Keywords
How to Cite
Abstract
Background: Cosmos caudatus (Ulam Raja) is an appetizer (ulam) eaten with rice in Malaysia. Previous studies showed that Cosmos caudatus possess high antioxidant content. Nrf2 is a transcription factor which regulates the expression of phase II enzymes and antioxidant proteins. The aim of this study is to investigate the effects of Cosmos caudatus aqueous extract (UR) on the expression of Nrf2 target genes in mice liver.
Methods: ICR white mice were treated for 21 days with different doses of UR (100, 500, 1000 mg/kg) through oral gavage. Control mice were only given distilled water. After 21 days, the mice were sacrificed and their livers harvested. Total RNA was extracted, reverse transcribed and subjected to qPCR to detect Nrf2 target genes expression.
Results: Administration of 100 mg/kg UR significantly increased NQO1 expression in mice liver. Administration of 500 mg/kg UR significantly increased HO-1 liver expression. Administration of 100 and 500 mg/kg UR significantly increased GSTA1 liver expression. Administration of 500 and 1000 mg/kg UR significantly increased GSTM3 liver expression, whereas GSTP and GSTM1 liver expression was significantly decreased at similar doses. Administration of all doses of UR significantly decreased the expression of GSTA3, SOD3 and GCLC in mice liver.
Conclusion: UR administration mostly resulted in downregulation of Nrf2 target genes. However, conclusive evidence can only be made through the use of Nrf2 knockout mice or by performing Nrf2 nuclear translocation studies.
References
Samy J, Sugumaran M, Lee KLW. Herbs of Malaysia: An introduction to the medicinal, culinary, aromatic and cosmetic use of herbs. 1st ed. Kuala Lumpur: Times Editions; 2005.
Bodeker G. Health and beauty from the rainforest: Malaysian traditions of ramuan. 1st ed. Kuala Lumpur: Didier Millet; 2009.
Hassan W. Healing herbs of Malaysia. 1st ed. Kuala Lumpur: Federal Land Development Agency; 2006.
Abas F, Lajis NH, Israf D, Khozirah S, Kalsom YU. Antioxidant and nitric oxide inhibition activities of selected Malay traditional vegetables. Food Chem 2006; 95(4): 566-73. https://doi.org/10.1016/j.foodchem.2005.01.034
Wong SP, Leong LP, Koh JHW. Antioxidant activities of aqueous extracts of selected plants. Food Chem 2006; 99(4): 775-83. https://doi.org/10.1016/j.foodchem.2005.07.058
Mustafa R, Hamid AA, Mohamed S, Bakar FA. Total phenolic compounds, flavonoids, and radical scavenging activity of 21 selected tropical plants. J Food Sci 2010; 75(1): C28-C35. https://doi.org/10.1111/j.1750-3841.2009.01401.x
Reihani SFS, Azhar ME. Antioxidant activity and total phenolic content in aqueous extracts of selected traditional Malay salads (Ulam). Int Food Res J 2012; 19: 1439-44.
Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013; 53: 401-26. https://doi.org/10.1146/annurev-pharmtox-011112-140320
Abdullah A, Dhaliwal KK, Roslan NNF, Lee CH, Kalaiselvam M, Radman HM, Saad QHM, Yusof K, Jaarin K. The effects of Cosmos caudatus (ulam raja) on detoxifying enzymes in extrahepatic organs in mice. Journal of Applied Pharmaceutical Science 2015; 5(1): 082-088. https://doi.org/10.7324/JAPS.2015.50115
Radman HM, Yusof K, Saad QHM, Wan-Ngah WZ, Abdullah A. The effect of Ulam Raja (Cosmos caudatus) on drug metabolizing enzymes, lipid peroxidation and antioxidant status in mice liver. Int J PharmTech Res 2014; 6(4):1213-25.
Dinkova-Kostova AT. Chemoprotection against cancer: an idea whose time has come. Altern Ther Health Med 2007; 13(2): S122-7.
Kong L, Tanito M, Huang Z, Li F, Zhou X, Zaharia A, Yodoi J, Mcginnis JF, Cao W. Delay of photoreceptor degeneration in tubby mouse by sulforaphane. J Neurochem 2007; 101(4): 1041-52. https://doi.org/10.1111/j.1471-4159.2007.04481.x
Leung L, Kwong M, Hou S, Lee C, Chan JY. Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress. J Biol Chem 2003; 278(48): 48021-29. https://doi.org/10.1074/jbc.M308439200
Xu Z, Chen L, Leung L, Yen TB, Lee C, & Chan JY. Liver-specific inactivation of the Nrf1 Gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia. Proc Natl Acad Sci USA 2005; 102(11): 4120-25. https://doi.org/10.1073/pnas.0500660102
Seta F, Rahmani M, Turner PV, Funk CD. Pulmonary oxidative stress is increased in cyclooxygenase-2 knockdown mice with mild pulmonary hypertension induced by monocrotaline. PLoS ONE 2011; 6(8): e23439. https://doi.org/10.1371/journal.pone.0023439
Lu H, Koshkin V, Allister EM, Gyulkhandanyan AV, Wheeler MB. Molecular and metabolic evidence for mitochondrial defects associated with ?-Cell dysfunction in a mouse model of type 2 diabetes. Diabetes 2010; 59(2): 448-59. https://doi.org/10.2337/db09-0129
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2? ??CT method. Methods 2001; 25(4): 402-8. https://doi.org/10.1006/meth.2001.1262
Ong YL, Irvine A. Quantitative real-time PCR: a critique of method and practical considerations. Hematology 2002; 7(1): 59-67. https://doi.org/10.1080/10245330290015573
Katzung BG, Masters SB, Trevor AJ. Basic & clinical pharmacology. 13th ed. New York: McGraw-Hill Medical; 2014.
Higgins LG, Hayes JD. Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agents. Drug Metab Rev 2011; 43(2): 92-137. https://doi.org/10.3109/03602532.2011.567391
Sukrasno S, Fidriany I, Anggadiredja K, Handayani WA, Anam K. Influence of drying method on flavonoid content of Cosmos caudatus (Kunth) leaves. Res J Med Plant 2011; 5(2): 189-95. https://doi.org/10.3923/rjmp.2011.189.195
Andarwulan N, Kurniasih D, Apriady RA, Rahmat H, Roto AV, Bolling BW. Polyphenols, carotenoids, and ascorbic acid in underutilized medicinal vegetables. J Funct Foods 2012; 4(1): 339-47. https://doi.org/10.1016/j.jff.2012.01.003
Iverson F. In vivo studies on buthylated hydroxyanisole. Food Chem Toxicol 1999; 37: 993-7. https://doi.org/10.1016/S0278-6915(99)00091-5
Singh RP, Padmavathi B, Rao AR. Modulatory influence of Adhatoda vesica (Justicia adhatoda) leaf extract on the enzymes of xenobiotic metabolism, antioxidant status and lipid peroxidation in mice. Mol Cell Biochem 2000; 213(1-2): 99-109.
Aleksunes LM, Goedken M, Manautou JE. Up-Regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury. World J Gastroenterol 2006; 12(12): 1937-40. https://doi.org/10.3748%2Fwjg.v12.i12.1937
Dinkova-Kostova AT, Talalay P. Persuasive evidence that quinone reductase type 1 (DT-diaphorase) protects cells against the toxicity of electrophiles and reactive forms of oxygen. Free Radic Biol Med 2000; 29(3): 231-40. https://doi.org/10.1016/S0891-5849(00)00300-2
Singh B, Bhat HK. Superoxide dismutase 3 is induced by antioxidants, inhibits oxidative DNA damage and is associated with inhibition of estrogen-induced breast cancer. Carcinogenesis 2012; 33(12): 2601-10. https://doi.org/10.1093/carcin/bgs300
Weidinger A, Kozlov AV. Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction. Biomolecules 2015; 5(2): 472-84. https://doi.org/10.3390/biom5020472
Agarwal A, Bolisetty S. Adaptive responses to tissue injury: Role of heme oxygenase-1. Trans Am Clin Climatol Assoc 2013; 124: 111-22.
Chung SW, Hall SR, Perrella MA. Role of haem oxygenase?1 in microbial host defence. Cell Microbiol 2009; 11(2): 199-207. https://doi.org/10.1111%2Fj.1462-5822.2008.01261.x
Farombi EO, Surh Y-J. Heme oxygenase-1 as a potential therapeutic target for hepatoprotection. BMB Reports 2006; 39(5): 479-91. https://doi.org/10.5483/BMBRep.2006.39.5.479
Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol 2010; 50: 323-54. https://doi.org/10.1146/annurev.pharmtox.010909.105600
Pae H-O, Chung H-T. Heme oxygenase-1: its therapeutic roles in inflammatory diseases. Immune Netw 2009; 9(1): 12-19. https://doi.org/10.4110/in.2009.9.1.12
Chau L-Y. Heme oxygenase-1: emerging target of cancer therapy. J Biomed Sci 2015; 22: 22 (7 pages). https://doi.org/10.1186/s12929-015-0128-0
Yang H, Magilnick N, Lee C, Kalmaz D, Ou X, Chan JY, Lu SC. Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-kappaB and AP-1. Mol Cell Biol 2005; 25(14): 5933-46. https://doi.org/10.1128/MCB.25.14.5933-5946.2005
Lee TK, Vairappan CS. Antioxidant, antibacterial and cytotoxic activities of essential oils and ethanol extracts of selected South East Asian herbs. J Med Plants Res 2011; 5(21): 5284-90.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright (c) 2017 Azman Abdullah, Tan Chung Phern, Nur Fatihah Hanis Mohamad Rahim, Nur Izzati Zaharuddin, Nurdayana Maulat Salihin, Ahmad Hilmi Yusof, Kamsiah Jaarin, Yusof Kamisah, Qodriyah Haji Mohd Saad, Nur Azlina Mohd Fahami and Harizz Miszard Radman