Modified Riceberry rice extract suppresses melanogenesis-associated cell differentiation through tyrosinase-mediated MITF downregulation on B16 cells and in vivo zebrafish embryos

Teerapat Rodboon , Sasithorn Sirilun, Seiji Okada, Ryusho Kariya, Thapana Chontananarth, Prasit Suwannalert

Abstract


Background and purpose: Excessive melanin production caused by overactive tyrosinase (TYR) enzyme results in several dermatological problems. The TYR inhibitor, derived from metabolite changes during fermentation, has been well recognized for pigmentation control.

Experimental approach: This study is interested in alternative anti-melanogenic agents from bio-modified Riceberry rice through fermentation. Modified Riceberry rice extract (MRB) was evaluated for its cytotoxicity, melanin content, melanin excretion, and TYR activity in B16 cells. TYR and their melanogenesis-related molecules such as TYR-related proteins-1 and -2, and microphthalmia-associated transcription factor (MITF) were determined. The anti-melanogenic activity and toxicity were also tested using the embryonic zebrafish model. Furthermore, comprehensive genotoxicity testing was verified by cytokinesis-block micronucleus cytome assay.

Findings/Results: The study found that non-cytotoxic concentrations of MRB at 20 and 40 mg/mL inhibited melanogenesis and melanin excretion by interfering B16 cell morphology. Cellular TYR enzymatic activity was also suppressed in the treated cells. The mRNA transcription and protein expression levels of TYR and MITF decreased by dose-dependent and time-dependent manners with MRB treatment. In the animal model, MRB was found to be safe and potent for melanogenesis-related TYR inhibition in embryonic zebrafish at 20 and 30 mg/mL. The toxicity of effective doses of MRB showed no genotoxicity and mutagenicity.

Conclusion and implications: This study suggests that MRB has anti-melanogenesis potential through TYR and its-related protein inhibitions. MRB is also safe for applications and maybe a promising anti-melanogenic agent for hyperpigmentation control.

Keywords


Fermentation; Melanogenesis; MITF; Riceberry rice; Tyrosinase.

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References


Park HY, Kosmadaki M, Yaar M, Gilchrest BA. Cellular mechanisms regulating human melanogenesis. Cell Mol Life Sci. 2009;66(9):1493-1506.

DOI: 10.1007/s00018-009-8703-8.

Busca R, Ballotti R. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res. 2000;13(2):60-69.

DOI: 10.1034/j.1600-0749.2000.130203.x.

Villareal MO, Han J, Ikuta K, Isoda H. Mechanism of Mitf inhibition and morphological differentiation effects of hirsein A on B16 melanoma cells revealed by DNA microarray. J Dermatol Sci. 2012;67(1): 26-36.

DOI: 10.1016/j.jdermsci.2012.04.005.

Brenner M, Hearing VJ. The protective role of melanin against UV damage in human skin. Photochem Photobiol. 2008;84(3):539-549.

DOI: 10.1111/j.1751-1097.2007.00226.x.

Levy LL, Emer JJ. Emotional benefit of cosmetic camouflage in the treatment of facial skin conditions: personal experience and review. Clin Cosmet Investig Dermatol. 2012;5:173-182.

DOI: 10.2147/CCID.S33860.

Pillaiyar T, Manickam M, Namasivayam V. Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors. J Enzyme Inhib Med Chem. 2017;32(1):403-425.

DOI: 10.1080/14756366.2016.1256882.

Saghaie LL, Pourfarzam M, Fassihi A, Sartippour B. Synthesis and tyrosinase inhibitory properties of some novel derivatives of kojic acid. Res Pharm Sci. 2013;8(4):233-242.

Liu J, Xu X, Jiang R, Sun L, Zhao D. Vanillic acid in Panax ginseng root extract inhibits melanogenesis in B16F10 cells via inhibition of the NO/PKG signaling pathway. Biosci Biotechnol Biochem. 2019;83(7):1205-1215.

DOI: 10.1080/09168451.2019.1606694.

Eghbali Feriz S, Taleghani A, Najjar HA, Emami SA, Rahimi H, Asili J, et al. Anti-melanogenesis and anti-tyrosinase properties of Pistacia atlantica subsp. mutica extracts on B16F10 murine melanoma cells. Res Pharm Sci. 2018;13(6):533-545.

DOI: 10.4103/1735-5362.245965.

Chou ST, Chang WL, Chang CT, Hsu SL, Lin YC, Shih Y. Cinnamomum cassia essential oil inhibits alpha-MSH-induced melanin production and oxidative stress in murine B16 melanoma cells. Int J Mol Sci. 2013;14(9):19186-19201.

DOI: 10.3390/ijms140919186.

Min B, McClung AM, Chen MH. Phytochemicals and antioxidant capacities in rice brans of different color. J Food Sci. 2011;76(1):117-126.

DOI: 10.1111/j.1750-3841.2010.01929.x.

Tian S, Nakamura K, Kayahara H. Analysis of phenolic compounds in white rice, brown rice, and germinated brown rice. J Agric Food Chem. 2004;52(15):4808-4813.

DOI: 10.1021/jf049446f.

Webber DM, Hettiarachchy NS, Li R, Horax R, Theivendran S. Phenolic profile and antioxidant activity of extracts prepared from fermented heat-stabilized defatted rice bran. J Food Sci. 2014;79(11):H2383-2391.

DOI: 10.1111/1750-3841.12658.

Rodboon T, Okada S, Suwannalert P. Germinated riceberry rice enhanced protocatechuic acid and vanillic acid to suppress melanogenesis through cellular oxidant-related tyrosinase activity in B16 cells. Antioxidants (Basel). 2020;9(3):247-258.

DOI: 10.3390/antiox9030247.

Chang TS, Lin VC. Melanogenesis inhibitory activity of two generic drugs: cinnarizine and trazodone in mouse B16 melanoma cells. Int J Mol Sci. 2011;12(12):8787-8796.

DOI: 10.3390/ijms12128787.

Zaidi KU, Ali SA, Ali AS. Purified mushroom tyrosinase induced melanogenic protein expression in B16F10 melanocytes: a quantitative densitometric analysis. Open Med Chem J. 2018;12:36-47.

DOI: 10.2174/1874104501812010036.

Padilla S, Corum D, Padnos B, Hunter DL, Beam A, Houck KA. Zebrafish developmental screening of the ToxCastTM Phase I chemical library. Reprod Toxicol. 2012;33(2):174-187.

DOI: 10.1016/j.reprotox.2011.10.018.

Rana N, Moond M, Marthi A, Bapatla S, Sarvepalli T, Chatti K. Caffeine-induced effects on heart rate in zebrafish embryos and possible mechanisms of action: an effective system for experiments in chemical biology. Zebrafish. 2010;7(1):69-81.

DOI: 10.1089/zeb.2009.0631.

Lee DY, Lee J, Jeong YT, Byun GH, Kim JH. Melanogenesis inhibition activity of floralginsenoside A from Panax ginseng berry. J Ginseng Res. 2017;41(4):602-607.

DOI: 10.1016/j.jgr.2017.03.005.

Fenech M. The in vitro micronucleus technique. Mutat Res. 2000;455(1-2):81-95.

DOI: 10.1016/s0027-5107(00)00065-8.

Puchadapirom P, Himakoun L, Wongkrajang Y, Temsiririrkkul R, Peungvicha P, Kongsaktrakoon B. Assessment of mutagenic and genotoxic activity of Caesalpinia sappan L. extract by Ames test and micronucleus assay. JAASP. 2012;1(2):97-106.

Videira IFS, Moura DFL, Magina S. Mechanisms regulating melanogenesis. An Bras Dermatol. 2013;88(1):76-83.

DOI: 10.1590/s0365-05962013000100009.

Lin YT, Pao CC, Wu ST, Chang CY. Effect of different germination conditions on antioxidative properties and bioactive compounds of germinated brown rice. BioMed Res Int. 2015;2015:608761,1-11.

DOI: 10.1155/2015/608761.

Chan CF, Huang CC, Lee MY, Lin YS. Fermented broth in tyrosinase- and melanogenesis inhibition. Molecules. 2014;19(9):13122-13135.

DOI: 10.3390/molecules190913122.

Boissy RE. Melanosome transfer to and translocation in the keratinocyte. Exp Dermatol. 2003;12(S2):5-12.

DOI: 10.1034/j.1600-0625.12.s2.1.x.

Aoki Y, Saint-Germain N, Gyda M, Magner-Fink E, Lee YH, Credidio C. Sox10 regulates the development of neural crest-derived melanocytes in Xenopus. Dev Biol. 2003;259(1):19-33.

DOI: 10.1016/s0012-1606(03)00161-1.

Yao C, Jin CL, Oh IG, Park CH, Chung JH. Melia azedarach extract stimulates melanogenesis through increase of tyrosinase-related protein 1 expression in B16F10 mouse melanoma cells. Int J Mol Med. 2015;35(6):1761-1766.

DOI: 10.3892/ijmm.2015.2182.

Chen WC, Tseng TS, Hsiao NW, Lin YL, Wen ZH, Tsai CC. Discovery of highly potent tyrosinase inhibitor, T1, with significant anti-melanogenesis ability by zebrafish in vivo assay and computational molecular modeling. Sci Rep. 2015;5:7995-8002.

DOI: 10.1038/srep07995.

Kawakami A, Fisher DE. The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology. Lab Invest. 2017;97(6):649-656.

DOI: 10.1038/labinvest.2017.9.

World Health Organization. EHC240: principles and methods for the risk assessment of chemicals in food. In: Marla Sheffer, editor. Hazard identification and characterization: toxicological and human studies. Stuttgart, Germany: Wissenchaftliche Verlagsgesellschaft mbH; 2009. pp.4-76.


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