Mechanism of flavonoids inhibiting xanthine oxidase and alleviating hyperuricemia from structure–activity relationship and animal experiments: A review

Abstract

Hyperuricemia (HUA) is a metabolic disease caused by excessive uric acid in patients. Flavonoids have attracted extensive attention due to their safety, effectiveness, and little side effects in the treatment of HUA and inhibition of xanthine oxidase (XO) activity. In this paper, the studies on the treatment of HUA and the inhibition of XO activity by flavonoids (including flavones, flavonols, flavanones, flavanols, isoflavonoids, anthocyanins, and chalcones) were comprehensively reviewed from the aspects of structure–activity relationship and animal experiments. Results showed that hydrogen bonds and hydrophobic interactions were the two most important forces involved in the interaction between flavonoids and XO. Flavonoids could combine with the hydrophobic cavity of XO to cause changes in XO structure and influence the action of enzyme and substrate, thereby decreasing the catalytic activity of XO. Moreover, flavonoids undergo a series of metabolic reactions in the organism, which plays a role in alleviating HUA by affecting the expression of related genes and proteins (e.g., glucose transporter 9, urate transporter 1, and organic anion transporter 1) in the kidneys, liver, and intestinal tract of the organism and changing the internal environment in organs. In addition, this paper provides new perspectives on the shortcomings of the current research, to promote the in‐depth development and application of flavonoids.

Chemotaxonomy in the Etlingera Genus from Sulawesi, Indonesia: Design and molecular docking of antioxidant marker

“…Both compounds (Yakuchinone A and Yakuchinone B) exhibited tight binding to critical amino acids, particularly those involved in substrate binding (Arg880, Val1011) and catalysis (Glu802, Glu1261), potentially inhibiting xanthine oxidase enzymatic activity. If the compounds compete with substrates for binding or disrupt the catalytic mechanism, they could effectively reduce the conversion of xanthine to uric acid and Reactive Oxygen Species (ROS) (Xue et al 2023). Furthermore, Yakuchinone A and Yakuchinone B each possess a hydroxyl group on their benzene ring.…”

Screening for Anti-Hyperuricemia Potential of Some Indonesian Medicinal Plants Through Xanthine Oxidase Inhibition in Vitro Assay

“…This assumption is based on research that states that flavonoids and phenolic acid can mainly reduce uric acid levels in the serum of hyperuricemia rats by inhibiting xanthine oxydase activity and regulating urate transporters in the kidney. Flavonoids and phenolic acid prevent the pathological process of hyperuricemia by regulating biomarkers related to purine metabolism, amino acid metabolism, and lipid metabolism [28,30,39].…”

Phytochemical profile, in vitro anti‐inflammatory, and anti‐xanthine oxidase activity of durian fruit rind fractions (Durio zibethinus)

“…Notably, flavonoid compounds such as phlorizin and four different quercetin derivatives (quercetin-3-O-arabinoside, quercetin glucoside, quercetin-3-O-(6 00 -trans p-coumaroyl-2 00 -gly) Rh, and dihydroquercetinglucosyl-rhamnosyl) were identified in fraction F2 (Table 4). Previous studies have emphasised the inhibitory activity of flavonoid-chalcone and -flavonols on inflammation and XO (Nagao et al, 1999;Al-Khayri et al, 2022;Kobzar et al, 2023;Xue et al, 2023). Bhatt et al (2021) highlighted the potential anti-inflammatory properties of quercetin glucoside extracted from fresh fenugreek leaves (Trigonella foenum-graecum), citing its efficacy in inhibiting LOX and hyaluronidase enzymes.…”