| Rhizoma Coptis and Fructus Evodiae are commonly used in clinical medicine.There are many records in medical ancient books of past dynasties.The property of two drugs is cold and hot,respectively.With the different proportions of compatibility between Rhizoma Coptis and Fructus Evodiae,their clinical efficacy is different.This paper studies the intestinal absorption and absorption mechanism of quaternary alkaloids in Rhizoma Coptis after its compatibility from the perspective of absorption.In this paper,the everted intestinal sac model was used to analyze the intestinal absorption of Rhizoma Coptis and Fructus Evodiae in different intestinal segments with the compatibility ratio of Rhizoma Coptis and Fructus Evodiae was 1:1,2:1 and 6:1.The results showed that the average absorption amount and rate of berberine,palmatine and jatrorrhizine in each intestinal segment of Coptis and Evodia(2:1)were significantly higher than those of Coptis and Evodia(1:1,6:1).When the ratio of 2:1 is compatible,Fructus Evodiae can obviously promote the absorption of quaternary alkaloids in Rhizoma Coptis.The results of the absorption rate of different intestinal segments showed that the absorption rate of the three kinds of quaternary alkaloids in jejunum was the slowest,when the ratio of Rhizoma Coptis and Fructus Evodiae was 1:1,while the absorption rate of them in jejunum was the fastest when the ratio of Rhizoma Coptis and Fructus Evodiae was 2:1.When the ratio of Rhizoma Coptis and Fructus Evodiae was 6:1,the absorption rate of palmatine and jatrorrhizine was the fastest in jejunum,but the absorption rate of berberine was the fastest in ileum,and the second in jejunum.The results showed that the secretion amounts of three kinds of quaternary alkaloids from serosa surface to mucosal surface were higher than the absorption amounts from mucosal surface to serous surface,which indicated that the transport direction had a great influence on the absorption of quaternary alkaloids,due to the exocytosis effects of P-gp.In order to further reveal the absorption mechanism of Rhizoma Coptis and Fructus Evodiae compatibility,the everted intestinal sac model was used to analyze the influence of indole alkaloids(evodiamine and rutaecarpine)on the intestinal absorption of quaternary alkaloids.The results showed that the absorption of the three kinds of quaternary alkaloids has the time-dependent and concentration dependent phenomena,but it was not saturated at the current dose.The combination with evodiamine could obviously promote the absorption of berberine with high and low concentrations,and palmatine with low concentrations,and the amount and rate of absorption of quaternary alkaloids were increased,which indicated that evodiamine played a role of P-gp inhibitor to some extent.However,rutaecarpine had no significant effect on most parameters of berberine and palmatine,indicating that rutaecarpine had little effect on the absorption of berberine and palmatine.In order to more accurately explain whether the quaternary alkaloids could be as P-gp substrate,the effect of verapamil(a P-gp inhibitor)on the quaternary alkaloids was studied by using the everted intestinal sac model.To some extent,verapamil could affect the intestinal absorption of quaternary alkaloids,which could increase the absorption of palmatine and jatrorrhizine.Although the effect of verapamil on the absorption of berberine at the concentration in this experiment was not obvious,it could increase the absorption rate and permeability of high concentration berberine.The results indicated that quaternary alkaloids might be P-gp substrate.To sum up,different compatibility ratio,different intestinal segments and different transport direction have great influence on the absorption of the quaternary alkaloids in Rhizoma Coptis.The indole alkaloid(evodiamine)could play a role of P-gp inhibitor,it promoted the absorption of the quaternary alkaloids to some extent.The quaternary alkaloids could be P-gp substrate. |
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