Study on Compatibility Proportion of Mongolian Medicine “Terminalia chebula Decomposing Poison of Aconitum kusnezoffii ” / 中国药房

ABSTRACT

OBJECTIVE： To investigate the best compatibility proportion of Mongolian medicine “Terminalia chebula decomposing the poison of Aconitum kusnezoffii”. METHODS： Totally 40 rats were randomly divided into blank control group （0.05％ CMC-Na）， raw A. kusnezoffii group （0.12 g/kg by crude drug） and raw A. kusnezoffii-T. chebula  （1 ∶ 3，1 ∶ 1，3 ∶ 1， mass ratio） group （0.12 g/kg raw A. kusnezoffii by raw material）， 8 rats in each group. They were given relevant medicine intragastrically once a day， for consecutive 28 d. 0.5 h after last medication， serum contents of cTn-I and MB were determined， and the changes of cardiological structure were observed； the detoxification effects of T. chebula on cardiotoxicity induced by A. kusnezoffii were investigated. Binding rates of 3 kinds of aconitine （concentrations of aconitine， mesaconitine and hypaconitine were 5， 10， 20， 40， 80， 160， 400 ng/mL） to binding rate of plasma protein with normal human plasma were determined by equilibrium dialysis combined with liquid chromtography-mass spectrometry. The concentrations of 3 kinds of aconitine were fixed as 100 ng/mL. After adding main detoxification component tannic acid in different proportions of T. chebula （1 ∶ 0.025， 1 ∶ 0.075， 1 ∶ 0.1， 1 ∶ 0.5）， the effects of them on plasma protein binding rate of 3 kinds of aconitine were investigated； the possible mechanism  of T. chebula decomposing the poison of A. kusnezoffii inducing cardiotoxicity were investigated. RESULTS： In detoxification experiment， compared with blank control group， serum contents of cTn-I and MB were increased significantly in raw A. kusnezoffii group （P＜0.05）. There were obvious pathological changes in myocardial tissue， such as disorder of cell arrangement， cell shrinkage and cytoplasm staining. Compared with raw A. kusnezoffii group， serum contents of cTn-I and MB in raw A. kusnezoffii-T. chebula （1 ∶ 3， 1 ∶ 1， 3 ∶ 1） groups were decreased significantly （P＜0.05）， and there was no significant difference between the raw A. kusnezoffii-T. chebula （3 ∶ 1， 1 ∶ 1） groups and blank control group （P＞0.05）； myocardial pathological changes were improved to varying degrees. The structure of myocardial tissue in raw A. kusnezoffii-T. chebula （3 ∶ 1） groups were similar to blank control group. In the mechanism investigation experiment under the condition of different concentrations， plasma protein binding rates of 3 kinds of aconitine with normal human plasma were about 30％， without statistical significance （P＞0.05） and significant concentration-dependent manner. After adding tannic acid， plasma protein binding rate of 3 kinds of aconitine in A. kusnezoffii was decreased to different extent； when 3 kinds of aconitine were combined with tannic acid in the ratio of 1 ∶ 0.1， 1 ∶ 0.075 and 1 ∶ 0.5， the plasma protein binding rate decreased significantly （P＜0.05）， in proportion-dependent manner. CONCLUSIONS： Compatible use of raw A. kusnezoffii-T. chebula （3 ∶ 1） show that best detoxification effect on A. kusnezoffii-induced cardiotoxicity. Under this compatibility ratio， the plasma protein binding rate of 3 kinds of aconitine in A. kusnezoffii with normal human plasma is relatively high and the free drug concentration is relatively low.