Study On The Absorption Mechanism Of Active Ingredients In Traditional Chinese Medicine Corydalis Yanhusuo

In the process of absorption, distribution, metabolism and excretion of Chinese medicine active ingredients, absorption is the first step. Therefore, it is important to study the absorption characteristics of the active ingredients of the traditional Chinese medicine. At present, oral administration remains a dominant position in a variety of routes of administration. Small intestine is the main site of drug absorption.The object of this project is the active ingredients of Corydalis yanhusuo,such as tetrahydropalmatine, tetrahydroberberine, tetrahydrocoptisine and corydaline. The complexity and the integrity of the active ingredients of traditional Chinese medicine make the result of the mechanism of absorption and transportation of traditional Chinese medicine potency disappointing in the process of relying on a certain model. The intestine absorption mechanisms of the ingredients mentioned above were investigated using MDCK-MDR1cell model and in vivo intestinal perfusion model. The specific content as follow:In the first part of research, we study the absorption and transport mechanism of the active ingredients of Corydalis yanhusuo in the form of monomer, mixtures and medicinal extracts. In this part, Studying the absorption and transport mechanism of tetrahydropalmatine tetrahydrocoptisine and tetrahydroberberine monomer and discussed in detail the absorption characteristics of tetrahydropalmatine by using MDCK-MDRlcell model, the effect of P-glycoprotein, temperature and concentration on the absorption of tetrahydropalmatine. We come to conclusion that tetrahydropalmatine may be the substrate of P-glycoprotein by the P-glycoprotein inhibitor experiments. The absorption mechanism of tetrahydropalmatine may involve P-glycoprotein efflux. The experimental result of different temperatures and concentration also shows that the absorption mechanism of tetrahydropalmatine related to carrier-mediated active transport. Meanwhile, we also study the Tran membrane transport of tetrahydrocoptisine and tetrahydroberberine monomer by using MDCK-MDRlcell model. Experimental data show that the apparent permeability coefficient of tetrahydrocoptisine and tetrahydroberberine are greater than2.0×10-5cm/s. which shows that they are the high permeability. The efflux rate of tetrahydrocoptisine greater than2, indicating that the transmembrane transport of tetrahydrocoptisine may relate to carrier participation. While the absorption rate and efflux rate of tetrahydroberberine is almost the same, we can draw a conclusion that the absorption mechanism of tetrahydroberberine may be the passive transport. We also study the absorption properties of the mixture of tetrahydropalmatine tetrahydrocoptisine and tetrahydroberberine. The present of tetrahydrocoptisine and tetrahydroberberine is better to the absorption of tetrahydropalmatine, the efflux rate of tetrahydropalmatine and tetrahydroberberine in the form of mixture is greater than monomer, which indicates that the efflux rate is greater than the absorption rate in the form of mixture. In addition, we study the absorption and transportation of the extract of Corydalis yanhusuo, the result show that the apparent permeability of tetrahydropalmatine and tetrahydroberberine is smaller than that in the form of monomer, while the apparent permeability of tetrahydrocoptisine is not the case. The efflux rate of tetrahydropalmatine and tetrahydrocoptisine in the form of extract are greater than2, which showing that in the process of transmembrane transport, tetrahydropalmatine and tetrahydrocoptisine may be a carrier-mediated active transport.In the second part of the research,we study the intestinal absorption mechanism of corydaline,tetrahydroberberine and tetrahydropalmatine monomer, the three mixtures and Corydalis yanhusuo medicinal extracts in the intestinal perfusion model,the result of experiments show that corydaline, tetrahydroberberine and tetrahydropalmatine in the form of monomer, the three mixtures and Corydalis yanhusuo medicinal extracts all can be absorted by intestinal.but there have some differernce in the extent of absorption.the Ka of corydaline tetrahydroberberine and tetrahydropalmatine in the three mixtures were2.91×10-3min-1.2.94×10-3min-1and 3.91×10-3min-1respectively.which were greater than that in the form of monomer.which is due to the action of each other when they are mixted.which is better to absorpt for each other. the Papp of corydaline,tetrahydroberberine and tetrahydropalmatine in the form of Corydalis yanhusuo medicinal extracts were3.34×10-3cm/s.4.53×10-3cm/s and3.97×10-3cm/s respectively.compare to monomer. the Papp of corydaline in extracts is greater.while the Papp of tetrahydroberberine and tetrahydropalmatine is reduced.which indicated that the three ingredients in the extracts have some interaction in the process of absorption, tetrahydroberberine and tetrahydropalmatine is better to the absorption of corydaline. The absorption of tetrahydroberberine and tetrahydropalmatine in the form of extracts have bad effect on each other,or the alkaloi in the extracts also have a bad effect on these two ingredients.