Study On Drug Metabolism Of Ursane-type Saponins From Radix Ilicis

Radix Ilicis Pubescentis, the root of Ilex pubescens Hook et Am, has long been a remedy in southern China for the faction of cooling the blood, activating blood circulation, invigorating pulse, anti-inflammatory and clearing away toxic materials. Modern pharmacological studies showed that it possessed actions as causing a strong and persistent dilation of the blood vessels, increasing the blood flow to the coronary artery, lowering blood pressure and reducing oxygen consumption of the cardiac muscles. According to reports of chemical constituents of the root of Ilex pubescens, its constituents were triterpenoid saponins, lignans, iridoids and fragrances, and the triterpenoid saponins were its main compounds. In the present study, the acute toxicity, metabolism in vitro and in vivo, pharmacokinetics of ursane-type saponins of Ilex pubescens Hook et Arn were invesitigated, for purpose to clarisy these ingredients’characteristics of absorption and metabolism, and to provide the basic information for the clinical application of Ilex pubescens Hook et Arn.The acute toxicities of ilexsaponin Ai and ilexgenin A were invesitigated. Experimental mice were administered the dose:ilexsaponin Ai, equivalent to clinical dose by 453 times; ilexgenin A, equivalent to clinical dose by 602 times. In the observed days, there has no mice was died, and the main organs were not anormal. The conclusion is that, the toxicities of ilexsaponin Ai and ilexgenin A are not obviously under the dose.The metabolism of ilexsaponin Ai in large and small intestinal fluids was investigated in vitro. Two metablites could be detected, one of the metablites was prototype (ilexsaponin Ai), and the other was its aglycone (ilexgenin A). The metabolism of ilexsaponin Bi in large intestinal fluids was analyzed in vitro, there were three compounds to be detected, and one of the metablites was prototype. Concerning the metabolism of ilexoside O, four ingredients were detected, and after 24h, the whole of ilexoside O was completely metabolited to the others metabolites. Through TLC results, we found the color of metabolites’spot was the same as prototype, we conjectured their mother nuclide was triterpenoid saponin. Thus we presume that the metabolic pathway of ursane-type saponins of Ilex pubescens Hook et Arn may be the degradation of the structure of sugar.After ig ilexsaponin A1 to mice for a long time, the metabolites in urine and feces were detected by TLC and HPLC. The results showed that ilexsaponin Ai and its aglycone were found in feces, but not in urine. The content of metabolites in feces was detected by HPLC. About 15.58%quantities were eliminated with the form of prototype, and 74.27% quantities were eliminated with the form of aglycone. The metabolites were separated and purified by silica gel columatography in the end. These results indicated that after ig ilexsaponin Ai, there may be a little of component was absorpted to blood, and the metabolic pathway of ilexsaponin Ai may be directly through the gastrointestinal tract and eliminated out of the body.After ig ilexsaponin Ai following single time, the metabolites in blood, gastric contents and small intestine contents were analyzed. The metabolites could not be detected in blood by HPLC; And in gastric contents, we could find ilexsaponin Ai after metabolited 3h, but aglycone and the other metabolites could not be found between the experiment process. In small intestine contents, ilexsaponin Ai could be detected after 3h, and its aglycone was found after 12h. The result showed that, after ig ilexsaponin Ai, there may be a little of ilexsaponin Ai was absorpted to blood and the small intestine may play an important role in metabolism.The pharmacokinetics of ilexsaponin Ai and ilexgenin A were investigated in rats after intravenous injection. And parameters of pharmacokinetics were calculated by DAS2.0 software. The both of blood plasma concentration-time course were fitted with 2-compartment model.According to the metabolism of Ilex pubescens Hook et Arn, we found that the toxicityies of ilexsaponin Ai and ilexgenin A were low. After ig saponins, they may be metabolited by gastrointestinal tract, and there could be a little of saponins was absorded to blood. In the end, the absorptions of ilexsaponin Ai and ilexgenin A were researched. The results showed that they were fitted with 2-compartment model.