Xanthine oxidase inhibitor
{{Short description|Substance inhibiting xanthine oxidase}}
A xanthine oxidase inhibitor is any substance that inhibits the activity of xanthine oxidase, an enzyme involved in purine metabolism. In humans, inhibition of xanthine oxidase reduces the production of uric acid, and several medications that inhibit xanthine oxidase are indicated for treatment of hyperuricemia and related medical conditions including gout.{{cite journal |vauthors=Pacher P, Nivorozhkin A, Szabó C | title = Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol | journal = Pharmacol. Rev. | volume = 58 | issue = 1 | pages = 87–114 |date=March 2006 | pmid = 16507884 | pmc = 2233605 | doi = 10.1124/pr.58.1.6 | url = }} Xanthine oxidase inhibitors are being investigated for management of reperfusion injury.
Xanthine oxidase inhibitors are of two kinds: purine analogues and others. Purine analogues include allopurinol, oxypurinol,{{cite journal |vauthors=Iwanaga T, Kobayashi D, Hirayama M, Maeda T, Tamai I |title=Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone |journal=Drug Metabolism and Disposition |volume=33 |issue=12 |pages=1791–5 |date=December 2005 |pmid=16135657 |doi=10.1124/dmd.105.006056 |s2cid=16377221 }} and tisopurine. Others include febuxostat,{{cite journal |vauthors=Becker MA, Schumacher HR, Wortmann RL, etal |title=Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout |journal=Arthritis and Rheumatism |volume=52 |issue=3 |pages=916–23 |date=March 2005 |pmid=15751090 |doi=10.1002/art.20935 }} topiroxostat, and inositols (phytic acid and myo-inositol{{Citation needed|date=December 2014}}).
In experiments, numerous natural products have been found to inhibit xanthine oxidase in vitro or in model animals (mice, rats). These include three flavonoids that occur in many different fruits and vegetables: kaempferol, myricetin, and quercetin.{{cite journal | vauthors=Procházková D, Boušová I, Wilhelmová N | title=Antioxidant and prooxidant properties of flavonoids | journal=Fitoterapia | volume=82 | issue=4 | pages=513–523 | year=2011 | doi = 10.1016/j.fitote.2011.01.018 | pmid=21277359| doi-access= }}{{cite journal
|vauthors=Selloum L, Reichl S, Müller M, Sebihi L, Arnhold J | title = Effects of flavonols on the generation of superoxide anion radicals by xanthine oxidase and stimulated neutrophils
| journal = Archives of Biochemistry and Biophysics
| volume = 395
| issue = 1
| pages = 49–56
|date=November 2001
| pmid = 11673865
| doi = 10.1006/abbi.2001.2562
| url =
}} More generally, planar flavones and flavonols with a 7-hydroxyl group inhibit xanthine oxidase.{{cite journal
|vauthors=Nagao A, Seki M, Kobayashi H | title = Inhibition of xanthine oxidase by flavonoids
| journal = Bioscience, Biotechnology, and Biochemistry
| volume = 63
| issue = 10
| pages = 1787–90
|date=October 1999
| pmid = 10671036
| doi = 10.1271/bbb.63.1787
| url =
| doi-access = free
}} An essential oil extracted from Cinnamomum osmophloeum inhibits xanthine oxidase in mice.{{cite journal
|vauthors=Wang SY, Yang CW, Liao JW, Zhen WW, Chu FH, Chang ST | title = Essential oil from leaves of Cinnamomum osmophloeum acts as a xanthine oxidase inhibitor and reduces the serum uric acid levels in oxonate-induced mice
| journal = Phytomedicine
| volume = 15
| issue = 11
| pages = 940–5
|date=August 2008
| pmid = 18693097
| doi = 10.1016/j.phymed.2008.06.002
| url =http://ntur.lib.ntu.edu.tw//bitstream/246246/177305/1/20.pdf
}} The natural product propolis from selected sources inhibits xanthine oxidase in rats; the specific substance responsible for this inhibition has not been identified, and the generality of these findings is unknown.{{cite journal
|vauthors=Yoshizumi K, Nishioka N, Tsuji T | title = プロポリスのキサンチンオキシダーゼ活性阻害作用及び血漿尿酸値低下作用 [Xanthine oxidase inhibitory activity and hypouricemia effect of propolis in rats]
| language = Japanese
| journal = Yakugaku Zasshi
| volume = 125
| issue = 3
| pages = 315–21
|date=March 2005
| pmid = 15738631
| doi = 10.1248/yakushi.125.315
| doi-access = free
}} An extract of leaves of Pistacia integerrima also inhibits xanthine oxidase at a level that appears to merit further research.{{cite journal
|vauthors=Ahmad NS, Farman M, Najmi MH, Mian KB, Hasan A | title = Pharmacological basis for use of Pistacia integerrima leaves in hyperuricemia and gout
| journal = J Ethnopharmacol
| volume = 117
| issue = 3
| pages = 478–82
|date=May 2008
| pmid = 18420362
| doi = 10.1016/j.jep.2008.02.031
| url =
}}
In folk medicine the tree fern Cyathea spinulosa (formerly Alsophila spinulosa) has been used for gout, but its most active component, caffeic acid, is only a weak inhibitor of xanthine oxidase.{{cite journal
|vauthors=Chiang HC, Lo YJ, Lu FJ | title = Xanthine oxidase inhibitors from the leaves of Alsophila spinulosa (Hook) Tryon
| journal = Journal of Enzyme Inhibition
| volume = 8
| issue = 1
| pages = 61–71
| year = 1994
| pmid = 7539070
| doi = 10.3109/14756369409040777
| url =
}}