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Xanthine oxidase (EC 1.17.3.2) (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 include 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.
