A Efficacy-Toxicity Evaluation Based On The Optimized Model Of Liver Depression In Rats And Bupleuri Radix With Soothing Liver Function

Objective: To optimize the model of liver depression in rats by using the pathogenesis and pathology of traditional Chinese medicine(TCM)and clinical manifestation,and to establish a rat model of liver depression syndrome that were suitable for the efficacy-toxicity evaluation of TCM.At the same time,to evaluate the efficacy and side effects due to soothing the liver of Chaihu in order to provide technical support for the efficacy-toxicity evaluation,and to provide experimental evidence for evaluating the effectiveness of Bupleurum and the safety of clinical drug use.Methods: The rat model was established by the method of rat liver depression syndrome with the effect with efficacy-toxicity evaluation of Bupleurum.Combination of traditional Chinese medicine syndrome points and testing hypothalamic corticotropin(CRH),plasma(ACTH)and corticosterone(CORT)to observe the effects of water extract,alcohol extract and total saponins of Chaihu on liver and depression rats.Calculate each rat liver,spleen and thymus of dirty body ratio,examine each group rats serum AST,ALT,BUN,CR content,and study the efficacy and side effects of different samples of Bupleurum on the rat model of liver depression.Results: Compared with the other modeling methods,the effect of the model by clipping tail four times a day and the neck flails five hours a day was significantly higher than that of the other model.Mainly for the performance: severe hair removal,acute stress mania and chronic stress depression.The fecal hair dry,small,and the number was significantly reduced.The severe peripheral congestion,tail severe ecchymosis.The rats weight growth rate lower than the blank group.The levels of CRH,plasma CORT and ACTH in thalamus were significantly higher than those in normal control group.The positive symptoms of the positive drug group were improved after the drug treatment,and the indexes were also approached to normal group.Bupleurum water extract,alcohol extraction,SSa group,Chaihu Shugan pills weight gain faster than model group,the rat state has improved,the syndrome score was decreased.0.9~3.6 g·kg-1 of water extract of Bupleurum,0.9~3.6g·kg-1 alcohol extract of Bupleurum,18.1~72.4 mg·kg-1 of saikosaponin a significantly improved the liver depression syndrome in rats with liver depression;3.6g·kg-1 water extract of Bupleurum,1.8~3.6g·kg-1 alcohol extract of Bupleurum,and 18.1~72.4 mg·kg-1of saikosaponin a can significantly decreased the contents of CRH,ACTH and CORT in liver depression rats.Under the background of liver depression syndrome,detection of ALT,AST,BUN,Cr indicators of liver and kidneys,3.6 g·kg-1 of water extract of Bupleurum did not show significant side effects of liver and kidneys,1.8~3.6 g·kg-1 of alcohol extract of Bupleurum and 18.1~72.4 mg·kg-1 of saikosaponin a,which has slight liver side effects,did not find significant renal side effects.Conclusions: The model of liver depression syndrome by using the clip tail,the limb bundle and the neck flail is short,the stability is good,the success rate is high,the performance of the model animal the expression and clinical liver depression syndrome animal models have higher consistency.The results showed that Bupleurum had a significant effect on the behavior of rats with liver depression,and the contents of CRH,ACTH and CORT in liver depression rats were significantly decreased,and HPA axis was inhibited.It is suggested that Bupleurum has Shugan Jieyu,the amount of liver qi,anti-liver effect.The mechanism of Bupleurum may be related to the level of ACTH and CORT of rats with liver depression.Among them,only the middle and high dose of Bupleurum extract and Chicken Saponins a had a mild liver toxicity in the rat model of liver depression,Indicating that different samples of Bupleurum in the context of the effective dose within the scope of liver and kidney toxicity decreased.It is suggesting that the role of toxic traditional Chinese medicine in the syndrome itself and the role of normal body state is not the same revealing that reasonable dialectics is one of the important factors to protect the reasonable and safe use of Bupleurum,which is an important basis to explore the scientific connotation of clinical rational drug use based on the efficacy and syndromes of traditional Chinese medicine.