Primary Studies On The Metabolized In Vivo Rats’ Toxicity Of Rubia Cordifolia L.and The Pharmacokinetics Of Alizarin

Objective1.The blood components of Rubia cordifolia L. and the metabolic pathway of alizarin and purpurin were studied,which could provide a certain basis for the research on the effects of the Rubia cordifolia L.2.The pharmacokinetic study of Alizarin element was evaluated to get the behavior and regulation of alizarin in vivo.3.The toxicity of kidney,haper and the colon in rats were investigated after oral administration of Rubia cordifolia L.extract,which could provide a certain basis for dinical rational drug using.Methods1.An effective UPLC-Q-TOF/MS method was developed for analysing the chemical constituents in rat plasma after the oral administration of Rubia cordifolia L.extract.The study of chemical constituents in rat plasma was based on the study of the composition of Rubia cordifolia L.extract.The metabolic pathway of alizarin and purpurin was study after administration of Alizarin solution(0.63 mg/mL)and purpurin solution(3.25 mg/mL)were each prepared with 0.5%aqueous CMCC-Na.The Peak View Shortcut software and Metabolite Pilot TM 1.6 software were used for data analysis and processing.2.In SPF experimental conditions,6 SD male rats were lavaged by dosing madder extract(10 g/kg).After 20 min,40 min,80 min,100 min min,1 h,2 h,2.5 h,3 h,4 h,6 h,8 h,12 h and 24 h,in total of 13 time point in every rat blood samples were collected and the alizarin content of each rat plasma samples of different points will be determined in time for the Drug-time curve of alizarin.The pharmacokinetic software was employed for curve fitting,calculate the pharmacokinetic parameters.3.48 Wistar rats with half males and half females were randomly divided into control group,madder high dose,madder medium dose and low dose group(30,10,5 g/kg).The control group was given distilled water and these rat were continuous lavaged for 60 d.During the treatment,the general situation of rats(activities,mental state,diet,color luster,urine color)were observed and recorded.After the last oral administration of Rubia cordifolia L. extract,the blood biochemical indicators of animals,viscera coefficient and the change of pathological histology were observed.Results1.In the Rubia cordifolia L.plasma samples,11 prototype components and 17 metabolites were detected.Nine prototype composition and six metabolites of the 28 chemical compounds have been identified the structures..The metabolic pathway of alizarin and purpurin was mainly glucose aldehyde acidification and sulfating reaction on the alpha and beta a hydroxyl anthraquinone in addition reaction.In the hydroxyl madder element lavage drug-containing serum of rats,Rubia cordifolia L element and a hydroxyl madder isomers of compound content has been found,but the specific metabolic pathway is unclear.In addition,glucose aldehyde acid product of a hydroxyl madder can use an unknown metabolic pathways for addition reaction.In the Rubia cordi folia L.urine samples,8 prototype components and 6 metabolites were detected,and 5 prototype composition and 6 metabolitesof them were identified the structures.2.The pharmacokinetic characteristics of alizarin element was concordant with a two compartment model.The biological half-life of alizarin in rats was 3.9 h.3.The rat viscera index of each dose group was obviously increased(P<0.05).The level of Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)was increased significantly(P<0.01).The level of β2-MG and Cys-C in the male rat was also increased,but β2-MG in high dose group of female rat was significantly increased(P<0.01).Urea nitrogen(BUN)was no change(P>0.05).Liver and kidney tissues form was no obvious pathological changes.Colon tissue morphology,melanin staining and cell apoptosis in each dose group of Rubia cordifolia L.have no change compared with the control group.Conclusion1.The established method of fluid mass can be effective to the effective components in identification of madder.The main metabolic pathway of alizarin and purpurin could be the glucose aldehyde acidification and sulfating reaction.2.The pharmacokinetic characteristics of alizarin element was concordant with a two compartment model.The biological half-life of alizarin in rats was 3.90±0.47h.3.Rubia cordifolia L.had a mild toxic of liver and kidney when it’s dose has more than 5 g/kg.It can’t cause the rats colon melanosis.