Pharmacokinetic And Pharmacodynamic Study Of The Three Yellow Square Anti-endotoxin Activity

San-Huang Formula was firstly recorded in "Jingui Chamber",composed by Radix et Rhizoma Rhei,Rhizoma Coptidis and Radix Scutellariae,with the function of clearing heat-fire,removing dampness and removing toxin,for the treatment of heat-toxin syndrome,which is similar to endotoxemia.According to the characteristics of the principle of the treatment of heat-toxin syndrome,the method of clearing heat and removing toxin is constantly applied.Under the guidance of TCM theory,this paper is based on the research ideas that San-Huang Formula can treat endotoxemia, obeyed the principles of the combination of disease and syndrome,the relevance of formula and syndrome,the correspondence of drug and syndrome,and the unification of theory,method,formula and drug.OBJECTIVERegarding the anti-toxin activity as the breakthrough point,this article had studied pharmacokinetics and pharmacodynamics of anti-endotoxemia of series of San-Huang preparations,and also compared anti-endotoxin activity,in order to reveal the relationship between effective components and effect of San-Huang Formula, elucidate its mechanism and provide scientific basis for the clinical application.METHODS1 San-Huang Formula anti-endotoxin activity in vitro and chemical fingerprintsCompared with the anti-endotoxin activity in vitro of the different prescriptions of 12 manufacturers of San-Huang Formula,and preliminarily studied chemical fingerprints as well,all the major peaks had been confirmed by the method of the dynamic turbidity,with cluster analysis and principal component analysis to process statistical data.2 the pharmacokinetic and pharmacodyamic research of Yiqing Capsule for anti-endotoxemiaAccording to preliminary results combined with TCM theory,this experiment had been chosen Yiqing Capsule,one of San-Huang preparations with comparative anti-endotoxin activity in vitro.With the index of the content of endotoxin in the serum and NO,peripheral hemodynamics,histomorphology and so on,Yiqing Capsule had been studied the pharmacodyamics of LPS-induced Beagle endotoxemia,the pharmacokinetics of treatment group and blank treatment group with baicalin and rhein as the index,and the determination of plasma concentration of baicalin and rhein which the pharmacokinetic parameters of had been analyzed by DAS.Treatment group and blank treatment group had been compared the pharmacokinetic parameters by T-test.On the basis of the pharmacodynamic experiments of anti-endotoxemia of Yiqing Capsule,the relevance of the pharmacodynamic and pharmacokinetic targets had been investigated with effective index of hemodynamics,the removal rate of anti-endotoxin and the inhibiting rate of NO.RESULTS1 San-Huang Formula anti-endotoxin activity in vitro and Chemical fingerprintsThe results showed that the chemical compositions of San-Huang preparations were of great difference with the main factors of baicalin,rhein and emodin that affected the quality of preparations.The chemical compositions,such as berberine,, baicalin,rhein,emodin,chrysophanol,and aloe-emodin,were correlated with anti-endo-toxin in vitro.2 the pharmaeokinetic and pharmacodyamic research of Yiqing Capsule for anti-endotoxemiaYiqing Capsule removed plasma endotoxin,inhibited the excessive release of NO, positively effected the peripheral hemodynamics parameters,apparently improved the pathologic change of histomorphology of LPS-induced Beagle endotoxemia,and also relieved the inflammation caused by endotoxemia.Contrasted the pharmacokinetic parameters between treatment group and blank treatment group,t_1/2ka,K_a and MRT(0-∞) of baicalin and C_max,T_max,T_1/2,K_a and K of rhein were of conspicuous disparity,and the velocity of resorption and metabolism of baicalin and Rhein of treatment group was notablely slower blank treatment group.Both of blood concentration-effect curve appeared significantly hysteresis loop that the peak of effect apparently lagged behind the peak of blood concentration,and the effect room was not in the blood room which appeared the phenomenon that the effect lagged behind the blood concentration.CONCLUSIONThrough the combination of in vitro and in vivo,the chemical fingerprints and effects,and pharmacokinetics and efficacy,San-Huang Formula was proved that could remove endotoxins and reduce the inflammatory caused by endotoxins,with the...