Han X, Hwang B, Park J, Yoo S, Lee H . Effects of catalpalactone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells. Environ Toxicol Pharmacol. 2011; 26(1):86-91. DOI: 10.1016/j.etap.2008.02.005. View

18.

Ortonne J . Photoprotective properties of skin melanin. Br J Dermatol. 2002; 146 Suppl 61:7-10. DOI: 10.1046/j.1365-2133.146.s61.3.x. View

19.

Gilchrest B, Eller M, Geller A, Yaar M . The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med. 1999; 340(17):1341-8. DOI: 10.1056/NEJM199904293401707. View

20.

Chung Y, Hyun C . Inhibitory Effects of Pinostilbene Hydrate on Melanogenesis in B16F10 Melanoma Cells via ERK and p38 Signaling Pathways. Int J Mol Sci. 2020; 21(13). PMC: 7369948. DOI: 10.3390/ijms21134732. View