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

Abstract

: 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.

Palmatine Protects Against MSU-Induced Gouty Arthritis via Regulating the NF-κB/NLRP3 and Nrf2 Pathways

“… 18 , 19 It has been also found to be a xanthine oxidase inhibitor with potential application in the treatment of hyperuricemia. 20 However, whether PAL could alleviate inflammatory response on MSU-induced gouty arthritis was unclear. Therefore, the present study made a pioneering endeavor to explore the potential effect and underlying mechanism of PAL in LPS plus MSU crystal-induced inflammation in THP-1 cells, and MSU crystal-induced gouty arthritis in mice.…”

Flavonoids: Antiplatelet Effect as Inhibitors of COX-1

“…The classification of flavonoids is quite broad and is carried out according to the constituents present in their chemical structure, and is divided into flavonols, flavones, flavanones, flavanols, isoflavones, anthocyanidins, dihydroflavonols, and chalcones [ 8 ]. These compounds play a very important role in a series of physiological and biochemical processes as they act as antioxidants [ 9 ], inhibitors of enzyme systems [ 10 ], and precursors of toxic substances and pigments [ 11 ], as well as being involved in the defense against infections [ 12 , 13 ], in the modulation of the inflammatory response, and of course in platelet aggregation [ 14 ].…”

The Association of Oxidative and Antioxidant Potential with Cardiometabolic Risk Profile in the Group of 60- to 65-Year-Old Seniors from Central Poland

“…In our previous study, we stated that uric acid is one of many factors decreasing platelet reactivity [ 24 ]. However, xanthine oxidase can play the role of oxidant enzyme that oxidizes thiol groups under certain stress conditions in the tissue [ 57 ]. The role of uric acid appears to be complex and multidirectional.…”