The Protective Effect Of The Total Lignans Of Schisandrin Chinensis For Liver Damage And Its Preliminary Study In Vivo

Liver is the centre of metabolism in human body,it is crucial in protective behavior because of its metabolic conversion and devour detoxification function on the body.At present,the liver disease caused by different kinds of factors,which cause serious damage to human health,is one of the common challenges in the world today.In our country,High rate of liver disease has been the serious problem for pepole health and natiional economy.Schisandra Chinensis is a common TCM for protecting liver funcrtion and has already achieved significant clinical curative efficacy in the treatment of liver disease.The Chinese medicine pharmacokinetic study by virtor of the principle of Pharmacokinetics study to explore the pharmacokinetic hebavior inactive ingredients,effective parts,traditional Chinese medicine(TCM),it has been an essential part of the registration of new dr?g application project and has played an important role in new dr ?g development.This paper established a HPLC-MS method use schisandrin?schisandrol B?schisandtherin?deoxyschisandrin and schisandrin B as index component which were the major hepatoprotective ingredient of the total lignas of Schisandrin Chinensis,to carry out the metabolic regularity study of the total lignas of Schisandrin Chinensis to in vivor,including pharmacokinetics,tissue distribution,and the excetion of the orignal durg form in the urine and feces,so as to provide reference in new durgs of research and development with the total lignas of Schisandrin Chinensis as raw material.The effect of the total ligans of Schisandrin Chinensis to acute alcohol-induced liver damage:Give 56 degrees liquor to the mice for twelve days,on the twelfth day after give the medicine,then take the blood,liver and kidney after sixteen hours.The pathological section have shown that the model of acute alcoholic-induced liver damage was established successfully.On this basis,using the automatic biochemistry analyzer and ultraviolet spectrophotometer to detect the value of serum ALT?AST?SOD?ADH?TBIL?CHO?TG?HDL?LDL and SOD?MDA?ADH on liver to evaluate the effect of liver protection of low,middle and high dose of the total ligans of Schisaindrin Chinensis.The results showed that both middle and high dose of the total ligans of Schisandrin Chinensis have the effect of liver protection,which shown the significant difference compared with the model.and show the dose-dependent effect.Pharmacokinetic studies of the total ligans of Schisandrin Chinensis:a HPLC-MS method was developed and validated for studies of main active lignans in rat plasma,including schisandrin?schisandrol B?schisandtherin?deoxyschisandrin and schisandrin B.The results showed that the developed method conforms to the guiding principles of determination of biosamples and have been applied to comparison research in pharmacokinetic between female and male rats.The atrio ventricular model estimated the main pharmacokinetic parameters;The value of Cmax and AUCO-t in female rats were 2-3 times higher than those in male rats and T1/2?Tmax was significantly longer,but the plasma clearance CL was 2-5 times in male rars compared with female rats;The results demonstrated that the residence time of schisandra ligans was long,the concentration was higher in female compared with male,s?ggestting that it maybe considered that the difference of pharmacology and toxicology between male and female.The tissue distribution of the total ligans of Schisandrin Chinensis in rats:The object established a HPLC-MS analysis method for simultaneous determination of five lignans ingredient of the total lignans of Schisandrin Chinensis in rat tissue,including heart,liver,spleen,lung and klidney.Acorrding to the results of pharmacokinetics,Selecting 2h,3.5h,6h after oral administration of the total lignans of Schisandrin Chinensis as the distribution phase,equilibrium phase and elimination phase to research the effect of tissue distribution in rats.The result shown that the first concentrational lever of five lignins were liver and kidney in rat tissues,followed by lung and heart,the spleen lowest,verifying that the liver might be the effect targer organ;five lignans presented the similar trend in heart?live?spleen?lung?kidney during the all determinational times.Explained the hepatoprotective effect of the total lignan of Schisandrin Chinensis caused by the role of high concentrations and the long duration of action in the liver.The paper on determination of schisandrin?schisandrol B?schisandtherin?deoxyschisandrin and schisandrin B in rat urine and feces to estimate the excretion of the original dr?g form research in rat.The results show that the excretion of the original form was far less than the 50%of dosage in urine and feces after oral administration of the total lignans of Schisandrin Chinensis.Inferring that the main excretion of schisandra lignans form was metabolic elimination In the determination of within 72 h,the excretion trend in urine and feces all over time and balance after rising first,peaked at 24 h.Urine may be the mian excretory pathway of schisandra lignans compared with feces and the total lignans of Schisandrin Chinensis excrete mainly in Metabolic elimiation in the body.To sum up,this topic select the acute alcohol-induced liver damage model as the research object,and verify the hepatoprotective effect of the total ligans of Schisandrin Chinensis;On this basis,the project innovative conduct the elementalmetary study of the total ligans of Schisandrin Chinensis in vivo with HPLC-MS,the systematically carry out the pharmacokinetic?tissue distribution and prototype drug excretion research in the urine and feces in rats.This thesis can provide data support for total wooden fat element as the raw material of traditional Chinese medicine in fructus schisandrae 5 kinds of new drug research and development to provide data support for TCM research and development of class five new dr?g,and guide their application clinical use scientifically,resonably and adequately.