Research On Intestinal Absorption Mechanism Of Rhubarb Anthraquinone Through Intestinal Perfusion

Object:Investigate the intestinal absorption of rhein emodin and aloe-emodin in the rats. Discover how P-glycoprotein (P-gp) and Multidrug resistance-associated protein (MRP) which in the Intestinal epithelial cells affect intestinal absorption of rhein emodin and aloe-emodin.Methods:(1) Separately determination the concentration of aloe-emodin rhein and emodin in the samples of perfusate by reversed phase high performance liquid methods.(2) Using the single pass intestinal perfusion (SPIP) technique on Sprague/Dawley rats. SPIP was performed on each isolated region of the intestine (i.e. duodenum, jejunum, ileum and colon). According to the concentration-change of aloe-emodin rhein and emodin, calculate their effective intestinal absorption rate constant (Ka) and apparent absorption coefficient (Papp).(3) According to the value change of Ka and Papp after adding different concentrations of hydrochloric acid Verapamil (inhibitor of P-gp) and the indomethacin (inhibitor of MRP2), study the effectiveness of P-gp and MRP2 on aloe-emodin rhein and emodin intestinal absorption.Results:(1) In duodenum, aloe-emodin exhibits high intestinal permeability compared with which in the ileum(P<0.05), but there is no signifcant differences between others intestine regions (P>0.05); Addition to the inhitor of P-gp, the value of Ka and Papp has signifcantly increased compared with the normal group(P<0.01); The highest concentration and the medium concentration inhibitor groups of MRP2 have significantly increased compared with the group without inhibitor of MRP2(P<0.05).(2) The result is that the value of Ka and Papp have no signifcant differences between different sections (P>0.05); After addiding the inhitor of P-gp and MRP2, the value of Ka and Papp have no signifcant change compared with the group without inhibitor (P>0.05).(3) The main absorption position of emodin is in duodenum, Ka and Papp are signifcantly heigher than in other intestinal sections (P<0.05), the absorption of emodin in other intestinal sections have no signifcant difference (P>0.05). Compared with group without inhibitor, affter adding the highest concentration and the medium concentration of MRP2, the value of Ka and Papp have signifcantly increased (P<0.01). Adding the inhibitor of P-gp, the intestinal absorption of emodin have no signifcantly change (P>0.05).Conclusion:The aloe-emodin are well absorbed, the mainly absorption position is in the duodenum, but it is weak absorbed in ileum. Based on these results, suggests that the inhibitor of both P-gp and MRP2 can promote the intestinal absorption of aloe-emodin. The rhein is easily absorbed in all intestinal sections. After adding the inhibitor of P-gp and MRP2, there have no signifcant influence on the intestinal absorption of rhein. The P-gp and MRP2 may not efflux the rhein. The emodin is well absorbed, the main absorption position is in duodenum. Based on the results, P-gp cannot efflux the emodin, but the MRP2 can pormote the intestinal absorption of emodin. So emodin may be the substration of MRP2.