Hypouricemic effect and acute toxicity of lovage leaf extract (Levisticum officinale Кoch)

Abstract

The aim of the study is to find out the effect of a liquid hydroalcoholic extract of lovage leaf (ELL) on the metabolism of uric acid (UA) in normal conditions and in a model of hyperuricemia, and to determine the acute toxicity of this extract. ELL was obtained by percolation, 70 % ethanol was used as an extractant. In an experiment on mice, the effect of a 7-day administration of ELL (from which the alcohol was preliminarily distilled off and the volume restored with water) was determined at doses of 1 ml/kg and 5 ml/kg on the content of UA in the blood, on the renal excretion of UA in intact mice and on models of hyperuricemia caused by potassium oxonate, as well as xanthine oxidase (XO) activity in the liver. Allopurinol (10 mg/kg in the stomach) was used as a reference drug. Correlations between the indicators of purine metabolism were analyzed. The acute toxicity of ELL was determined by the express method. Alcohol-deprived ELL in intact animals had a moderate, and in the model of oxonate-induced hyperuricemia, a more pronounced hypouricemic effect (at a dose of 5 ml/kg, it reduced the content of UA in the blood by 47 %, p < 0.01). In terms of the severity of the hypouricemic effect, ELL was inferior to allopurinol. The mechanism of the hypouricemic effect of ELL, as well as allopurinol, is the inhibition of XO (enzyme activity decreased by 37–51 % with normouricemia and by 51–57 % with hyperuricemia). The role of this mechanism is confirmed by the results of the correlation analysis of the relationship between uricemia and XO activity. Both ELL at a dose of 5 ml/kg and allopurinol in the conditions of the oxonate-induced model of hyperuricemia restored a direct correlation between the blood concentration of UA and the activity of XO (ρ = 0.68 and ρ = 0.88, respectively), inherent in intact animals (ρ = 0.86) and impaired by potassium oxonate (ρ = –0.04). Renal excretion of UA under the influence of ELL decreased. ELL belongs to practically non-toxic substances (toxicity class V, 5000 < LD50 < 15 000 mg/kg when determined by the express method). Thus, ELL can be considered as a promising hypouricemic agent for the treatment of diseases associated with an increase in the level of UA in the blood.