Astragalus Armour Glycosides And Ring Astragalus Membranaceus Alcohol Metabolism In Vivo And In Vitro Studies

With the increasingly serious aging problem across the world,anti-aging and the researches of screening anti-aging medicine have become the main hot problem.At present,the influential aging mechanism is short-telomere theory. If activate telomerase,it can increase the number of cell division,then prolong lifespan.According to recent researches,CAG has significant telomerase activation.It has been reported that its parent structure AST has strong antioxidative activity.As fourth generation natural health and anti-aging drugs,they has caused wide public concern over the recent years.There are now several studies that have shown that saponins can happen carbohydrate hydrolysis in the body,and the metabolites including sapogenin as the main material into blood to play more important pharmacological effects.As the macromolecular saponins, AST has poor bioavailability,and its absorption,conversion or the real effect of composition etc in body are not clear. Physicochemical property of AST and CAG is different.It may lead to differences in bioavailability;affect absorption,distribution and metabolism;in turn further influence therapeutic effects.Thus,this topic centers on researching on the the process of metabolism,conversion parts and metabolites,after that to definite effective constituents.Firstly,study physicochemical properties of AST and CAG,then to discuss the metabolism properties in vivo and in vitro.Finally,clear metabolic pathways and provide experimental bases for promoting rational exploitation of health products.Three parts are included in this thesis:document study;experiment research;conclusion and discussion.Part1:Document study: developments in aging anti-aging drugs and health products research; Saponins pharmacokinetic study;overseas and domestic research status of AST and CAG.Part2:Experiment research:physicochemical property of AST and CAG; metabolism properties in vivo and in vitro.1Physicochemical property study of AST and CAGThe results of the approximate solubility and equilibrium solubility in water showed that AST and CAG are different in physical and chemical properties.2Metabolism of AST in vivo and in vitro(1) Metabolism of AST in vivoIn vivo samples including rat urine and feces samples were prepared individually after oral administration of40mg/kg AST to healthy rats,and metabolites of AST was identified by LC-MS/MS.There were2metabolites in rat urine:A(vivo)1(m/z513)and A(vivo)2(m/z543).M1 may be the sapogenin isomer.M2may be a methoxide metabolite for sapogenin.There were4metabolites in feces:A(vivo)1’(m/z513), A(vivo)2’(m/z513), A(vivo)3’(m/z543) and A(vivo)4’(m/z511). A(vivo)1’may be sapogenin-CAG; A(vivo)2’(m/z513) and A(vivo)3’(m/z543)was the same to rat urine. A(vivo)4’may be the dehydrogenation metabolite.(3) Metabolism study in vitroFirstly,study stability in the artificial gastric juice and in the artificial intestinal juice.The results showed that AST was stable during4h.By incubating AST with intestinal flora of rats and human,respectively,metabolites of AST in intestinal flora in vitro were detected.Results showed that AST was very easy to be hydrolyzed,produing CMG and sapogenin-CAG.In liver metabolism experiment,it was found that metabolism for AST rarely occurred.3Metabolism of C AG in vivo and in vitro(1) Metabolism of CAG in vivoIn vivo samples including rat urine and feces samples were prepared individually after oral administration of40mg/kg CAG to healthy rats,and metabolites of CAG was identified by LC-MS/MS.There were other7metabolites and CAG in rat urine:CAG(CO)and C1-C7, C1(m/z529),C2(m/z529),C3(m/z527),C4(m/z543),C5(m/z485),C6(m/z469) and C7(m/z353).There were CAG(C0’,C0-1’) and9other metabolites in feces:C1’(m/z527),C2’(m/z527),C3’(m/z529),C4’(m/z485),C5’(m/z499),C6’(m/z543),C7’(m/z455),C8’(m/z469) and C9’(m/z453).They may be oxidation and methylation metabolites.(2) Metabolism of CAG in vitroTo investigate the metabolickinetics of CAG in rat liver homogenate,by developing an in vitro system of rat liver homogenate, the factors including incubation time, homogenate protein concentration and original concentration of CAG were surveyed.The better original concentration was0.05mg-mL-1,better protein concentration was2.0mg·mL-1,better incubation time was40min.Vmax was6.88×10-5μmoL·(min-mg protein)-1.Km was18.8μmol·L-1。By comparing metabolism properties of CAG in different tissues, the research showed metabolic ability in heart,lungs,spleen and kidney is lower than in the liver.Part3:Conclusion and DiscussionAST was easily metabolized into sapogenin-CAG for its internal potency component.