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

This was just published in Current Pharmaceutical Design:

Xanthine oxidase (EC 1.17.3.2) (XO) is among the main enzymatic sources that produce 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 substance in purine catabolism, first to xanthine and then to uric acid. XO becomes an oxidant enzyme that oxidizes thiol groups under certain stress conditions in the tissue. The last metabolic step, in which hypoxanthin becomes uric acid, is catalyzed by XO. Uric acid, considered a waste product, can cause kidney stones and gouty-type arthritis as it is taken shape, when present in high concentrations. Therefore, XO inhibitors are one of the drug classes utilized against gout, a purine metabolic process disease that causes urate crystal storage in the joint and its environments triggered by hyperuricemia. Urate-lowering treatment consist of XO inhibitors that decrease uric acid production as well as uricosuric drugs that increase urea excretion. Current drugs that block uric acid synthesis through XO inhibition are uricase, allopurinol, and febuxostat. Considering that the side results, security and tolerability issues of some current gout medications still exist; intensive research study is ongoing to look for new, reliable, and safer XO inhibitors of synthetic or natural origins for the treatment of the disease. In the present evaluation, we aimed to examine in information XO inhibitory capacities of pure natural substances along with the extracts from plants and other natural sources through screening Pubmed, Web of Science (WoS), Scopus, and Google Academic. The data mentioned to the reality that natural items, especially 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 prospective for new XO inhibitors efficient in usage against gout disease. In addition, not just plants however other biological sources such as microfungi, macrofungi, lichens, bugs (silk worms, ants, etc) appear to be the appealing sources of novel XO inhibitors.

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