| Objective:Valeriana jatamansi Jones named Zhizhuxiang in China is one of the most popular botanical drugs in the folk, which is widely used by over ten Chinese Minorities to treat the malaise, abdominal distention and pain, insomnia, rheumatism, etc. To date there is rarely evidence corroborating the safety of its iridoid effective fraction. This study aims at determining the toxicity profile of iridoid effective fraction from V.jatamansi J.(IEFV).To evaluate the safety of IEFV and provide the data for the clinic application.Materials:The acute and sub-chronic toxicity of IEFV were investigated by employing established methods. The acute toxicity study was done by oral administering single dose (3200mg/kg body weight) of IEFV whose vehicle used for dilution was the mixture of0.5%CMC-Na and99.5%water to adult mice,while consecutively observing mice weight, diet, toxic reaction and death for14days. In the sub-chronic toxicity study, low doses (24mg/kg.bw), middle doses (96mg/kg.bw), high doses (120mg/kg bw) of IEFV were administered daily to adult rats for6days a week except Sunday during the three months. The general behavior of the rats was observed and recorded every day. The weight and food consumption of rats were tested every week. The effect on organs, the hematological and blood biochemical parameters and histopathology were assessed at the time of the1.5th month (five male and five female) and the3rd month (ten male and ten female).The remaining ten rats (five male and five female) of each group were fed for two weeks to observe reversible and delayed toxicity after the medicine administrated.Results:Acute toxicity study There was no significant difference of the body weight of mice between the control group and drug group (P>0.05):the maximum tolerated dose (MTD) of IEFV on mice is3200mg/kg.Sub-chronic toxicity study On rats, daily single oral doses of the IEFV did not result to death or the general behavior including appearance signs, activities, discharge and waste at all tested doses. There was no significant difference(P>0.05) in rats body weight between the drug groups and the control group, but had an effect on food consumption(P<0.05)only in the first three weeks which were caused by the rats’transient. As the animals adapt to the environment, the difference of food consumption was not observed. Some differences were observed in hematological parameters.The Ret of female rats from high doses was higher(P<0.05) which were caused by the rats’transient in the mid time. In the end time, the MCV and MCH of female rats from low doses were higher (P<0.01) and the N and the L of female rats from high doses were higher (P<0.05) than that of in the control group. But they were all in the normal range. For the blood biochemical parameters, the GLU (P<0.05) of female rats in mid time and the Urea (P<0.01) of male rats from mid doses were lower. But they were both in the normal range. The TBIL of male rats from high doses was higher(P<0.05) but that of in mid doses was lower than control doses.It means there was no dose-effect relationship. For generally, no statistically significant differences (P>0.05) no abnormality of other organs were noted in both gross and histopathological examinations except several animal transient(P<0.05) or spontaneous lesions(abnormality).Conclusion:The IEFV is very safe in the usual clinical dose. IEFV may not have any single dose toxicity. The no-observed adverse effects level (NOAEL) is considered to be120mg/kg/day for rats. There is no direct correlation between the hematology, blood biochemical indexes, organ coefficient of tested rats and the toxicity of the IEFV. |
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