Xanthine oxidase inhibitor explained

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.^[1] 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,^[2] and tisopurine. Others include febuxostat,^[3] topiroxostat, and inositols (phytic acid and myo-inositol).

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.^{[4] [5]} More generally, planar flavones and flavonols with a 7-hydroxyl group inhibit xanthine oxidase.^[6] An essential oil extracted from Cinnamomum osmophloeum inhibits xanthine oxidase in mice.^[7] 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.^[8] An extract of leaves of Pistacia integerrima also inhibits xanthine oxidase at a level that appears to merit further research.^[9]

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.^[10]

Notes and References

1. Pacher P, Nivorozhkin A, Szabó C . Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol . Pharmacol. Rev. . 58 . 1 . 87–114 . March 2006 . 16507884 . 2233605 . 10.1124/pr.58.1.6 .
2. Iwanaga T, Kobayashi D, Hirayama M, Maeda T, Tamai I . Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone . Drug Metabolism and Disposition . 33 . 12 . 1791–5 . December 2005 . 16135657 . 10.1124/dmd.105.006056 . 16377221 .
3. Becker MA, Schumacher HR, Wortmann RL, etal . 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 . Arthritis and Rheumatism . 52 . 3 . 916–23 . March 2005 . 15751090 . 10.1002/art.20935 .
4. Procházková D, Boušová I, Wilhelmová N . Antioxidant and prooxidant properties of flavonoids . . 82 . 4 . 513–523 . 2011 . 10.1016/j.fitote.2011.01.018 . 21277359.
5. Selloum L, Reichl S, Müller M, Sebihi L, Arnhold J . Effects of flavonols on the generation of superoxide anion radicals by xanthine oxidase and stimulated neutrophils. Archives of Biochemistry and Biophysics. 395. 1. 49–56. November 2001. 11673865. 10.1006/abbi.2001.2562.
6. Nagao A, Seki M, Kobayashi H . Inhibition of xanthine oxidase by flavonoids. Bioscience, Biotechnology, and Biochemistry. 63. 10. 1787–90. October 1999. 10671036. 10.1271/bbb.63.1787. free.
7. 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. 15. 11. 940–5. August 2008. 18693097. 10.1016/j.phymed.2008.06.002.
8. Yoshizumi K, Nishioka N, Tsuji T . 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]. Japanese. Yakugaku Zasshi. 125. 3. 315–21. March 2005. 15738631. 10.1248/yakushi.125.315. free.
9. Ahmad NS, Farman M, Najmi MH, Mian KB, Hasan A . Pharmacological basis for use of Pistacia integerrima leaves in hyperuricemia and gout. J Ethnopharmacol. 117. 3. 478–82. May 2008. 18420362. 10.1016/j.jep.2008.02.031.
10. Chiang HC, Lo YJ, Lu FJ . Xanthine oxidase inhibitors from the leaves of Alsophila spinulosa (Hook) Tryon. Journal of Enzyme Inhibition. 8. 1. 61–71. 1994. 7539070. 10.3109/14756369409040777.