Comparative Studies On The Toxicity Change Of The Crude,Processed Of Fructus Xanthii

Objective:Comparative studies on the toxicity effects of the crude and processed Fructus Xanthii. The toxicity changes of Fructus Xanthii and processed Fructus Xanthii were studied, to provide scientific basis for clinical safety and rational use of drugs.Methods:1. Determination of chemical compositions:High performance liquid chromatography was used to determine the contents of effective components, toxic components ?CATR and ATR? in samples.2. Acute toxicity test of mice ?in vivo?:Referring to the mouse acute systemic toxicity test methods,the lethal median dose of Fructus Xanthii and processed Fructus Xanthii were determined. Watch closely the death situation and toxic symptoms after administration.3. Complete acute toxicity test in rats ?in vivo?:According to the method of complete acute toxicity testrats in different groups were given different concentrations of drugs respectively according to lml/100g weight. Rats were weighed in 1st,3rd,7th and 14th days.Food intake were measured in 0,1st, 2nd days. The toxic reaction of animals in each group was observed.Ten rats of each group were killed on third days and fourteenth days after administration, blood and blood biochemistry indexes were determined, and the main organs were dissected,observed and calculated organ index.4.Microtox test ?in vitro?: ? The 1%-100% inhibitory rate of the crude and processed of Fructus Xanthii were obtained respectively from preliminary experiments;?On the basis of pre-experiments, the formal experiment was carried out according to the optimal system detection method of the luminescent bacteria-Each sample was repeated three times. Drawed the corresponding toxic dose effect dynamic curve, and calculated the inhibition rates. The IC₅₀ value of the luminescent bacteria was obtained, and the toxicity of each sample was compared with the IC₅₀value.Results:1.Chemical composition determination:the total conent of atractyloside toxic components in the crude and processed of Fructus Xanthii were 0.722,1.165mg/g respectively?Contents of ATR were 0.257,0.874mg/g respectively; contents of CATR were 0.465.0.291 mg/g respectively?. The main effective components of the crude and processed of Fructus Xanthii have been measured, contents of neochlorogenic acid were 0.323,0.767mg/g respectively; contents of chlorogenic acid were 0.318,0.679mg/g respectively;contents of implicit chlorogenic acid were 0.210 and 0.482mg/g respectively.2.Acute toxicity test of mices ?in vivo?:Similar symptoms of toxicity in mices after giving medicine, were static prone, respiratory inhibition, piloerection, tail cyanosis, intermittent convulsions, turn right reflex disappearance etc..The half lethal dose ?LD50? of the crude, processed a of Fructus Xanthii were 367.8g/kg,182.3g/kg.Acute toxicity test of mice?in vivo?:Similar symptoms of toxicity in mice after giving medicine, were static prone, respiratory inhibition, piloerection, tail cyanosis, intermittent convulsions, turn right reflex disappearance etc..The half lethal dose ?LD50? of the crude, processed of Fructus Xanthii were 367.8g/kg,182.3g/kg respectively.3. Complete acute toxicity test in rats:?1? The crude Fructus Xanthii ?Compared with the blank control group, general symptoms, body weight and food intake in every different dosage group had no statistical significance ?P> 0.05?.?The index of blood cytology:After 3 days administration, the MONO?%? in 83.33g ?crude drug?/kg dose group compared with the control group decreased ?P?0.05?. At 14th days after administration, the PLT in all dosage groups and PCT in high dosage group increased, statistical discrepancy was significant?P<0.05 or P?0.01?. ?The blood biochemistry index:After 3 days administration, TBIL decreased in 83.33g ?crude drug?/kg dose group; TG increased in 41.67g ?crude drug?/kg dose group; TP, GLU, CK and GLOB increased in 20.83g ?crude drug?/kg dose group, compared with the control group there were significant difference ?P?0.05?. After 14 days administration, TBIL increased in 83.33g ?crude drug? /kg dose group; TG increased and BUN decreased in 20.83,41.67g ?crude drug?/kg dose groups ?P<0.01?.?The organ index:After 3 days administration, compared with control group, there was no significant difference in each dose group of medicinal organ index. After 14 days administration, the thymus index increased in 83.33g ?crude drug? /kg dose group compared with the control group ?P?0.05?.?2? Processed Fructus Xanthii ?Compared with the blank control group, general symptoms, body weight and food intake in every different dosage group had no statistical significance ?P>0.05?.?The index of blood cytology:After 3 days administration, compared with the control group, the WBC,NEUT,LYMPH,EO, MONO increased in 72.92g ?crude drug?/kg dose group. The NEUT increased in 18.23g ?crude drug?/kg dose group ?P<0.05 or P?0.01?. After 14 days administration, compared with the control group RBC, HGB, PLT, PCT increased in 36.46g ?crude drugs?/kg dose group ?P<0.05 or P?0.01?.?The blood biochemistry index:After 3 days administration, compared with the control group, the TG of 36.46g ?crude drug? /kg dose group increased ?P<0.05?.After 14 days administration, compared with the control group, GLOB increased and A/G decreased in 72.92g ?crude drugs?/kg dose group, BUN decreased in the 18.23g ?crude drugs?/kg dose group the?P<0.05?.?The organ index:After 3 days administration, compared with the blank control group, the thymus index of 72.92g ?crude drugs?/kg dose group increased ?P?0.01?. After 14 days administration, there was no statistical difference with organ index.4. Microtox test ?in vitro?:Half inhibitory concentration (IC₅₀) in luminescent bacteria of the crude and processed of Fructus Xanthii were 27.0892,11.2826mg/ml respectively.Conclusion:1 Both the Acute toxicity test of mice ?in vivo? and Microtox test ?in vitro? indicated that higher toxicity of processed Fructus Xanthii than crude Fructus Xanthii.2 Complete acute toxicity test in rats?in vivo? showed that, disposable gastric lavage administration within the range of experiment doses,no clinically significant changes were detected about detection indexs.