| Bacopa monnieri, which belongs to the creeping herb Bacopa monnieri(L.) Wettst. of the scrophulariaceae.And the whole plant can antipyretic detoxicate and improving acuity of vision.And also,Whole plant used as the medicine, has the swelling effect.Modern studies have shown that BM total saponin is the effective parts of Bacopa monnieri, and BacopasideⅠis the main active ingredient.However, the findings by the research group Zhang Weidong College of Pharmacy,Second Military Medical university, shown that BacopasideⅠhas a low bioavailability which is only 0.1%. It is necessary to study the possible metabolic pathways and the site of metabolism of the BacopasideⅠ after the Oral Drug Administration in vivo, and the major metabolite of BacopasideⅠafter the BacopasideⅠwas brooded in the different biological matrices,such as Liver microsomes, plasma, kidney homogenized intestinal homogenate, mesenteric homogenized intestinal bacteria.In order to find the site and the characteristics of the metabolism and the metabolic stability of BacopasideⅠ.To Provide guidance for the development of new drugs and rational drug preclinical.Macroporous resin was used to get the crude methods of the Bacopa monnieri,which is the effective parts of Bacopa monnieri named Bacopa saponins. And the HPLC-MSn was used to identify the main ingredient of the Bacopa saponins.The Bacopaside I and Bacopaside II was prepared by the High performance Liquid Chromatography(HPLC),which purity is 90%. And, the finger prints of 15 batches of Bacopa saponins was established by the High performance Liquid Chromatography-Diode Array Detector(HPLC-DAD) and High performance Liquid Chromatography-Corona Charged aerosol Detector(HPLC-CAD).And also the two fingerprints are compared with each other. To evaluate the metabolic stability of the candidate compounds BacopasideⅠis the key to its early drug discovery.When we study the metabolites and the metabolic stability of BacopasideⅠin the different parts of body,vitro metabolism in Liver microsomes, plasma, kidney homogenized intestinal homogenate, and mesenteric homogenized intestinal bacteria was researched to find the metabolism site of the BacopasideⅠ.And the study is focus on the metabolites and metabolic in liver microsomes from four kinds of animal which is used in laboratory usually.To study the species differences between liver microsomes from four kinds of animals.The result: The fingerprints of 15 batches of Bacopa saponins were established by the HPLC-DAD and HOLC-CAD.Through the experiment,which is studying the metabolic site of the BacopasideⅠ,found that the main reason why BacopasideⅠhas a low oral bioavailability, because the drug metabolized maybe in the bacteria of the intestine and mesentery. The study of the metabolism of BacopasideⅠin the liver microsomes found that the reaction system of the BacopasideⅠbrooded in liver microsomes incubation occurs mainly to the hydroxymethyl, reduction of the double bond, a sulfionic acid group off, eliminate hydroxyl and off the five-carbon sugar reaction. And in different species(SD rats, Beagle dogs, monkeys and hμmans) liver microsomes brooded incubation systems are basically the same major metabolite.BacopasideⅠ in four different species of liver microsomes metabolism Tl/2(min),CLint(m L·min-1·Kg-1) and CLh(m L·min-1·Kg-1) ranges are 165.00min~277.2min,3.71 m L·min-1·Kg-1~10.47 m L·min-1· Kg-1, 3.42 m L · min-1 · Kg-1 ~ 7.82 m L · min-1 · Kg-1.Metabolism in vivo studies show, less polar triterpenoids was mainly formed in vivo metabolis of Bacopa saponins. After tail vein injection by BacopasideⅠ,sulfonic acid groups, alcoholic hydroxyl, furanose, the alcoholic hydroxyl group and continue to de-methylated metabolites after sugar were mainly generated in the body. |
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