Acute and sub-chronic oral toxicity profiles of the aqueous extract of Cortex Dictamni in mice and rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cortex Dictamni is used in Chinese folk medicine for the treatment of jaundice, cough, rheumatism and some skin diseases; however, its possible toxicity has not been rigorously studied. The present investigation was carried out to evaluate the safety of Cortex Dictamni aqueous extract (CDAE) by acute and sub-chronic toxicity studies. MATERIALS AND METHODS: In acute toxicity tests, seven groups of mice (n=5/group/sex) were orally treated with doses of 0, 28.7, 33.6, 39.7, 46.7, 54.9 and 64.6g/kg of CDAE and general behavior, adverse effects and mortality were recorded for up to 14 days. In sub-chronic toxicity assays, animals received CDAE by gavage at the doses of 0, 3.0, 6.0 or 12.0g/kg/day (n=10/group/sex) for 4 weeks and then followed for a 2-week recovery period. The biochemical, hematological and morphological parameters were determined. RESULTS: In adult mice, single oral administrations of CDAE (0-64.6g/kg body weight) induced an increase in the incidence of general behavioral adverse effects. The mortality rate also increased with increasing dosage (LD50=48.2g/kg). In rats, daily single oral doses of CDAE were well tolerated behaviorally after 4 weeks and induced no significant changes in body weights. However, the absolute and relative liver weight at the end of both administration and recovery periods were significantly elevated, although the histological examination of various organs revealed no differences between the control and the treated groups. The hematological and biochemical parameters were significantly changed; lymphocytes, alanine transaminase, alkaline phosphatase levels showed a significant decrease while neutrophilic granulocyte, albumin, total cholesterol, glucose and blood urea nitrogen levels showed a significant increase, suggesting disturbances of hematopoiesis and liver and kidney functions. CONCLUSIONS: Overall, the acute toxicity of CDAE was not clearly observed. However, it is possible that CDAE has a selective toxicity considering the changes in some hematological and liver function parameters and the liver-body weight ratios in the sub-chronic oral toxicity study.

[Pharmacokinetics of Guizhi Fuling capsule in Beagle dogs].

OBJECTIVE: To investigate pharmacokinetic parameters of peoniflorin, albiflorin and amygdaloside after administration of Guizhi Fuling capsule in beagle dogs. METHOD: Plasma was collected from forelimb vein of Beagle dogs after oral administration of Guizhi Fuling capsule. HPLC-MS/MS method was used to determine the concentrations of constituents in plasma. The pharmacokinetic parameters were analyzed by program DAS 2.0. RESULT: The limit of quantitation of peoniflorin, albiflorin and amygdaloside were 0.25, 2.64, 0.04 microg x L(-1), respectively. After administrated with different doses, half-life of peoniflorin in dogs were 4.33, 3.62 h, albiflorin were 6.16, 5.91 h, amygdaloside were 2.43, 1.32 h. The AUC(0-t) of all components were related to dose. CONCLUSION: The pharmacokinetic course of peoniflorin, albiflorin and amygdaloside can be described by two-compartment model, and these components have high expose.