Pharmacological Action And Pharmacokinetics Of Honghua Granule Against D-GlaN Induced Acute Liver Injury

Objective:To study the pharmacological effects of safflower granules on d-glan-induced acute liver injury in rats and the pharmacokinetic characteristics of safflower granules and hydroxysafflower yellow A in rats.Methods:（1）with the content and extract rate of hydroxysafflower yellow A as the comprehensive index,L₉（3⁴）orthogonal test was used to determine the best alcohol extraction method of safflower.（2）The single factor experiment was used to select the influencing factors,and the comprehensive scores of particle forming rate,moisture absorption rate and angle of repose were used.The L₉（3⁴）orthogonal experiment was used to determine the best forming process of safflower particles.（3）Wistar rats were randomly divided into normal group,model group,positive control group,high,medium and low dose group of safflower granules and lactose（adjuvant）group.The rats were administrated with stomach protecting liver tablet,safflower granules and lactose solution once a day for21 consecutive days.After the last administration,except the normal group and lactose group,the rats were administrated intraperitoneally with d-glan normal saline solution to create the liver injury model.Fasting for solids and not fasting for liguids 12 hours later,chloral hydrate was anesthetized,blood was taken,serum was separated by centrifugation at 3500r/min for 10min,frozen and stored,AST and ALT serum indexes were measured,some liver tissues from the same part of liver were fixed in 20%formaldehyde solution,and pathological changes were observed.（4）Wistar rats were randomly divided into two groups:Safflower granule group and hydroxysafflor yellow A group.Each group was divided into six groups.After administration,the rats Fasting for solids and not fasting for liguids 18 hours,and blood samples were collected in the vein plexus of 0.4ml in 1.5mlep tube at 0 h,0.25h,0.5h,0.75h,1H,1.5h,2h,3h,4h,5h,6h,respectively.After centrifugation for 10 minutes at 12000r/min,the upper plasma was drawn and placed in-20℃refrigerate.Analysis was performed at and analyze with high performance liquid phase.Results:（1）The best alcohol extraction technology of safflower:the ratio of material to liquid is 1:12,70%ethanol is used to extract twice,each time for 4h,concentrate the filtrate,freeze-drying,and get the extracts;（2）The best molding technology of safflower granules is the ratio of extract to auxiliary material is 2:1,adding75%ethanol 2.5ml to make the granules to form the best;（3）Safflower granules significantly reduce the activity of AST and ALT in serum of d-glan-induced acute liver injury rats In addition,the necrosis of hepatocytes was significantly reduced,and most of them returned to normal.Therefore,safflower granules significantly reduced the acute liver injury induced by d-glan;（4）The pharmacokinetic parameters of safflower granules and Hsya in rats were:Cmax was（2.12±0.52）ug/L and（2.32±0.41）ug/L,Tmax was（1.25±0.27）h and（1.17±0.26）h,AUC（0-t）was（4.67±0.48）ug/L,respectively/L*h and（4.78±0.42）ug/L*h,T_1/2 were(1.09±0.82h and（0.79±0.71）h respectively.Conclusion:（1）The best extraction conditions determined by the experiment provide the basis for the further study of ethanol extraction of effective components from safflower;（2）The formation process of safflower granules is simple and easy to operate,which lays the foundation for the research of safflower dosage form reform;（3）Safflower granules have certain anti acute liver injury effect;（4）According to the pharmacokinetic study and related index test results of Honghua granules,the highest content Cmax value of HSYA in the granules made of methanol extracted Honghua granules is higher than that of single HSYA,and Tmax value is also longer.Therefore,it can be known that the clinical effect is better after the granules are made,and the drug effect is stronger and longer.