Effects of Toona sinensis Leaf Extract and Its Chemical Constituents on Xanthine Oxidase Activity and Serum Uric Acid Levels in Potassium Oxonate-Induced Hyperuricemic Rats

Abstract

Toona sinensis leaf is used as a seasonal vegetable in Korea. A 70% ethanol extract of these leaves exhibited potent xanthine oxidase (XO) inhibition, with a 50% inhibitory concentration (IC50) of 78.4 µM. To investigate the compounds responsible for this effect, bioassay-guided purification led to the isolation of five constituents, identified as quercetin-3-O-rutinoside, quercetin-3-O-β-d-glucopyranoside, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (compound 3), quercetin-3-O-α-l-rhamnopyranoside, and kaempferol-3-O-α-l-rhamnopyranoside. Compound 3 showed the most potent inhibition of XO, with an IC50 of 2.8 µM. This was similar to that of allopurinol (IC50 = 2.3 µM), which is used clinically to treat hyperuricemia. Kinetic analyses found that compound 3 was a reversible noncompetitive XO inhibitor. In vivo, the T. sinensis leaf extract (300 mg/kg), or compound 3 (40 mg/kg), significantly decreased serum uric acid levels in rats with potassium oxonate-induced hyperuricemia. Furthermore, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis identified a high level of compound 3 in the leaf extract. These findings suggest that T. sinensis leaves could be developed to produce nutraceutical preparations.

Preventive Effects of Fucoidan and Fucoxanthin on Hyperuricemic Rats Induced by Potassium Oxonate

“…(3) Inhibition of uricase activity, which is a common model in rodent experiments. Potassium oxonate (PO), an inhibitor of uricase, can be used to suppress uricase activity through competing with uric acid for binding to uricase [13,14,15]. (4) A hyperuricemia animal model can be obtained by knocking down the uricase gene in rodents [16].…”

From Xanthine Oxidase Inhibition to In Vivo Hypouricemic Effect: An Integrated Overview of In Vitro and In Vivo Studies with Focus on Natural Molecules and Analogues

“…1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose, another glycoside derivative, demonstrated in vitro inhibition of XO activity (IC 50 � 2.8 μM) in a noncompetitive manner (K i � 3.1 μM) with a potency closely to the observed with allopurinol (IC 50 � 2.3 μM). Serum UA levels on hyperuricemic mice at a dose of 40 mg/kg were also lowered [43].…”

Comparative Study of Anti-Gouty Arthritis Effects of Sam-Myo-Whan according to Extraction Solvents

“…The uricase inhibitor PO was injected into rats, to induce hyperuricemia [ 43 ]. The rats were divided into the following seven groups ( n = 6/group): (1) Controls (Con), (2) PO-treated controls, (3) PO+200 mg/kg SMWW, (4) PO+400 mg/kg SMWW, (5) PO+200 mg/kg SMWE, (6) PO+400 mg/kg SMWE, and (7) PO+10 mg/kg allopurinol (AP).…”