Inhibitory Effect of Ruta graveolensL. Extract on Guinea PigLiverand Bovine Milk Xanthine Oxidase Inhibitory effect of Ruta graveolenson xanthine oxidase
Iranian Journal of Pharmaceutical Sciences,
Vol. 5 No. 3 (2009),
1 July 2009
,
Page 163-170
https://doi.org/10.22037/ijps.v5.41212
Abstract
Flavonoids could serve as potent inhibitors of xanthine oxidase (XO). In the present study, the effects of Ruta graveolensL. extract and its major isolated flavonoids,quercetin and rutin, on guinea pig liver XO have been investigated. The inhibitory effects of R. graveolens, quercetin and its glycoside form, rutin, were assayed spectrophotometrically. R. graveolensextract showed moderate inhibition on XO activity. Interestingly, bovine milk and guinea pig liver XO were inhibited significantly at different ranges by either the extract or its flavonoids, whereas allopurinol acted with almost the same potency on both enzymes. Rutin inhibited the enzymes in a competitive manner, while quercetin was found to be a competitive and mixed inhibitor of guinea pig liver and bovine milk XO, respectively. In conclusion, R.graveolensextract can act as a good inhibitor of XO. Interestingly, it was shown that the inhibitory effects of flavonoids on XO could be species dependent.
Keywords:
- Flavonoids
- Quercetin
- Ruta graveolens
- Rutin
- Xanthine oxidase
How to Cite
Saeed Pirouzpanah, Mohammad R. Rashidi, Abbas Delazar, Seyed Vali Razavieh, & Ali Asghar Hamidi. (2009). Inhibitory Effect of Ruta graveolensL. Extract on Guinea PigLiverand Bovine Milk Xanthine Oxidase: Inhibitory effect of Ruta graveolenson xanthine oxidase. Iranian Journal of Pharmaceutical Sciences, 5(3), 163–170. https://doi.org/10.22037/ijps.v5.41212
References
[1]Kong D, Zhang Y, Pan X, Tan R, Cheng C.Inhibition of xanthine oxidase by liquiritigenin and isoliquiritigenin isolated from Sinofranchetia chinesis.Cell Mol Life Sci 2000; 57: 500-5.
[2]Beedham C. Molybdenum hydroxylases. In:Gorrod J, Oeschlager H, Caldwell J, (editors).Metabolism of xenobiotics. London: Taylor & Francis, 1998; pp. 51-8.
[3]Beedham C, Molybdenum hydroxylases. In:Ioannides C, (editor). Enzyme systems that metabolise drugs and other xenobiotics.Chichester: Wiley & Sons Ltd, 2002; pp. 148-77.
[4]Beedham C, Bruce S, Critchely D, Al-Tayib Y,Rance D. Species variation in hepatic aldehyde oxidase activity. Eur J Drug Metab Pharmacokinet1987; 12: 307-10.
[5]Linder N, Martelin E, Lapatto R, Raivio K. Post-translational inactivation of human xanthine oxidoreductase by oxygen under standard cell culture conditions. Am J Physiol Cell Physiol2003; 285: C48-55.
[6]Maia L, Mira L. Xanthine oxidase and aldehyde oxidase: Asimple procedure for the simultaneous purification from rat liver. Arch Biochem Biophys 2002; 400: 48-53.
[7]Halliwell B, Cutteridge M. Free radicals in biology and medicine, New York: Oxford Uiversity Press, 1999.
[8]Saksela M, Lapatto R, Raivio K. Irreversible conversion of xanthine dehydrogenase into xanthine oxidase by a mitochondrial protease.FEBS Lett 1999; 443: 117-21.
[9]Krenitsky T, Spector T, Hall W. Xanthine oxidase from human liver: Purification and characteri-zation. Arch Biochem Biophys 1986; 247: 108-19.
[10]Van Scoik K, Johnson C, Porter W. The pharmacology and metabolism of the thiopurine drugs 6-mercaptopurine and azathioprine. Drug Metab Rev 1985; 16: 157-74.
[11]Tapner M, Jones B, Wu W, Farrell G. Toxicity of low dose azathioprine and 6-mercaptopurine in rat hepatocytes. Roles of xanthine oxidase and mitochondrial injury. J Hepatol 2004; 40: 454-63.
[12]Yamamoto T, Moriwaki Y, Suda M, Nasako Y,Takahashi S, Hiroishi K, Nakano T, Hada T,Higashino K. Effect of BOF-4272 on the oxidation of allopurinol and pyrazinamide in vivo. Is xanthine dehydrogenase or aldehyde oxidasemore important in oxidizing both allopurinol and pyrazinamide. Biochem Pharmacol 1993; 46:2277-84.
[13]Krenitsky T, Hall W, De Miranda P, BeauchampL, Schaeffer H, Whiteman P. 6-Deoxyacyclovir:Axanthine oxidase-activated prodrug of acyclovir.Proc Natl Acad SciUSA1984; 81: 3209-13.
[14]Cotelle N. Role of flavonoids in oxidative stress.Current Topics Med Chem2001; 1: 569-90.
[15]Kitamura S, Sugihara K, Ohta S. Drug-metabolizing ability of molybdenum hydroxylases. Drug Metab Pharmacokinet2006;21: 83-98.
[16]Lin C, Chen S, Chen C, Liang Y, Lin J. Molecular modeling of flavonoids that inhibits xanthine oxidase. Biochem Biophys Res Commun2002;294: 167-72.
[17]Jiao R, Ge H, Shi D H, Tan R. An apigenin-derived xanthine oxidase inhibitor from Palhinhaea cernua. J Nat Prod 2006; 69: 1089-91.
[18]Aucamp J, Gaspar A, Hara Y. Inhibition of xanthine oxidase by catechins from tea (Camellia sinesis). Anticancer Res1997; 17: 4381-6.
[19]Owen P, Johns T. Xanthine oxidase inhibitory activity of northeastern North American plant remedies used for gout. J Ethnopharmacol1999;64: 149-60.
[20]Cos P, Ying L, Calomme M, Hu J, Cimanga K, VanPoel B, Pieters L, Vlietinck A, Van den Berghe D.Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod1998; 61: 71-6.
[21]Middleton J, Chithan K, Theoharides C. The effect of flavonoids on mammalian cells:Implication for inflammation, heart disease and cancer. Pharmacol Rev2000; 52: 673-751.
[22]Selloum L, Reichl S, Muller M, Sebihi L, Arnhold J. Effect of flavonols on the generation of superoxide anions radicals by xanthine oxidase stimulated neutrophils. Arch Biochem Biophys 2001; 395: 49-56.
[23]Van Hoorn E, Nijveldt R, Van Leeuwen P, Hofman Z, Rabet L, De Bont D, Van Norren K. Accurate prediction of xanthine oxidase inhibition based on the structure of flavonoids. Eur J Pharmacol 2002; 451: 111-8.[24]Zhu J, Wang Y, Kong L, Yang C, Zhang X. Effects of Biota orientalisextract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. J Ethnopharmacol 2004; 93: 133-40.
[25]Nagao A, Seki M, Kobayashi H. Inhibition of xanthine oxidase by flavonoids. Biosci Biotechnol Biochem1999; 63: 1787-90.
[26]Nijveldt R, Van Nood E, Van Hoorn E, Boelens P, Van Norren K, Van Leeuwen P. Flavonoids: Areview of probable mechanisms of action and potential application. Am J Clin Nutr2001; 74:418-25.
[27]Beedham C, Critchley D, Rance D. Substrate specificity of human liver aldehyde oxidase toward substituted quinazolines and phthalazines:Acomparison with hepatic enzyme from guinea pig, rabbit, and baboon. Arch Biochem Biophys1995; 319: 481-90.
[28]Skidmore-Roth L., Mosby's handbook of herbs and natural supplements. St. Louis: Mosby, 2001.
[29]Duke J, Bogenschutz- Godwin M, Du Cellier J,Duke P, Handbook of medicinal herbs. Boca Raton: CRC press, 2002.
[30]Pirouzpanah S, Rashidi M, Delazar A, Razavieh S, Hamidi A. Inhibitory effects of Ruta graveolens L. extract on guinea pig liver aldehyde oxidase.Chem Pharm Bull2006; 54: 9-13.
[31]Pirouzpanah S, Hanaee J, Razavieh S, Rashidi M.Inhibitory effects of flavonoids on aldehyde oxidase activity. J Enzyme Inhib Med Chem 2008;24: 14-21.
[32]Breitmaier E, Voelter W., Carbon- 13 NMR spectroscopy. New York: VCH Verlagsgesellschaft mbH, 1989.
[33]Mabry T, Markham K, Thomas M, The systematicidentific ation of flavonoids. New York: Spring-Verlag, 1970.
[34]Johnson C, Stubley-Beedham C, Stell J.Hydralazine: Apotent inhibitor of aldehyde oxidase activity in vitroand in vivo. Biochem Pharmacol1985; 15: 4251-6.
[35]Marangoni A, Enzyme kinetics, a modern approach. New Jersey: John Wiley, 2003.
[36]Smith P, Krohn R, Hermanson G, Mallia A,Gartner F, Provenzano M, Fujimoto E, Goeke N, Olson B, Klenk D. Measurement of protein using bicinchoninic acid. Anal Biochem1985;150: 76-85.
[37]Judge A, Dodd S. Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication. Am J Physiol Heart Circ Physiol 2004; 286: H252-6.
[38]Dew T, Day A, Morgan R. Xanthine oxidase activity in vitro: Effects of food extracts and components. J Agric Food Chem2005; 53: 6510-5.
[39]Obach R. Potent inhibition of human liver aldehyde oxidase by raloxifene. Drug Metab Dispos2004; 32: 89-97.
[2]Beedham C. Molybdenum hydroxylases. In:Gorrod J, Oeschlager H, Caldwell J, (editors).Metabolism of xenobiotics. London: Taylor & Francis, 1998; pp. 51-8.
[3]Beedham C, Molybdenum hydroxylases. In:Ioannides C, (editor). Enzyme systems that metabolise drugs and other xenobiotics.Chichester: Wiley & Sons Ltd, 2002; pp. 148-77.
[4]Beedham C, Bruce S, Critchely D, Al-Tayib Y,Rance D. Species variation in hepatic aldehyde oxidase activity. Eur J Drug Metab Pharmacokinet1987; 12: 307-10.
[5]Linder N, Martelin E, Lapatto R, Raivio K. Post-translational inactivation of human xanthine oxidoreductase by oxygen under standard cell culture conditions. Am J Physiol Cell Physiol2003; 285: C48-55.
[6]Maia L, Mira L. Xanthine oxidase and aldehyde oxidase: Asimple procedure for the simultaneous purification from rat liver. Arch Biochem Biophys 2002; 400: 48-53.
[7]Halliwell B, Cutteridge M. Free radicals in biology and medicine, New York: Oxford Uiversity Press, 1999.
[8]Saksela M, Lapatto R, Raivio K. Irreversible conversion of xanthine dehydrogenase into xanthine oxidase by a mitochondrial protease.FEBS Lett 1999; 443: 117-21.
[9]Krenitsky T, Spector T, Hall W. Xanthine oxidase from human liver: Purification and characteri-zation. Arch Biochem Biophys 1986; 247: 108-19.
[10]Van Scoik K, Johnson C, Porter W. The pharmacology and metabolism of the thiopurine drugs 6-mercaptopurine and azathioprine. Drug Metab Rev 1985; 16: 157-74.
[11]Tapner M, Jones B, Wu W, Farrell G. Toxicity of low dose azathioprine and 6-mercaptopurine in rat hepatocytes. Roles of xanthine oxidase and mitochondrial injury. J Hepatol 2004; 40: 454-63.
[12]Yamamoto T, Moriwaki Y, Suda M, Nasako Y,Takahashi S, Hiroishi K, Nakano T, Hada T,Higashino K. Effect of BOF-4272 on the oxidation of allopurinol and pyrazinamide in vivo. Is xanthine dehydrogenase or aldehyde oxidasemore important in oxidizing both allopurinol and pyrazinamide. Biochem Pharmacol 1993; 46:2277-84.
[13]Krenitsky T, Hall W, De Miranda P, BeauchampL, Schaeffer H, Whiteman P. 6-Deoxyacyclovir:Axanthine oxidase-activated prodrug of acyclovir.Proc Natl Acad SciUSA1984; 81: 3209-13.
[14]Cotelle N. Role of flavonoids in oxidative stress.Current Topics Med Chem2001; 1: 569-90.
[15]Kitamura S, Sugihara K, Ohta S. Drug-metabolizing ability of molybdenum hydroxylases. Drug Metab Pharmacokinet2006;21: 83-98.
[16]Lin C, Chen S, Chen C, Liang Y, Lin J. Molecular modeling of flavonoids that inhibits xanthine oxidase. Biochem Biophys Res Commun2002;294: 167-72.
[17]Jiao R, Ge H, Shi D H, Tan R. An apigenin-derived xanthine oxidase inhibitor from Palhinhaea cernua. J Nat Prod 2006; 69: 1089-91.
[18]Aucamp J, Gaspar A, Hara Y. Inhibition of xanthine oxidase by catechins from tea (Camellia sinesis). Anticancer Res1997; 17: 4381-6.
[19]Owen P, Johns T. Xanthine oxidase inhibitory activity of northeastern North American plant remedies used for gout. J Ethnopharmacol1999;64: 149-60.
[20]Cos P, Ying L, Calomme M, Hu J, Cimanga K, VanPoel B, Pieters L, Vlietinck A, Van den Berghe D.Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod1998; 61: 71-6.
[21]Middleton J, Chithan K, Theoharides C. The effect of flavonoids on mammalian cells:Implication for inflammation, heart disease and cancer. Pharmacol Rev2000; 52: 673-751.
[22]Selloum L, Reichl S, Muller M, Sebihi L, Arnhold J. Effect of flavonols on the generation of superoxide anions radicals by xanthine oxidase stimulated neutrophils. Arch Biochem Biophys 2001; 395: 49-56.
[23]Van Hoorn E, Nijveldt R, Van Leeuwen P, Hofman Z, Rabet L, De Bont D, Van Norren K. Accurate prediction of xanthine oxidase inhibition based on the structure of flavonoids. Eur J Pharmacol 2002; 451: 111-8.[24]Zhu J, Wang Y, Kong L, Yang C, Zhang X. Effects of Biota orientalisextract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. J Ethnopharmacol 2004; 93: 133-40.
[25]Nagao A, Seki M, Kobayashi H. Inhibition of xanthine oxidase by flavonoids. Biosci Biotechnol Biochem1999; 63: 1787-90.
[26]Nijveldt R, Van Nood E, Van Hoorn E, Boelens P, Van Norren K, Van Leeuwen P. Flavonoids: Areview of probable mechanisms of action and potential application. Am J Clin Nutr2001; 74:418-25.
[27]Beedham C, Critchley D, Rance D. Substrate specificity of human liver aldehyde oxidase toward substituted quinazolines and phthalazines:Acomparison with hepatic enzyme from guinea pig, rabbit, and baboon. Arch Biochem Biophys1995; 319: 481-90.
[28]Skidmore-Roth L., Mosby's handbook of herbs and natural supplements. St. Louis: Mosby, 2001.
[29]Duke J, Bogenschutz- Godwin M, Du Cellier J,Duke P, Handbook of medicinal herbs. Boca Raton: CRC press, 2002.
[30]Pirouzpanah S, Rashidi M, Delazar A, Razavieh S, Hamidi A. Inhibitory effects of Ruta graveolens L. extract on guinea pig liver aldehyde oxidase.Chem Pharm Bull2006; 54: 9-13.
[31]Pirouzpanah S, Hanaee J, Razavieh S, Rashidi M.Inhibitory effects of flavonoids on aldehyde oxidase activity. J Enzyme Inhib Med Chem 2008;24: 14-21.
[32]Breitmaier E, Voelter W., Carbon- 13 NMR spectroscopy. New York: VCH Verlagsgesellschaft mbH, 1989.
[33]Mabry T, Markham K, Thomas M, The systematicidentific ation of flavonoids. New York: Spring-Verlag, 1970.
[34]Johnson C, Stubley-Beedham C, Stell J.Hydralazine: Apotent inhibitor of aldehyde oxidase activity in vitroand in vivo. Biochem Pharmacol1985; 15: 4251-6.
[35]Marangoni A, Enzyme kinetics, a modern approach. New Jersey: John Wiley, 2003.
[36]Smith P, Krohn R, Hermanson G, Mallia A,Gartner F, Provenzano M, Fujimoto E, Goeke N, Olson B, Klenk D. Measurement of protein using bicinchoninic acid. Anal Biochem1985;150: 76-85.
[37]Judge A, Dodd S. Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication. Am J Physiol Heart Circ Physiol 2004; 286: H252-6.
[38]Dew T, Day A, Morgan R. Xanthine oxidase activity in vitro: Effects of food extracts and components. J Agric Food Chem2005; 53: 6510-5.
[39]Obach R. Potent inhibition of human liver aldehyde oxidase by raloxifene. Drug Metab Dispos2004; 32: 89-97.
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