| China was in ageing society and the needs for anti-aging medicine and anti-aging health care were urgent more and more.As far as concerned,the telomere hypothesis was a hypothesis more mature and influential for the mechanism of human aging.IIn a word,if we could activate telomerase in cells,the lengh of life would be prolonged.Recently,the biotech company Geron(US.)and nutraceutical companies had confirmed that the cycloastragenol had a significant role in telomerase activation.There were a series of studies about CAG have showed that CAG has significant anti-aging effect in mice.Main pharmacokinetic parameters of each group show that the t1/2 were similar.Cmax and AUC0?t were linearly correlated to doses.CAG was absorption by passive diffusion and widely metabolismed by rat or human liver microsomal.However,oral bioavailability and in vivo processes about CAG had not been reported.Therefore,we did reserch on pharmacokinetic,metabolism,and inhibitory effects of cycloastragenol on cytochrome CYP450 enzyme of rat liver microsomes of cycloastragenol and to provide basis research data for the explore and clinicl use.The paper includes the following four parts:Literature review It focused on the physicochemical properties testing means,pharmacological studies,in vivo processes as well as pre-treatment process detection of biological samples for testing of Astragaloside and cycloastragenol.Experienment The study showed that the oral bioavailability of CAG in rats was 17.4%,much higher than that of ATS;and there was enterohepatic circulation;and there was iso-CAG in rats and extraced through rat bile.Through the experiment about excretion pathway and excretion form of CAG,we suggested that CAG and iso-CAG was extracted by feces,and the most of the rest CAG was metabolised and then excreted.We applied glucuronidase hydrolysis and sulfatase enzyme to identify whether there were metabolites of cycloastragenol combined with glucuronidation and sulfuric acid or not in the fence.The result showed that there were no glucuronic and sulfuric acid conjugates bound form of substance excreted through feces,or its amount was very low.Rats were given cycloastragenol(40 mg·kg-1·d)for 7 days continuously to induce hepatic microsomal enzyme.Cocktail and liver microsome in vitro incubation method were adopted.The results showed that the activity of CPY2E1 was induced significantly,but the activity of CYP3A4 was inhibited significantly.There was no significant effect on CYP2D6,CPY2A1,and CPY2C9.The results showed the type of inhibition of CYP3A4 was sub-competitive inhibition.The expression of mRNA about CYP1A1,CYP2B1,CYP2C11,CYP2E1,CYP3A1 were determained by RT-PCR.The results showed that hepatic microsomal enzyme induced trend.Experiment Conclusion and DiscussionThis study aimed to study the vivo process of CAG to provide experimental evidence for formulation design of CAG;the bioavailability of CAG was higher,and it was expected to develop a new generation of anti-aging medicine;through research on inhibition of CAG playing on rat liver microsomal enzyme CYP3A4,we could provide experimental evidence for its future clinical applications,and minimize the occurrence of drug metabolism interactions. |
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