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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

In vitro and in silico Xanthine Oxidase Inhibitory Activity of Selected Phytochemicals Widely Present in Various Edible Plants

Author(s): Arshad Mehmood, Ashfaq Ur Rehman, Muhammad Ishaq, Liang Zhao, Jiayi Li, Muhammad Usman, Lei Zhao*, Abdur Rehman, Oumeddour D. Zad and Chengtao Wang*

Volume 23, Issue 9, 2020

Page: [917 - 930] Pages: 14

DOI: 10.2174/1386207323666200428075224

Price: $65

Abstract

Aim and Objective: The present study was designed to evaluate the xanthine oxidase (XO) inhibitory and antioxidant activities of 30 bioactive compounds present in edible food plants for the possible treatment of hyperuricemia.

Materials and Methods: The XO inhibitory, SO and DPPH radical scavenging activities of selected dietary polyphenols were determined by using colorimetric assays. The molecular docking analysis was performed to evaluate the insight into inhibitory mode of action of bioactive compounds against XO.

Results: The results show that apigenin, galangin, kaempferol, quercetin, genistein and resveratrol potently inhibit XO enzyme among all tested compounds. Flavonoids exhibit higher, anthocyanins and hydroxycinnamic acids moderate, maslinic acid, ellagic acid, salicylic acid, [6]-gingerol and flavan-3-ols showed weak XO inhibitory activity. The results of molecular docking study revealed that these bioactive compounds bind with the active site of XO and occupy the active site which further prevents the entrance of substrate and results in the inhibition of XO.

Conclusion: Inhibition of XO gives a robust biochemical basis for management of hyperuricemia, gout and other associated diseases via controlling uric acid synthesis.

Keywords: Xanthine oxidase, hyperuricemia, gout, antioxidant activities, phytochemicals, bioactive compounds.

[1]
Lü, J.M.; Yao, Q.; Chen, C. 3,4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a potent inhibitor of xanthine oxidase: a potential therapeutic agent for treatment of hyperuricemia and gout. Biochem. Pharmacol., 2013, 86(9), 1328-1337.
[http://dx.doi.org/10.1016/j.bcp.2013.08.011] [PMID: 23994369]
[2]
Marcolongo, R. Gout: the king of diseases and the disease of kings. J. Siena Academy of Sci., 2012, 4(1), 7-17.
[http://dx.doi.org/10.4081/jsas.2012.7]
[3]
Borges, F.; Fernandes, E.; Roleira, F. Progress towards the discovery of xanthine oxidase inhibitors. Curr. Med. Chem., 2002, 9(2), 195-217.
[http://dx.doi.org/10.2174/0929867023371229] [PMID: 11860355]
[4]
Kumar, R.; Joshi, G.; Kler, H.; Kalra, S.; Kaur, M.; Arya, R. Toward an understanding of structural insights of xanthine and aldehyde oxidases: An overview of their inhibitors and role in various diseases. Med. Res. Rev., 2018, 38(4), 1073-1125.
[http://dx.doi.org/10.1002/med.21457] [PMID: 28672082]
[5]
Mehmood, A.; Zhao, L.; Wang, C.; Nadeem, M.; Raza, A.; Ali, N.; Shah, A.A. Management of hyperuricemia through dietary polyphenols as a natural medicament: A comprehensive review. Crit. Rev. Food Sci. Nutr., 2019, 59(9), 1433-1455.
[http://dx.doi.org/10.1080/10408398.2017.1412939] [PMID: 29278921]
[6]
Mehmood, A. Ishaq, M.; Zhao, L.; Safdar, B.; Rehman, A.U.; Munir, M.; Raza, A.; Nadeem, M.; Iqbal, W.; Wang, C. Natural Compounds with xanthine oxidase inhibitory activity: A review. Chem. Biol. Drug Des., 2019, 93, 387-418.
[http://dx.doi.org/10.1111/cbdd.13437]
[7]
Harrison, R. Structure and function of xanthine oxidoreductase: where are we now? Free Radic. Biol. Med., 2002, 33(6), 774-797.
[http://dx.doi.org/10.1016/S0891-5849(02)00956-5] [PMID: 12208366]
[8]
Arellano, F.; Sacristán, J.A. Allopurinol hypersensitivity syndrome: a review. Ann. Pharmacother., 1993, 27(3), 337-343.
[http://dx.doi.org/10.1177/106002809302700317] [PMID: 8453174]
[9]
Nile, S.H.; Nile, A.S.; Keum, Y.S.; Sharma, K. Utilization of quercetin and quercetin glycosides from onion (Allium cepa L.) solid waste as an antioxidant, urease and xanthine oxidase inhibitors. Food Chem., 2017, 235, 119-126.
[http://dx.doi.org/10.1016/j.foodchem.2017.05.043] [PMID: 28554615]
[10]
Nile, S.H.; Keum, Y.S.; Nile, A.S.; Kwon, Y.D.; Kim, D.H. Potential cow milk xanthine oxidase inhibitory and antioxidant activity of selected phenolic acid derivatives. J. Biochem. Mol. Toxicol., 2018, 32(1), e22005.
[http://dx.doi.org/10.1002/jbt.22005] [PMID: 29071757]
[11]
Zhang, Z.C.; Wang, H.B.; Zhou, Q.; Hu, B.; Wen, J.H.; Zhang, J.L. Screening of effective xanthine oxidase inhibitors in dietary anthocyanins from purple sweet potato (Ipomoea batatas L. Cultivar Eshu No. 8) and deciphering of the underlying mechanisms in vitro. J. Funct. Foods, 2017, 36, 102-111.
[http://dx.doi.org/10.1016/j.jff.2017.06.048]
[12]
Zhang, C.; Wang, R.; Zhang, G.; Gong, D. Mechanistic insights into the inhibition of quercetin on xanthine oxidase. Int. J. Biol. Macromol., 2018, 112, 405-412.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.01.190] [PMID: 29410028]
[13]
Qian, X.; Wang, X.; Luo, J.; Liu, Y.; Pang, J.; Zhang, H.; Xu, Z.; Xie, J.; Jiang, X.; Ling, W. Hypouricemic and nephroprotective roles of anthocyanins in hyperuricemic mice. Food Funct., 2019, 10(2), 867-878.
[http://dx.doi.org/10.1039/C8FO02124D] [PMID: 30693917]
[14]
Nile, S.H.; Park, S.W. Chromatographic analysis, antioxidant, anti-inflammatory, and xanthine oxidase inhibitory activities of ginger extracts and its reference compounds. Ind. Crops Prod., 2015, 70, 238-244.
[http://dx.doi.org/10.1016/j.indcrop.2015.03.033]
[15]
Nile, S.H.; Park, S.W. Total phenolics, antioxidant and xanthine oxidase inhibitory activity of three colored onions (Allium cepa L.). Front. Life Sci., 2013, 7(3-4), 224-228.
[http://dx.doi.org/10.1080/21553769.2014.901926]
[16]
Mehmood, A.; Ishaq, M.; Zhao, L.; Yaqoob, S.; Safdar, B.; Nadeem, M.; Munir, M.; Wang, C. Impact of ultrasound and conventional extraction techniques on bioactive compounds and biological activities of blue butterfly pea flower (Clitoria ternatea L.). Ultrason. Sonochem., 2019, 51(51), 12-19.
[http://dx.doi.org/10.1016/j.ultsonch.2018.10.013] [PMID: 30514481]
[17]
Mehmood, A.; Zhao, L.; Ishaq, M.; Safdar, B.; Wang, C.; Nadeem, M. Optimization of total phenolic contents, antioxidant, and in-vitro xanthine oxidase inhibitory activity of sunflower head. CYTA J. Food, 2018, 16(1), 957-964.
[http://dx.doi.org/10.1080/19476337.2018.1504121]
[18]
Bravo, L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr. Rev., 1998, 56(11), 317-333.
[http://dx.doi.org/10.1111/j.1753-4887.1998.tb01670.x] [PMID: 9838798]
[19]
Williams, R.J.; Spencer, J.P.; Rice-Evans, C. Flavonoids: antioxidants or signalling molecules? Free Radic. Biol. Med., 2004, 36(7), 838-849.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.01.001] [PMID: 15019969]
[20]
Harborne, J.B.; Baxter, H. The Handbook of Natural Flavonoids; JohnWiley and Sons, 1999, pp. 1-2.
[21]
González-Castejón, M.; Rodriguez-Casado, A. Dietary phytochemicals and their potential effects on obesity: a review. Pharmacol. Res., 2011, 64(5), 438-455.
[http://dx.doi.org/10.1016/j.phrs.2011.07.004] [PMID: 21798349]
[22]
Lin, L.; Yang, Q.; Zhao, K.; Zhao, M. Identification of the free phenolic profile of Adlay bran by UPLC-QTOF-MS/MS and inhibitory mechanisms of phenolic acids against xanthine oxidase. Food Chem., 2018, 253, 108-118.
[http://dx.doi.org/10.1016/j.foodchem.2018.01.139] [PMID: 29502809]
[23]
Zhang, C.; Zhang, G.; Pan, J.; Gong, D. Galangin competitively inhibits xanthine oxidase by a ping-pong mechanism. Food Res. Int., 2016, 89(Pt 1), 152-160.
[http://dx.doi.org/10.1016/j.foodres.2016.07.021] [PMID: 28460900]
[24]
Molecular Operating Environment (MOE) 2016.08. Chemical Computing Group Inc 1010 Sherbrooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7 2016.
[25]
Rasouli, H.; Farzaei, M.H.; Mansouri, K.; Mohammadzadeh, S.; Khodarahmi, R. Plant cell cancer: may natural phenolic compounds prevent onset and development of plant cell malignancy? A literature review. Molecules, 2016, 21(9), 1104.
[http://dx.doi.org/10.3390/molecules21091104] [PMID: 27563858]
[26]
Croft, K.D. Dietary polyphenols: Antioxidants or not? Arch. Biochem. Biophys., 2016, 595, 120-124.
[http://dx.doi.org/10.1016/j.abb.2015.11.014] [PMID: 27095227]
[27]
Lima, G.P.P.; Vianello, F.; Corrêa, C.R.; Campos, R.A.D.S.; Borguini, M.G. Polyphenols in fruits and vegetables and its effect on human health. Food Nutr. Sci., 2014, 1065-1082.
[http://dx.doi.org/10.4236/fns.2014.511117]
[28]
Yan, J.; Zhang, G.; Hu, Y.; Ma, Y. Effect of luteolin on xanthine oxidase: inhibition kinetics and interaction mechanism merging with docking simulation. Food Chem., 2013, 141(4), 3766-3773.
[http://dx.doi.org/10.1016/j.foodchem.2013.06.092] [PMID: 23993547]
[29]
Wang, Y.; Zhang, G.; Pan, J.; Gong, D. Novel insights into the inhibitory mechanism of kaempferol on xanthine oxidase. J. Agric. Food Chem., 2015, 63(2), 526-534.
[http://dx.doi.org/10.1021/jf505584m] [PMID: 25539132]
[30]
Hayashi, T.; Sawa, K.; Kawasaki, M.; Arisawa, M.; Shimizu, M.; Morita, N. Inhibition of cow’s milk xanthine oxidase by flavonoids. J. Nat. Prod., 1988, 51(2), 345-348.
[http://dx.doi.org/10.1021/np50056a030] [PMID: 3379415]
[31]
Lin, S.; Zhang, G.; Liao, Y.; Pan, J.; Gong, D. Dietary flavonoids as xanthine oxidase inhibitors: Structure–affinity and structure–activity relationships. ‎. J. Agric. Food Chem., 2015, 63(35), 7784-7794.
[http://dx.doi.org/10.1021/acs.jafc.5b03386] [PMID: 26285120]
[32]
Masuoka, N.; Matsuda, M.; Kubo, I. Characterization of the antioxidant activity of flavonoids. Food Chem., 2012, 131(2), 541-545.
[http://dx.doi.org/10.1016/j.foodchem.2011.09.020]
[33]
Kanbay, M.; Jensen, T.; Solak, Y.; Le, M.; Roncal-Jimenez, C.; Rivard, C.; Lanaspa, M.A.; Nakagawa, T.; Johnson, R.J. Uric acid in metabolic syndrome: From an innocent bystander to a central player. Eur. J. Intern. Med., 2016, 29, 3-8.
[http://dx.doi.org/10.1016/j.ejim.2015.11.026] [PMID: 26703429]
[34]
Sun, K.; Fan, J.; Han, J. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage. Acta Pharm. Sin. B, 2015, 5(1), 8-24.
[http://dx.doi.org/10.1016/j.apsb.2014.11.002] [PMID: 26579420]
[35]
Soltani, Z.; Rasheed, K.; Kapusta, D.R.; Reisin, E. Potential role of uric acid in metabolic syndrome, hypertension, kidney injury, and cardiovascular diseases: is it time for reappraisal? Curr. Hypertens. Rep., 2013, 15(3), 175-181.
[http://dx.doi.org/10.1007/s11906-013-0344-5] [PMID: 23588856]
[36]
Borghi, C.; Desideri, G. Urate-lowering drugs and prevention of cardiovascular disease: the emerging role of xanthine oxidase inhibition. Hypertension, 2016, 67(3), 496-498.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.06531] [PMID: 26865197]
[37]
Viazzi, F.; Garneri, D.; Leoncini, G.; Gonnella, A.; Muiesan, M.L.; Ambrosioni, E.; Costa, F.V.; Leonetti, G.; Pessina, A.C.; Trimarco, B.; Volpe, M.; Agabiti Rosei, E.; Deferrari, G.; Pontremoli, R. Serum uric acid and its relationship with metabolic syndrome and cardiovascular risk profile in patients with hypertension: insights from the I-DEMAND study. Nutr. Metab. Cardiovasc. Dis., 2014, 24(8), 921-927.
[http://dx.doi.org/10.1016/j.numecd.2014.01.018] [PMID: 24675005]
[38]
Hayyan, M.; Hashim, M.A.; AlNashef, I.M. Superoxide ion: generation and chemical implications. Chem. Rev., 2016, 116(5), 3029-3085.
[http://dx.doi.org/10.1021/acs.chemrev.5b00407] [PMID: 26875845]
[39]
Enroth, C.; Eger, B.T.; Okamoto, K.; Nishino, T.; Nishino, T.; Pai, E.F. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc. Natl. Acad. Sci. USA, 2000, 97(20), 10723-10728.
[http://dx.doi.org/10.1073/pnas.97.20.10723] [PMID: 11005854]
[40]
Cos, P.; Ying, L.; Calomme, M.; Hu, J.P.; Cimanga, K.; Van Poel, B.; Pieters, L.; Vlietinck, A.J.; Vanden Berghe, D. Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J. Nat. Prod., 1998, 61(1), 71-76.
[http://dx.doi.org/10.1021/np970237h] [PMID: 9461655]
[41]
Li, B.; Li, Y.; Hu, Q. Antioxidant activity of flavonoids from tartary buckwheat bran. Toxicol. Environ. Chem., 2016, 98(3-4), 429-438.
[http://dx.doi.org/10.1080/02772248.2015.1123486]
[42]
Zhang, C.; Zhang, G.; Liao, Y.; Gong, D. Myricetin inhibits the generation of superoxide anion by reduced form of xanthine oxidase. Food Chem., 2017, 221, 1569-1577.
[http://dx.doi.org/10.1016/j.foodchem.2016.10.136] [PMID: 27979130]
[43]
Da Silva, S.L.; Da Silva, A.; Honório, K.M.; Marangoni, S.; Toyama, M.H.; Da Silva, A.B.F. The influence of electronic, steric and hydrophobic properties of flavonoid compounds in the inhibition of the xanthine oxidase. J. Mol. Struct., 2014, 684(1-3), 1-7.
[44]
Lin, C.M.; Chen, C.T.; Lee, H.H.; Lin, J.K. Prevention of cellular ROS damage by isovitexin and related flavonoids. Planta Med., 2002, 68(4), 365-367.
[http://dx.doi.org/10.1055/s-2002-26753] [PMID: 11988866]
[45]
Ribeiro, D.; Freitas, M.; Tomé, S.M.; Silva, A.M.; Porto, G.; Cabrita, E.J.; Marques, M.M.; Fernandes, E. Inhibition of LOX by flavonoids: a structure-activity relationship study. Eur. J. Med. Chem., 2014, 72, 137-145.
[http://dx.doi.org/10.1016/j.ejmech.2013.11.030] [PMID: 24368208]
[46]
Huo, L.N.; Wang, W.; Zhang, C.Y.; Shi, H.B.; Liu, Y.; Liu, X.H.; Guo, B.H.; Zhao, D.M.; Gao, H. Bioassay-guided isolation and identification of xanthine oxidase inhibitory constituents from the leaves of Perilla frutescens. Molecules, 2015, 20(10), 17848-17859.
[http://dx.doi.org/10.3390/molecules201017848] [PMID: 26425999]
[47]
Wu, N.; Kong, Y.; Fu, Y.; Zu, Y.; Yang, Z.; Yang, M.; Peng, X.; Efferth, T. In vitro antioxidant properties, DNA damage protective activity, and xanthine oxidase inhibitory effect of cajaninstilbene acid, a stilbene compound derived from pigeon pea [Cajanus cajan (L.) Millsp.] leaves. J. Agric. Food Chem., 2011, 59(1), 437-443.
[http://dx.doi.org/10.1021/jf103970b] [PMID: 21128613]
[48]
Liu, Y.L.; Pan, Y.; Wang, X.; Fan, C.Y.; Zhu, Q.; Li, J.M.; Wang, S.J.; Kong, L.D. Betaine reduces serum uric acid levels and improves kidney function in hyperuricemic mice. Planta Med., 2014, 80(1), 39-47.
[PMID: 24338552]
[49]
Wang, G.F.; Shang, Y.J.; Jiao, B.H.; Huang, C.G. Renierol from marine sponge Haliclona.SP.: a natural inhibitor of xanthine oxidase with hypouricemic effects. J. Enzyme Inhib. Med. Chem., 2008, 23(3), 406-410.
[http://dx.doi.org/10.1080/14756360701612082] [PMID: 18569347]
[50]
Wang, R.D.; Su, G.H.; Wang, L.; Xia, Q.; Liu, R.; Lu, Q.; Zhang, J.L. Identification and mechanism of effective components from rape (Brassica napus L.) bee pollen on serum uric acid level and xanthine oxidase activity. J. Funct. Foods, 2018, 47, 241-251.
[http://dx.doi.org/10.1016/j.jff.2018.05.064]
[51]
Jhang, J.J.; Ong, J.W.; Lu, C.C.; Hsu, C.L.; Lin, J.H.; Liao, J.W.; Yen, G.C. Hypouricemic effects of Mesona procumbens Hemsl. through modulating xanthine oxidase activity in vitro and in vivo. Food Funct., 2016, 7(10), 4239-4246.
[http://dx.doi.org/10.1039/C6FO00822D] [PMID: 27713960]
[52]
Gawlik-Dziki, U.; Dziki, D.; Świeca, M.; Nowak, R. Mechanism of action and interactions between xanthine oxidase inhibitors derived from natural sources of chlorogenic and ferulic acids. Food Chem., 2017, 225, 138-145.
[http://dx.doi.org/10.1016/j.foodchem.2017.01.016] [PMID: 28193407]
[53]
Honda, S.; Fukuyama, Y.; Nishiwaki, H.; Masuda, A.; Masuda, T. Conversion to purpurogallin, a key step in the mechanism of the potent xanthine oxidase inhibitory activity of pyrogallol. Free Radic. Biol. Med., 2017, 106, 228-235.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.02.037] [PMID: 28223196]
[54]
Rasouli, H.; Hosseini-Ghazvini, S.M.B.; Adibi, H.; Khodarahmi, R. Differential α-amylase/α-glucosidase inhibitory activities of plant-derived phenolic compounds: a virtual screening perspective for the treatment of obesity and diabetes. Food Funct., 2017, 8(5), 1942-1954.
[http://dx.doi.org/10.1039/C7FO00220C] [PMID: 28470323]
[55]
Cao, H.; Pauff, J.M.; Hille, R. X-ray crystal structure of a xanthine oxidase complex with the flavonoid inhibitor quercetin. J. Nat. Prod., 2014, 77(7), 1693-1699.
[http://dx.doi.org/10.1021/np500320g] [PMID: 25060641]
[56]
Nagao, A.; Seki, M.; Kobayashi, H. Inhibition of xanthine oxidase by flavonoids. Biosci. Biotechnol. Biochem., 1999, 63(10), 1787-1790.
[http://dx.doi.org/10.1271/bbb.63.1787] [PMID: 10671036]
[57]
Pauff, J.M.; Hille, R. Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J. Nat. Prod., 2009, 72(4), 725-731.
[http://dx.doi.org/10.1021/np8007123] [PMID: 19388706]
[58]
Zhang, Z.C.; Zhou, Q.; Yang, Y.; Wang, Y.; Zhang, J.L. Highly acylated anthocyanins from purple sweet potato (Ipomoea batatas L.) alleviate hyperuricemia and kidney inflammation in hyperuricemic mice: possible attenuation effects on allopurinol. J. Agric. Food Chem., 2019, 67(22), 6202-6211.
[http://dx.doi.org/10.1021/acs.jafc.9b01810] [PMID: 31091873]
[59]
Peng, A.; Lin, L.; Zhao, M.; Sun, B. Identifying mechanisms underlying amelioration effect of Chrysanthemum morifolium Ramat.‘Boju’extract on hyperuricemia using biochemical characterization and UPLC-ESI-QTOF/MS-based metabolomics. Food Funct., 2019.
[http://dx.doi.org/10.1039/C9FO01821B]
[60]
Chen, L.; Li, M.; Wu, J.L.; Li, J.X.; Ma, Z.C. Effect of lemon water soluble extract on hyperuricemia in a mouse model. Food Funct., 2019, 10(9), 6000-6008.
[http://dx.doi.org/10.1039/C9FO00509A] [PMID: 31482168]
[61]
Liu, C.; Zhou, H.N.; Zhang, R.R.; Wang, X.K.; He, S.W.; Zhang, J.B.; Sun, J.Y. Anti-hyperuricemic and nephroprotective effect of geniposide in chronic hyperuricemia mice. J. Funct. Foods, 2019, 61, 103355.
[http://dx.doi.org/10.1016/j.jff.2019.05.011]
[62]
Wan, Y.; Wang, F.; Zou, B.; Shen, Y.; Li, Y.; Zhang, A.; Fu, G. Molecular mechanism underlying the ability of caffeic acid to decrease uric acid levels in hyperuricemia rats. J. Funct. Foods, 2019, 57, 150-156.
[http://dx.doi.org/10.1016/j.jff.2019.03.038]

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