Study On Pharmacokinetics And Metabolites Of Ginsenosides After Oral Ginseng Decoction And Total Ginsenosides

Ginseng was widely used as a nutritious drug in clinic for their therapeutic effects on cardiovascular disorders,diabetes,nerve disease,inflammation,cancer etc.According to reports in literature,the main active components of ginseng were ginsenosides.Nevertheless,few investigations were available about metabolites and pharmacokinetics?PK?of total ginsenosides.Accordingly,to explore the PK behaviors and metabolites of ginsenosides after orally administered ginseng decoction?GD?and total ginsenosides?TG?,the six-year-old ginseng were boiled to get ginseng decoction,powders of TG were dissolved in water to get TG aqueous,which were both administered to mice and rats.The results of this study will set up theoretical and experimental basis for the new drug development of panax ginseng.1.Structural identification of metabolites of GD and TGUltra-performance liquid chromatograph tandem time-of-flight mass spectrometry?UPLC-Q/TOF-MS?combined with UNIFI data processing system was used to analyze the metabolites of ginsenosides after orally administered GD and TG.The results showed that most of the metabolites are propanaxadiol derivatives after oral GD,and the main metabolites are propanaxadiol combined 2 sugars;the metabolites of protopanaxtriol type were less than those of protopanaxdiol type,and commoly combined 1 or 2 sugar in the molecular structure.There was no significant difference of metabolic pathway between the two administrations.The only difference was that glycine-binding metabolites were detected after oral administration of GD,but not detected after oral administration of TG.2.Structural identification of metabolites of TG plus different proportions of polysaccharidesThe metabolites of ginsenosides after oral administration of different ratio of ginseng polysaccharides and TG were determined by the method of UPLC-Q/TOF-MS coupled with UNIFI software,which the ratios were 1:0.5,1:2,1:4respectively.Based on the results of the experiments,it was concluded that propanaxadiol type of ginsenoside metabolites and ocotillol metabolites increased with the ratio of ginsenosides to polysaccharides rising.There was no significant difference of metabolic pathway after oral administration of TG with different ratio of polysaccharides,indicating that ginseng polysaccharides had no significant effect on the original biotransformation of ginsenoside in vivo.3.The PK behaviors of ginsenoside Rb1,Rc,Rd after oral GD and TGPK behaviors of Rb₁,Rc and Rd after oral administration of GD and TG were studied.Compared the data of Rb₁ after oral administration of TG,the values of AUC and C_maxax were 3.2,and 3.7 times after oral administration of GD,explaining that the absorption of Rb₁ was enhanced,the bioavailability of Rb₁ was higher.The AUC and C_maxax of Rc after oral GD were less than oral administration of TG,but T_maxax did not change,suggesting that there was enhanced transformation of Rc after oral administration of GD compared of TG.In addition,T_1/2 of Rc after oral GD was much longer than TG,but MRT was not changed significantly.After oral administration of GD,the peak time of Rd reached 8 hours,Cmax and AUC were less than Rb₁ and Rc,and T_1/2 and MRT were the same as Rb₁.