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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Natural Products and Extracts as Xantine Oxidase Inhibitors - A Hope for Gout Disease?

Author(s): Ilkay E. Orhan* and Fatma S.S. Deniz

Volume 27, Issue 2, 2021

Published on: 28 July, 2020

Page: [143 - 158] Pages: 16

DOI: 10.2174/1381612826666200728144605


Xanthine oxidase (EC (XO) is one of the main enzymatic sources that create reactive oxygen species (ROS) in the living system. It is a dehydrogenase enzyme that performs electron transfer to nicotinamide adenine dinucleotide (NAD+), while oxidizing hypoxanthin, which is an intermediate compound in purine catabolism, first to xanthine and then to uric acid. XO turns into an oxidant enzyme that oxidizes thiol groups under certain stress conditions in the tissue. The last metabolic step, in which hypoxanthin turns into uric acid, is catalyzed by XO. Uric acid, considered a waste product, can cause kidney stones and gouty-type arthritis as it is crystallized, when present in high concentrations. Thus, XO inhibitors are one of the drug classes used against gout, a purine metabolism disease that causes urate crystal storage in the joint and its surroundings caused by hyperuricemia. Urate-lowering therapy includes XO inhibitors that reduce uric acid production as well as uricosuric drugs that increase urea excretion. Current drugs that obstruct uric acid synthesis through XO inhibition are allopurinol, febuxostat, and uricase. However, since the side effects, safety and tolerability problems of some current gout medications still exist, intensive research is ongoing to look for new, effective, and safer XO inhibitors of natural or synthetic origins for the treatment of the disease. In the present review, we aimed to assess in detail XO inhibitory capacities of pure natural compounds along with the extracts from plants and other natural sources via screening Pubmed, Web of Science (WoS), Scopus, and Google Academic. The data pointed out to the fact that natural products, particularly phenolics such as flavonoids (quercetin, apigenin, and scutellarein), tannins (agrimoniin and ellagitannin), chalcones (melanoxethin), triterpenes (ginsenoside Rd and ursolic acid), stilbenes (resveratrol and piceatannol), alkaloids (berberin and palmatin) have a great potential for new XO inhibitors capable of use against gout disease. In addition, not only plants but other biological sources such as microfungi, macrofungi, lichens, insects (silk worms, ants, etc) seem to be the promising sources of novel XO inhibitors.

Keywords: Xanthine oxidase, inhibition, gout, plant, natural sources, agrimoniin and ellagitannin.

Hainer BL, Matheson E, Wilkes RT. Diagnosis, treatment, and prevention of gout. Am Fam Physician 2014; 90(12): 831-6.
[PMID: 25591183]
Dalbeth N, Merriman TR, Stamp LK. Gout Lancet 2016; 388(10055): 2039-52. []. [PMID: 27112094].
Ruoff G, Edwards NL. Overview of serum uric acid treatment targets in gout: Why less than 6 mg/dL? Postgrad Med 2016; 128(7): 706-15. []. [PMID: 27558643].
Atakul N, Demir H. Gut tedavisinde kullanılan ilaçlar Türkiye Klinikleri - Special Topics 2014; 7(4): 42-7.
Guttmann A, Krasnokutsky S, Pillinger MH, Berhanu A. Pegloticase in gout treatment - safety issues, latest evidence and clinical considerations. Ther Adv Drug Saf 2017; 8(12): 379-88. []. [PMID: 29204266].
Bayraktar A. Hiperürisemi ve gut. TEB Haberler 2010; 2: 22-5.
Kanbay M, Huddam B, Azak A, et al. A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol 2011; 6(8): 1887-94. []. [PMID: 21784838].
Cicero AFG, Pirro M, Watts GF, Mikhailidis DP, Banach M, Sahebkar A. Effects of allopurinol on endothelial function: a systematic review and meta-analysis of randomized placebo-controlled trials. Drugs 2018; 78(1): 99-109. []. [PMID: 29139092].
Conaghan PG, Day RO. Risks and benefits of drugs used in the management and prevention of gout. Drug Saf 1994; 11(4): 252-8. []. [PMID: 7848545].
Strilchuk L, Fogacci F, Cicero AF. Safety and tolerability of available urate-lowering drugs: a critical review. Expert Opin Drug Saf 2019; 18(4): 261-71. []. [PMID: 30915866].
Koca F, Karadeniz F. Serbest radikal oluşum mekanizmaları ve vücuttaki antioksidan savunma sistemleri. Gıda Mühendisliği Dergisi 2014; pp. 32-7.
Kostic DA, Dimitrijevic DS, Stojanovic GS, Palic IR, Yorzevic AS, Ickovski JD. Xanthine oxidase: isolation, assays of activity, and inhibition. J Chem 2015; 2015294858 [].
Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39(1): 44-84. []. [PMID: 16978905].
Sen S, Chakraborty R, Sridhar C, Reddy YSR, De B. Free radicals, antioxidants, diseases and phytomedicines: current status and future prospect. Int J Pharm Sci Res 2010; 3(1): 91-100.
Schardinger F. Ueber das verhalten der kuhmilchgegen methylenblau und seine verwendungzur unterscheidung von ungekochterund gekochtermilch 1902; 5(22): 1113-21.
Morgan EJ, Stewart CP, Hopkins FG. On the anaerobic and aerobic oxidation of xanthine and hypoxanthin by tissues and by milk. Proc R Soc Lond, B 1922; 94(657): 109-31. [].
Booth VH. The specificity of xanthine oxidase. Biochem J 1938; 32(3): 494-502. []. [PMID: 16746646].
Ojha R, Singh J, Ojha A, Singh H, Sharma S, Nepali K. An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015). Expert Opin Ther Pat 2017; 27(3): 311-45. []. [PMID: 27841045].
Hatano T, Yasuhara T, Fukuda T, Noro T, Okuda T. Phenolic constituents of licorice. II. Structures of licopyranocoumarin, licoarylcoumarin and glisoflavone, and inhibitory effects of licorice phenolics on xanthine oxidase. Chem Pharm Bull (Tokyo) 1989; 37(11): 3005-9. []. [PMID: 2632045].
Yang TH, Yan DX, Huang XY, et al. Termipaniculatones A-F, chalcone-flavonone heterodimers from Terminthia paniculata, and their protective effects on hyperuricemia and acute gouty arthritis. Phytochemistry 2019; 164: 228-35. []. [PMID: 31181354].
Ding Z, Dai Y, Wang Z. Hypouricemic action of scopoletin arising from xanthine oxidase inhibition and uricosuric activity. Planta Med 2005; 71(2): 183-5. []. [PMID: 15729630].
Dew TP, Day AJ, Morgan MR. Xanthine oxidase activity in vitro: effects of food extracts and components. J Agric Food Chem 2005; 53(16): 6510-5. []. [PMID: 16076142].
Nguyen MT, Awale S, Tezuka Y, Tran QL, Kadota S. Xanthine oxidase inhibitors from the heartwood of Vietnamese Caesalpinia sappan. Chem Pharm Bull (Tokyo) 2005; 53(8): 984-8. []. [PMID: 16079532].
Trevisan MT, Pfundstein B, Haubner R, et al. Characterization of alkyl phenols in cashew (Anacardium occidentale) products and assay of their antioxidant capacity. Food Chem Toxicol 2006; 44(2): 188-97. []. [PMID: 16095792].
Phuwapraisirisan P, Sowanthip P, Miles DH, Tip-pyang S. Reactive radical scavenging and xanthine oxidase inhibition of proanthocyanidins from Carallia brachiata. Phytother Res 2006; 20(6): 458-61. []. [PMID: 16619354].
Nguyen MT, Awale S, Tezuka Y, Ueda JY. Tran Ql, Kadota S. Xanthine oxidase inhibitors from the flowers of Chrysanthemum sinense. Planta Med 2006; 72(1): 46-51. []. [PMID: 16450295].
Jiao RH, Ge HM, Shi H, Tan RX. An apigenin-derived xanthine oxidase inhibitor from Palhinhaea cernua. J Nat Prod 2006; 69(7): 1089-91. []. [PMID: 16872152].
Hsieh JF, Wu SH, Yang YL, Choong KF, Chen ST. The screening and characterization of 6-aminopurine-based xanthine oxidase inhibitors. Bioorg Med Chem 2007; 15(10): 3450-6. []. [PMID: 17379526].
Wu CC, Yen MH, Yang SC, Lin CN. Phloroglucinols with antioxidant activity and xanthonolignoids from the heartwood of Hypericum geminiflorum. J Nat Prod 2008; 71(6): 1027-31. []. [PMID: 18512985].
Ngoc TM, Hung TM, Thuong PT, et al. Antioxidative activities of galloyl glucopyranosides from the stem-bark of Juglans mandshurica. Biosci Biotechnol Biochem 2008; 72(8): 2158-63. []. [PMID: 18685223].
Ko HH, Chang WL, Lu TM. Antityrosinase and antioxidant effects of ent-kaurane diterpenes from leaves of Broussonetia papyrifera. J Nat Prod 2008; 71(11): 1930-3. []. [PMID: 18986201].
Chien SC, Yang CW, Tseng YH, Tsay HS, Kuo YH, Wang SY. Lonicera hypoglauca inhibits xanthine oxidase and reduces serum uric acid in mice. Planta Med 2009; 75(4): 302-6. []. [PMID: 19184967].
Murata K, Nakao K, Hirata N, et al. Hydroxychavicol: a potent xanthine oxidase inhibitor obtained from the leaves of betel, Piper betle. J Nat Med 2009; 63(3): 355-9. []. [PMID: 19387769].
He ZZ, Yan JF, Song ZJ, et al. Chemical constituents from the aerial parts of Artemisia minor. J Nat Prod 2009; 72(6): 1198-201. []. [PMID: 19476336].
Tsai SF, Lee SS. Neolignans as xanthine oxidase inhibitors from Hyptis rhomboides. Phytochemistry 2014; 101: 121-7. []. [PMID: 24559911].
Zhu LL, Fu WW, Watanabe S, et al. Xanthine oxidase inhibitors from Garcinia esculenta twigs. Planta Med 2014; 80(18): 1721-6. []. [PMID: 25340468].
Maffei Facino R, Carini M, Aldini G, Bombardelli E, Morazzoni P, Morelli R. Free radicals scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action. Arzneimittelforschung 1994; 44(5): 592-601.
[PMID: 8024628]
Zhang X, Hung TM, Phuong PT, et al. Anti-inflammatory activity of flavonoids from Populus davidiana. Arch Pharm Res 2006; 29(12): 1102-8. []. [PMID: 17225458].
Gyamfi MA, Aniya Y. Antioxidant properties of Thonningianin A, isolated from the African medicinal herb, Thonningia sanguinea. Biochem Pharmacol 2002; 63(9): 1725-37. []. [PMID: 12007576].
Noro T, Sekiya T, Katoh M, et al. Inhibitors of xanthine oxidase from Alpinia galanga. Chem Pharm Bull (Tokyo) 1988; 36: 244-8. [].
Ho KY, Huang JS, Tsai CC, Lin TC, Hsu YF, Lin CC. Antioxidant activity of tannin components from Vaccinium vitis-idaea L. J Pharm Pharmacol 1999; 51(9): 1075-8. []. [PMID: 10528992].
Huang CG, Shang YJ, Zhang J, Zhang JR, Li WJ, Jiao BH. Hypouricemic effects of phenylpropanoid glycosides acteoside of Scrophularia ningpoensis on serum uric acid levels in potassium oxonate-pretreated Mice. Am J Chin Med 2008; 36(1): 149-57. []. [PMID: 18306458].
Xiong Q, Kadota S, Tani T, Namba T. Antioxidative effects of phenylethanoids from Cistanche deserticola. Biol Pharm Bull 1996; 19(12): 1580-5. []. [PMID: 8996643].
Jagadeeshwar Rao R, Tiwari AK, Kumar US, Reddy SV, Ali AZ, Rao JM. Novel 3-O-acyl mesquitol analogues as free-radical scavengers and enzyme inhibitors: synthesis, biological evaluation and structure-activity relationship. Bioorg Med Chem Lett 2003; 13(16): 2777-80. []. [PMID: 12873513].
Sarawek S, Feistel B, Pischel I, Butterweck V. Flavonoids of Cynara scolymus possess potent xanthinoxidase inhibitory activity in vitro but are devoid of hypouricemic effects in rats after oral application. Planta Med 2008; 74(3): 221-7. []. [PMID: 18300193].
An BJ, Kwak JH, Park JM, et al. Inhibition of enzyme activities and the antiwrinkle effect of polyphenol isolated from the persimmon leaf (Diospyros kaki folium) on human skin. Dermatol Surg 2005; 31(7 Pt. 2): 848-54. []. [PMID: 16029677].
Leu SJ, Lin YP, Lin RD, et al. Phenolic constituents of Malus doumeri var. formosana in the field of skin care. Biol Pharm Bull 2006; 29(4): 740-5. []. [PMID: 16595910].
de la Puerta R, Forder RA, Hoult JR. Inhibition of leukocyte eicosanoid generation and radical scavenging activity by gnaphalin, a lipophilic flavonol isolated from Helichrysum picardii. Planta Med 1999; 65(6): 507-11. []. [PMID: 10483368].
Liu X, Chen R, Shang Y, Jiao B, Huang C. Superoxide radicals scavenging and xanthine oxidase inhibitory activity of magnesium lithospermate B from Salvia miltiorrhiza. J Enzyme Inhib Med Chem 2009; 24(3): 663-8. []. [PMID: 18686136].
Falodun A, Qadir MI, Chouldary MI. Isolation and characterization of xanthine oxidase inhibitory constituents of Pyrenacantha staudtii. Yao Xue Xue Bao 2009; 44(4): 390-4.
[PMID: 19545057]
Atta-ur- Rahman, Naz H, Fadimatou , et al. Bioactive constituents from Boswellia papyrifera. J Nat Prod 2005; 68(2): 189-93. []. [PMID: 15730241].
Ali MS, Ibrahim SA, Jalil S, Choudhary MI. Ursolic acid: a potent inhibitor of superoxides produced in the cellular system. Phytother Res 2007; 21(6): 558-61. []. [PMID: 17295383].
Gariboldi E, Mascetti D, Galli G, Caballion P, Bosisio E. LC-UV-electrospray-MS-MS mass spectrometry analysis of plant constituents inhibiting xanthine oxidase. Pharm Res 1998; 15(6): 936-43. []. [PMID: 9647362].
Chander R, Kapoor NK, Dhawan BN. Picroliv, picroside-I and kutkoside from Picrorhiza kurrooa are scavengers of superoxide anions. Biochem Pharmacol 1992; 44(1): 180-3. []. [PMID: 1321626].
Kweon MH, Hwang HJ, Sung HC. Identification and antioxidant activity of novel chlorogenic acid derivatives from bamboo (Phyllostachys edulis). J Agric Food Chem 2001; 49(10): 4646-55. []. [PMID: 11600002].
Fogliani B, Raharivelomanana P, Bianchini JP, Bouraïma-Madjèbi S, Hnawia E. Bioactive ellagitannins from Cunonia macrophylla, an endemic Cunoniaceae from New Caledonia. Phytochemistry 2005; 66(2): 241-7. []. [PMID: 15652581].
Andriani Y, Syamsumir DF, Yee TC, et al. Biological activities of isolated compounds from three edible Malaysian red seaweeds, Gracilaria changii, G. manilaensis and Gracilaria sp. Nat Prod Commun 2016; 11(8): 1117-20. []. [PMID: 30725572].
Bazylko A, Piwowarski JP, Filipek A, Bonarewicz J, Tomczyk M. In vitro antioxidant and anti-inflammatory activities of extracts from Potentilla recta and its main ellagitannin, agrimoniin. J Ethnopharmacol 2013; 149(1): 222-7. []. [PMID: 23811215].
Bouhlel I, Limem I, Skandrani I, et al. Assessment of isorhamnetin 3-O-neohesperidoside from Acacia salicina: protective effects toward oxidation damage and genotoxicity induced by aflatoxin B1 and nifuroxazide. J Appl Toxicol 2010; 30(6): 551-8. []. [PMID: 20809543].
Lin KW, Huang AM, Tu HY, et al. Phloroglucinols inhibit chemical mediators and xanthine oxidase, and protect cisplatin-induced cell death by reducing reactive oxygen species in normal human urothelial and bladder cancer cells. J Agric Food Chem 2009; 57(19): 8782-7. []. [PMID: 19754119].
Karim A, Noor AT, Malik A, Qadir MI, Choudhary MI. Barlerisides A and B, new potent superoxide scavenging phenolic glycosides from Barleria acanthoides. J Enzyme Inhib Med Chem 2009; 24(6): 1332-5. []. [PMID: 19912065].
Kumar US, Tiwari AK, Reddy SV, et al. Free-radical-scavenging and xanthine oxidase inhibitory constituents from Stereospermum personatum. J Nat Prod 2005; 68(11): 1615-21. []. [PMID: 16309309].
Wang SY, Yang CW, Liao JW, Zhen WW, Chu FH, Chang ST. Essential oil from leaves of Cinnamomum osmophloeum acts as a xanthine oxidase inhibitor and reduces the serum uric acid levels in oxonate-induced mice. Phytomedicine 2008; 15(11): 940-5. []. [PMID: 18693097].
Chang WS, Lee YJ, Lu FJ, Chiang HC. Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Res 1993; 13(6A): 2165-70.
[PMID: 8297130]
Valentão P, Fernandes E, Carvalho F, Andrade PB, Seabra RM, Bastos ML. Antioxidant activity of Centaurium erythraea infusion evidenced by its superoxide radical scavenging and xanthine oxidase inhibitory activity. J Agric Food Chem 2001; 49(7): 3476-9. []. [PMID: 11453794].
Tung YT, Chang ST. Inhibition of xanthine oxidase by Acacia confusa extracts and their phytochemicals. J Agric Food Chem 2010; 58(2): 781-6. []. [PMID: 20047272].
Chang WS, Chang YH, Lu FJ, Chiang HC. Inhibitory effects of phenolics on xanthine oxidase. Anticancer Res 1994; 14(2A): 501-6.
[PMID: 8017853]
Wang J, Shi D, Zheng M, et al. Screening, separation, and evaluation of xanthine oxidase inhibitors from Paeonia lactiflora using chromatography combined with a multi-mode microplate reader. J Sep Sci 2017; 40(21): 4160-7. []. [PMID: 28857450].
Niu Y, Liu J, Liu HY, et al. Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity. Pharm Biol 2016; 54(9): 1680-6. []. [PMID: 26916555].
Nguyen MT, Nguyen NT. Xanthine oxidase inhibitors from Vietnamese Blumea balsamifera L. Phytother Res 2012; 26(8): 1178-81. []. [PMID: 22821854].
Li S, Tang Y, Liu C, Li J, Guo L, Zhang Y. Development of a method to screen and isolate potential xanthine oxidase inhibitors from Panax japlcus var via ultrafiltration liquid chromatography combined with counter-current chromatography. Talanta 2015; 134: 665-73. []. [PMID: 25618720].
Tang X, Tang P, Ma L, Liu L. Screening and evaluation of xanthine oxidase inhibitors from Gnetum parvifolium in China. Molecules 2019; 24(14)E2671 []. [PMID: 31340570].
Kong LD, Abliz Z, Zhou CX, Li LJ, Cheng CH, Tan RX. Glycosides and xanthine oxidase inhibitors from Conyza bonariensis. Phytochemistry 2001; 58(4): 645-51. []. [PMID: 11576616].
Kong LD, Wolfender JL, Cheng CH, Hostettmann K, Tan RX. Xanthine oxidase inhibitors from Brandisia hancei. Planta Med 1999; 65(8): 744-6. []. [PMID: 10630118].
Nile SH, Park SW. Antioxidant, α-glucosidase and xanthine oxidase inhibitory activity of bioactive compounds from maize (Zea mays L.). Chem Biol Drug Des 2014; 83(1): 119-25. []. [PMID: 23957301].
Kondo M, Hirano Y, Nishio M, Furuya Y, Nakamura H, Watanabe T. Xanthine oxidase inhibitory activity and hypouricemic effect of aspalathin from unfermented rooibos. J Food Sci 2013; 78(12): H1935-9. []. [PMID: 24261664].
Xu F, Zhao X, Yang L, Wang X, Zhao J. A new cycloartane-type triterpenoid saponin xanthine oxidase inhibitor from Homonoia riparia Lour. Molecules 2014; 19(9): 13422-31. []. [PMID: 25178063].
Liu XX, Sun SW, Yuan WJ, et al. Isolation of tricin as a xanthine oxidase inhibitor from sweet white clover (Melilotus albus) and its distribution in selected Gramineae species. Molecules 2018; 23(10)E2719 []. [PMID: 30360380].
Abu-Gharbieh E, Shehab NG, Almasri IM, Bustanji Y. Antihyperuricemic and xanthine oxidase inhibitory activities of Tribulus arabicus and its isolated compound, ursolic acid: In vitro and in vivo investigation and docking simulations. PLoS One 2018; 13(8)e0202572 []. [PMID: 30114281].
Huo LN, Wang W, Zhang CY, et al. Bioassay-guided isolation and identification of xanthine oxidase inhibitory constituents from the leaves of Perilla frutescens. Molecules 2015; 20(10): 17848-59. []. [PMID: 26425999].
Song HP, Zhang H, Fu Y, et al. Screening for selective inhibitors of xanthine oxidase from Flos Chrysanthemum using ultrafiltration LC-MS combined with enzyme channel blocking. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 961: 56-61. []. [PMID: 24861872].
Unno T, Sugimoto A, Kakuda T. Xanthine oxidase inhibitors from the leaves of Lagerstroemia speciosa (L.). Pers J Ethnopharmacol 2004; 93(2-3): 391-5. []. [PMID: 15234783].
Li S, Liu C, Guo L, et al. Ultrafiltration liquid chromatography combined with high-speed countercurrent chromatography for screening and isolating potential α-glucosidase and xanthine oxidase inhibitors from Cortex Phellodendri. J Sep Sci 2014; 37(18): 2504-12. []. [PMID: 24975280].
Yuk HJ, Lee YS, Ryu HW, Kim SH, Kim DS. Effects of Toona sinensis leaf extract and its chemical constituents on xanthine oxidase activity and serum uric acid levels in potassium oxonate-ınduced hyperuricemic rats. Molecules 2018; 23(12)E3254 []. [PMID: 30544886].
Ranjana NZ, Nooreen Z, Bushra U, et al. Standardization and xanthine oxidase inhibitory potential of Zanthoxylum armatum fruits. J Ethnopharmacol 2019; 230: 1-8. []. [PMID: 30342965].
Insanu M, Ramadhania ZM, Halim EN, Hartati R, Wirasutisna KR. Isolation of 5,7-dihydroxy, 6,8-dimethyl flavanone from Syzygium aqueum with its antioxidant and xanthine oxidase inhibitor activities. Pharmacognosy Res 2018; 10(1): 60-3.
[PMID: 29568189]
Kim DW, Curtis-Long MJ, Yuk HJ, et al. Quantitative analysis of phenolic metabolites from different parts of Angelica keiskei by HPLC-ESI MS/MS and their xanthine oxidase inhibition. Food Chem 2014; 153: 20-7. []. [PMID: 24491695].
Chu YH, Chen CJ, Wu SH, Hsieh JF. Inhibition of xanthine oxidase by Rhodiola crenulata extracts and their phytochemicals. J Agric Food Chem 2014; 62(17): 3742-9. []. [PMID: 24712453].
Liu K, Wang W, Guo BH, et al. Chemical evidence for potent xanthine oxidase inhibitory activity of ethyl acetate extract of Citrus aurantium L. dried immature fruits. Molecules 2016; 21(3): 302. []. [PMID: 26950105].
Raziq N, Saeed M, Ali MS, Zafar S, Shahid M, Lateef M. A new glycosidic antioxidant from Ranunculus muricatus L. (Ranunculaceae) exhibited lipoxygenasae and xanthine oxidase inhibition properties. Nat Prod Res 2017; 31(11): 1251-7. []. [PMID: 27670108].
Kim JK, Kim WJ, Hyun JM, et al. Salvia plebeia extract inhibits xanthine oxidase activity in vitro and reduces serum uric acid in an animal model of hyperuricemia. Planta Med 2017; 83(17): 1335-41. []. [PMID: 28521370].
Baki Kekilli E. Pharmacognostic researches on establishing new xanthine oxidase inhibitors of herbal origin Ph.D. Thesis (supervisor:Orhan, I.E.), Institute of Health Sciences, Gazi University, Ankara,Turkey,2019
Meneshian A, Bulkley GB. The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction. Microcirculation 2002; 9(3): 161-75. []. [PMID: 12080414].
Dawson J, Walters M. Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease? Br J Clin Pharmacol 2006; 62(6): 633-44. []. [PMID: 21894646].
Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 2006; 58(1): 87-114. []. [PMID: 16507884].
Santi MD, Paulino Zunini M, Vera B, et al. Xanthine oxidase inhibitory activity of natural and hemisynthetic flavonoids from Gardenia oudiepe (Rubiaceae) in vitro and molecular docking studies. Eur J Med Chem 2018; 143: 577-82. []. [PMID: 29207340].
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): 7784-94. []. [PMID: 26285120].
Zhou LY, Peng JL, Wang JM, Geng YY, Zuo ZL, Hua Y. Structure-activity relationship of xanthones as inhibitors of xanthine oxidase. Molecules 2018; 23(2): 365. []. [PMID: 29425137].
Zhou CX, Kong LD, Ye WC, Cheng CH, Tan RX. Inhibition of xanthine and monoamine oxidases by stilbenoids from Veratrum taliense. Planta Med 2001; 67(2): 158-61. []. [PMID: 11301865].
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: 108-18. []. [PMID: 29502809].
Nishiwaki K, Ohigashi K, Deguchi T, et al. Structure-activity relationships and docking studies of hydroxychavicol and its analogs as xanthine oxidase inhibitors. Chem Pharm Bull (Tokyo) 2018; 66(7): 741-7. []. [PMID: 29695658].
Muzychka OV, Kobzar OL, Popova AV, Frasinyuk MS, Vovk AI. Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase. Bioorg Med Chem 2017; 25(14): 3606-13. []. [PMID: 28545814].
Tang HJ, Li W, Zhou M, et al. Design, synthesis and biological evaluation of novel xanthine oxidase inhibitors bearing a 2-arylbenzo[b]furan scaffold. Eur J Med Chem 2018; 151: 849-60. []. [PMID: 29684895].
Cao H, Pauff JM, Hille R. X-ray crystal structure of a xanthine oxidase complex with the flavonoid inhibitor quercetin. J Nat Prod 2014; 77(7): 1693-9. []. [PMID: 25060641].
Sakurai T, Sugawara H, Saito K, Kano Y. Effects of the acetylene compound from Atractylodes rhizome on experimental gastric ulcers induced by active oxygen species. Biol Pharm Bull 1994; 17(10): 1364-8. []. [PMID: 7874060].
Bangou MJ, Kiendrebeogo M, Meda NT, et al. Evaluation of enzymes inhibition activities of medicinal plant from Burkina Faso. Pak J Biol Sci 2011; 14(2): 99-105. []. [PMID: 21916259].
Salvamani S, Gunasekaran B, Shukor MY, Shaharuddin NA, Sabullah MK, Ahmad SA. Anti-HMG-CoA reductase, antioxidant, and anti-inflammatory activities of Amaranthus viridis leaf extract as a potential treatment for hypercholesterolemia. Evid Based Complement Alternat Med 2016; 20168090841 []. [PMID: 27051453].
Lavelli V. Comparison of the antioxidant activities of extra virgin olive oils. J Agric Food Chem 2002; 50(26): 7704-8. []. [PMID: 12475292].
Rani MP, Padmakumari KP. In vitro studies to assess the antidiabetic, antiperoxidative, and radical scavenging potential of Stereospermum colais. Pharm Biol 2012; 50(10): 1254-60. []. [PMID: 22900639].
Muñoz O, Christen P, Cretton S, et al. Chemical study and anti-inflammatory, analgesic and antioxidant activities of the leaves of Aristotelia chilensis (Mol.) Stuntz, Elaeocarpaceae. J Pharm Pharmacol 2011; 63(6): 849-59. []. [PMID: 21585384].
Behera BC, Adawadkar B, Makhija U. Tissue-culture of selected species of the Graphis lichen and their biological activities. Fitoterapia 2006; 77(3): 208-15. []. [PMID: 16530344].
Prathapan A, Lijo Cherian O, Nampoothiri SV, Mini S, Raghu KG. In vitro antiperoxidative, free radical scavenging and xanthine oxidase inhibitory potentials of ethyl acetate fraction of Saraca ashoka flowers. Nat Prod Res 2011; 25(3): 298-309. []. [PMID: 21294042].
Meda NT, Lamien-Meda A, Kiendrebeogo M, et al. In vitro antioxidant, xanthine oxidase and acetylcholinesterase inhibitory activities of Balanites aegyptiaca (L.) Del. (Balanitaceae). Pak J Biol Sci 2010; 13(8): 362-8. []. [PMID: 20836295].
Chen K, Ye C, Plumb GW, Bao Y. [Investigation on the antioxidant activities in vitro of extracts from Ampelopsis humilifolia var. heterophylla and A. sinica].. Zhong Yao Cai 2004; 27(9): 650-3.
[PMID: 15704583]
Palu A, Deng S, West B, Jensen J. Xanthine oxidase inhibiting effects of noni (Morinda citrifolia) fruit juice. Phytother Res 2009; 23(12): 1790-1. []. [PMID: 19434757].
Filha ZS, Vitolo IF, Fietto LG, Lombardi JA, Saúde-Guimarães DA. Xanthine oxidase inhibitory activity of Lychnophora species from Brazil (“Arnica”). J Ethnopharmacol 2006; 107(1): 79-82. []. [PMID: 16621372].
Umamaheswari M. AsokKumar K, Somasundaram A, Sivashanmugam T, Subhadradevi V, Ravi TK. Xanthine oxidase inhibitory activity of some Indian medical plants. J Ethnopharmacol 2007; 109(3): 547-51. []. [PMID: 17014977].
Boumerfeg S, Baghiani A, Messaoudi D, Khennouf S, Arrar L. Antioxidant properties and xanthine oxidase inhibitory effects of Tamus communis L. root extracts. Phytother Res 2009; 23(2): 283-8. []. [PMID: 18844260].
Murugaiyah V, Chan KL. Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents. J Ethnopharmacol 2009; 124(2): 233-9. []. [PMID: 19397979].
Umamaheswari M, Asokkumar K, Sivashanmugam AT, Remyaraju A, Subhadradevi V, Ravi TK. In vitro xanthine oxidase inhibitory activity of the fractions of Erythrina stricta Roxb. J Ethnopharmacol 2009; 124(3): 646-8. []. [PMID: 19467311].
Lopes Galeno DM, Carvalho RP, Boleti AP, et al. Extract from Eugenia punicifolia is an antioxidant and inhibits enzymes related to metabolic syndrome. Appl Biochem Biotechnol 2014; 172(1): 311-24. []. [PMID: 24078187].
Fais A, Era B, Di Petrillo A, et al. Selected enzyme inhibitory effects of Euphorbia characias extracts. BioMed Res Int 2018; 20181219367 []. [PMID: 30003087].
Ben Bacha A, Jemel I, Bhat RS, Onizi MA. Inhibitory effects of various solvent extracts from Rhamnus frangula leaves on some inflammatory and metabolic enzymes. Cell Mol Biol 2018; 64(13): 55-62. []. [PMID: 30403596].
Owen PL, Johns T. Xanthine oxidase inhibitory activity of northeastern North American plant remedies used for gout. J Ethnopharmacol 1999; 64(2): 149-60. []. [PMID: 10197750].
Duong NT, Vinh PD, Thuong PT, et al. Xanthine oxidase inhibitors from Archidendron clypearia (Jack.) I.C. Nielsen: Results from systematic screening of Vietnamese medicinal plants. Asian Pac J Trop Med 2017; 10(6): 549-56. []. [PMID: 28756918].
Orbán-Gyapai O, Lajter I, Hohmann J, Jakab G, Vasas A. Xanthine oxidase inhibitory activity of extracts prepared from Polygonaceae species. Phytother Res 2015; 29(3): 459-65. []. [PMID: 25510560].
Di Petrillo A, María González-Paramás A, Rosa A, et al. Chemical composition and enzyme inhibition of Phytolacca dioica L. seeds extracts. J Enzyme Inhib Med Chem 2019; 34(1): 519-27. []. [PMID: 30688117].
Kırmızıbekmez H, Tiftik K, Kúsz N, Orban-Gyapai O, Zomborszki ZP, Hohmann J. Three new iridoid glycosides from the aerial parts of Asperula involucrata. Chem Biodivers 2017; 14(3) []. [PMID: 27935658].
Song SY, Song SH, Bae MS, Cho SS. Phytochemical constituents and the evaluation biological effect of Cinnamomum yabunikkei H. Ohba leaf. Molecules 2018; 24(1)E81 []. [PMID: 30591631].
Pereira OR, Catarino MD, Afonso AF, Silva AMS, Cardoso SM. Salvia elegans, Salvia greggii and Salvia officinalis decoctions: antioxidant activities and inhibition of carbohydrate and lipid metabolic enzymes. Molecules 2018; 23(12)E3169 []. [PMID: 30513773].
Havlik J, Gonzalez de la Huebra R, Hejtmankova K, et al. Xanthine oxidase inhibitory properties of Czech medicinal plants. J Ethnopharmacol 2010; 132(2): 461-5. []. [PMID: 20800669].
Belhaddad OE, Charef N, Amamra S, et al. Chromatographic fractionation, antioxidant and antibacterial activities of Urginea maritima methanolic extract. Pak J Pharm Sci 2017; 30(1): 127-34.
[PMID: 28603122]
Sweeney AP, Wyllie SG, Shalliker RA, Markham JL. Xanthine oxidase inhibitory activity of selected Australian native plants. J Ethnopharmacol 2001; 75(2-3): 273-7. []. [PMID: 11297862].
Ammar RB, Sghaier MB, Boubaker J, et al. Antioxidant activity and inhibition of aflatoxin B1-, nifuroxazide-, and sodium azide-induced mutagenicity by extracts from Rhamnus alaternus L. Chem Biol Interact 2008; 174(1): 1-10. []. [PMID: 18511029].
Ammar RB, Kilani S, Bouhlel I, et al. Antiproliferative, antioxidant, and antimutagenic activities of flavonoid-enriched extracts from (Tunisian) Rhamnus alaternus L.: combination with the phytochemical composition. Drug Chem Toxicol 2008; 31(1): 61-80. []. [PMID: 18161508].
Yoo EA, Kim SD, Lee WM, et al. Evaluation of antioxidant, antinociceptive, and anti-inflammatory activities of ethanol extracts from Aloe saponaria Haw. Phytother Res 2008; 22(10): 1389-95. []. [PMID: 18688813].
Zhao X, Zhu JX, Mo SF, Pan Y, Kong LD. Effects of cassia oil on serum and hepatic uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. J Ethnopharmacol 2006; 103(3): 357-65. []. [PMID: 16182482].
Irondi EA, Agboola SO, Oboh G, Boligon AA, Athayde ML, Shode FO. Guava leaves polyphenolics-rich extract inhibits vital enzymes implicated in gout and hypertension in vitro. J Intercult Ethnopharmacol 2016; 5(2): 122-30. []. [PMID: 27104032].
Napagoda M, Gerstmeier J, Butschek H, et al. Lipophilic extracts of Leucas zeylanica, a multi-purpose medicinal plant in the tropics, inhibit key enzymes involved in inflammation and gout. J Ethnopharmacol 2018; 224: 474-81. []. [PMID: 29727733].
Mitomo S, Hirota M, Fujita T. New xanthine oxidase inhibitors from the fruiting bodies of Tyromyces fissilis. Biosci Biotechnol Biochem 2019; 83(5): 813-23. []. [PMID: 30730255].
Lin KW, Chen YT, Yang SC, Wei BL, Hung CF, Lin CN. Xanthine oxidase inhibitory lanostanoids from Ganoderma tsugae. Fitoterapia 2013; 89: 231-8. []. [PMID: 23769935].
Kapoor N, Saxena S. Xanthine oxidase inhibitory and antioxidant potential of Indian Muscodor species. 3 Biotech 2016; 6(2): 248-52.
Kumar S, Pagar AD, Ahmad F, et al. Xanthine oxidase inhibitors from an endophytic fungus Lasiodiplodia pseudotheobromae. Bioorg Chem 2019; 87: 851-6. []. [PMID: 30545575].
Shu RG, Wang FW, Yang YM, Liu YX, Tan RX. Antibacterial and xanthine oxidase inhibitory cerebrosides from Fusarium sp. IFB-121, an endophytic fungus in Quercus variabilis. Lipids 2004; 39(7): 667-73. []. [PMID: 15588024].
Tanaka R, Miyata Y, Minakuchi N, Murakami A, Sakazaki F. The xanthine oxidase inhibitory activity and hypouricemic effects of crude drugs obtained from the silkworm in mice. Yakugaku Zasshi 2015; 135(10): 1169-76. []. [PMID: 26423873].
Xu HB, Yang TH, Xie P, et al. Pheophytin analogues from the medicinal lichen Usnea diffracta. Nat Prod Res 2018; 32(9): 1088-94. []. [PMID: 29092623].
Gebhardt P, Dornberger K, Gollmick FA, et al. Quercinol, an anti-inflammatory chromene from the wood-rotting fungus Daedalea quercina (Oak Mazegill). Bioorg Med Chem Lett 2007; 17(9): 2558-60. []. [PMID: 17346963].
Izumida H, Adachi K, Mihara A, Yasuzawa T, Sano H. Hydroxyakalone, a novel xanthine oxidase inhibitor produced by a marine bacterium, Agrobacterium aurantiacum. J Antibiot (Tokyo) 1997; 50(11): 916-8. []. [PMID: 9592563].
Schlegel B, Härtl A, Gollmick FA, Gräfe U. 7-methoxy-2,3-dimethylbenzofuran-5-ol, a new antioxidant from Malbranchea cinnamomea HKI 0286. J Antibiot (Tokyo) 2003; 56(9): 792-4. []. [PMID: 14632290].
Su Q, Su H, Nong Z, et al. Hypouricemic and nephroprotective effects of an active fraction from Polyrhachis vicina Roger on potassium oxonate-induced hyperuricemia in rats. Kidney Blood Press Res 2018; 43(1): 220-33. []. [PMID: 29490297].
Sousa C, Pereira DM, Valentão P, et al. Pieris brassicae inhibits xanthine oxidase. J Agric Food Chem 2009; 57(6): 2288-94. []. [PMID: 19227975].

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