Study On The Effects Of Water Extract Of Coreopsis Tinctoria Nutt.on Intestinal Microecology And The Intestinal Absorption And Pharmacokinetics Of Marein In Water Extract Of Coreopsis Tinctoria Nutt.

Objective:To study the effects of water extract of Coreopsis tinctoria Nutt.（WECT）on intestinal microecology of mice and the absorption and pharmacokinetic characteristics of marein in rats.Methods:With the content of marein and extract yield as evaluation indexes,the extraction conditions of the WECT were optimized by orthogonal experiment design.The morphological changes of gastrointestinal tract in mice after intragastric administration of WECT were observed by HE staining and scanning electron microscope.After the mice were given the WECT by gavage,the activities of amylase,cellulase and xylanase in intestinal tract of mice were determined by DNS colorimetry,and the protease activities were determined by Folin-phenol method.The number of Escherichia coli,Enterococcus,Lactobacillus,Bifidobacterium and bacteria in the feces of mice were determined by plate culture method.Intestinal absorption characteristics of marein in WECT were studied by isolated everted intestine model of rats.The intestinal flora of rats was co-incubated with marein under anaerobic conditions,and the effect of intestinal flora on the metabolism of marein in vitro was preliminarily studied by HPLC.Results:The extraction conditions were as follows:solid-liquid ratio of 1:70,extraction temperature of 80℃,10 min each time,extraction twice.There was no significant change in the mucosal morphology of gastrointestinal tract in mice after intragastric administration of water extract of WECT.For intestinal enzyme activity,compared with the blank group,the amylase activity of middle and high dose WECT group was significantly decreased（P<0.01）,the protease activity of each dose of WECT groups was significantly increased（P<0.01）,the cellulase activity of middle and high dose WECT groups was significantly increased（P<0.01）,and the xylanase activity of high dose WECT group was significantly increased（P<0.05）.Compared with the blank group,the number of bifidobacteria in the low dose group was significantly increased（P<0.01）,and the number of bacteria in the low dose WECT group was significantly decreased（P<0.01）;the number of Lactobacillus and Bifidobacterium in the middle dose WECT group was significantly higher than that in the blank group（P<0.01）,and the number of Enterococcus was significantly reduced（P<0.01）;the number of Escherichia coli and Enterococcus in the high dose WECT group was significantly lower（P<0.05）,and the number of Lactobacillus,Bifidobacterium and bacteria in the high dose WECT group was significantly higher than that in the blank group（P<0.01）.Under different drug concentration,marein was absorbed linearly in each intestinal segment.With the determination coefficient R²greater than 0.96,which was in line with the zero order absorption rate.With the increase of drug concentration,Ka also increased.The Ka of each intestinal segment was different,with the largest Ka value in the ileum,the second in the colon,and the smallest in the jejunum.The proportion of AUC_0→24hat low and middle doses was basically consistent with the increase of dose,and there was no significant difference in t_1/2β.However,the proportion of AUC_0→24hwas not increased after high dose administration,and t_1/2βwas significantly prolonged in the low and middle dose groups of high dose（P<0.01）.The characteristics of in vitro metabolic transformation of marein by intestinal flora were preliminarily studied by HPLC.By comparing the HPLC chromatogram,new substances with different polarity were detected,which was speculated to be the metabolites of marein.Conclusion:WECT has no irritation to gastrointestinal tract and has good biocompatibility.WECT can regulate intestinal enzyme activities and intestinal microorganisms,promote the proliferation of probiotics,inhibit the growth of scherichia coli and Enterococcus,and has a positive regulatory effect on intestinal microecology.At the same time,the intestinal microorganisms can affect the metabolism of marein,which is the main component of Coreopsis tinctoria Nutt.,indicating that Coreopsis tinctoria Nutt.has interaction with intestinal flora.Marein was mainly absorbed in ileum and colon,and its absorption mechanism was passive diffusion.In the high dose range,marein showed nonlinear kinetics in rats.