Abstract: Objective To investigate the chronic toxicity of Hypericum perforatum extract through oral administration for 9 months on Beagle dogs. Methods Twenty-eight Beagle dogs were randomly divided into blank control group and low, middle and high dose groups,which were treated respectively with Hypericum perforatum extract (0.3, 0.55, 1.0 g/kg) by oral administration, once a day, 6 times weekly for 38 weeks. During the whole experimental period, the Beagle dogs were treated with Hypericum perforatum extract through deglutiatur administration once a day for successive 38 weeks, meanwhile the activities of the dogs were observed once a day, the body weight were weighed weekly. Electrocardiographic examination, blood counts determination, serum biochemical measurement, urinalysis test and histomorphologic observation were conducted on the 10th, 20th, 30th, 38th week with successive administration and on the 46th week without administration for 8 weeks. Some animal in each group were sacrificed, whose organs and tissues were harvested, of which the main ones were weighted and examined histopathologically on the 20th, the 38th week with administration and the 46th week without administration for 8 weeks. Results During the whole experimental period, the animal activities, electrocardiographic examination, blood counts determination and urinalysis test showed no obvious abnormalities. But ALP increased in blood of the Beagle dogs in the 1.0 g/kg groups on the 20th and the 30th week with administration, TBIL increased in the 0.55 g/kg and 1.0 g/kg groups on the 38th week (P<0.05 or P<0.01). Meanwhile, liver coefficient increased in the 1.0 g/kg groups (P<0.05) on the 20 th, 38th week after administration. Pathological examination showed that slightly granular degeneration appeared in the liver cells of 2 animals (1♀,1♂) and in the renal tubules of 1 animal (♀) in the 1.0 g/kg groups on the 20th and 38th weeks, regardless of sex. There was no significant difference between the rest of the treatment groups and the corresponding control group in hematological and serum biochemical indexes, the organ coefficient, the morphological changes (P>0.05). Conclusion Some mild toxic effects on the liver and kidney function or organization were found on the 20th and 38th week when the Beagle dogs were treated with Hypericum perforatum extract (0.55, 1.0 g/kg) through successive oral administration once a day for 38 weeks , but could disappear gradually over time after withdrawn. The degree of toxicity was positively correlated with the dose of administration and the medication cycle. The safe dosage of Hypericum perforatum extract by intragastric administration is 0.3 g/kg, equivalent to 40 times of clinical depression treatment dose.

Key words: Hypericum perforatum L, Chronic toxicity test, Liver toxicity, Renal toxicity