Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity

Figures & data

Table 1. Chemical structures of mangiferin and its analogues.

Chemical structure	Compound	Molecular formula	R1	R2	R3	R4	R5	R6
	1	C19H18O11	OH	Glucose	OH	OH	OH	H
	2	C13H8O6	OH	H	OH	OH	OH	H
	3	C16H12O8	OH	R2 +R3 = OCH2O		OH	OMe	OMe
	4	C16H14O7	OMe	OMe	OMe	OH	H	OH
	5	C15H12O7	OH	OMe	OH	OH	OMe	H
	6	C16H14O8	OH	OMe	OH	OH	OMe	OMe
	7	C16H14O6	OMe	OMe	OH	H	OMe	H
	8	C15H12O6	OH	OMe	OMe	H	OH	H
	9	C17H16O6	OMe	OMe	OMe	H	OMe	H

Figure 1. Effects of intragastric administration of compounds 1 and 2 on serum uric acid levels in uricase inhibitor potassium oxonate-treated mice. CON, normal control; M, hyperuricaemic control. The data are expressed as the means ± SD for 10 mice per group. ^ap < 0.05 or less versus the control group; ^bp < 0.05 or less versus the hyperuricaemic group; ^cp < 0.05 or less versus the compound 1 (1.5 mg/kg) treated group; ^dp < 0.05 or less versus the compound 2 (0.93 mg/kg) treated group; ^ep < 0.05 or less versus the allopurinol-treated group (Dunnett’s test).

Table 2. Effects of compounds 1 and 2 on serum uric acid levels in the hyperuricaemic mice induced by uricase inhibitor potassium oxonate: a time-course study.

			Serum uric acid (μmol/L)
Group	Dose (mg/kg μmol/kg)	Treatment	30 (min)	60 (min)	90 (min)
Control	0.5%CMC-Na	ig	96.8 ± 22.2	94.2 ± 18.7	97.8 ± 19.0
Hyperuricaemia	0.5%CMC-Na	ig	146.8 ± 17.8^a	149.2 ± 15.3^a	148.8 ± 12.5^a
Hyperuricaemia + compound 1	3.0 7.1	ig	97.5 ± 15.7^b	101.9 ± 22.3^b	115.8 ± 15.1^a^b
Hyperuricaemia + compound 2	1.85 7.1	ig	104.2 ± 12.6^b	96.2 ± 15.9^b	112.2 ± 20.9^a^b
Control	1% PEG-400	iv	98.3 ± 28.1	95.3 ± 21.2	96.7 ± 20.2
Hyperuricaemia	1% PEG-400	iv	147.2 ± 38.5^a	146.5 ± 23.5^a	144.5 ± 26.7^a
Hyperuricaemia + compound 1	3.0 7.1	iv	113.8 ± 12.4^a	95.1 ± 22.8^b	113.2 ± 19.0
Hyperuricaemia + compound 2	1.85 7.1	iv	97.7 ± 19.3^b	92.1 ± 26.5^b	95.6 ± 23.1^b

Data are expressed as means ± SD for 10 mice in each group.

^ap < 0.05 or less versus the control group;

^bp < 0.05 or less versus the hyperuricaemic group (Dunnett’s test).

Figure 2. Inhibition of xanthine oxidase by compounds 1–9. (A) IC₅₀, inhibitory type and Kies values of test compounds. (B–E) Concentration-dependent xanthine oxidase (XO) inhibition by compounds 2, 5, 6 and allopurinol. Data presented are the mean values ± SD. for eight independent experiments. (F–L) Inhibition kinetics of xanthine oxidase by compounds 2, 5, 6 and allopurinol. Each point is the average value from three independent experiments.