| a-asaronol is the metabolites found in the early stage of the study group,based on the MS-linked technique,in the study of the "Liang Guanxi" of the "Juanzhi-Shichangpu"and the chemical "α-asarone".The study found that α-asaronol has a good antiepileptic activity and safety.The pharmacokinetic study was also carried out while trans-2,4,5 trimethoxy cinnamic acid was found and the content in the plasma was higher than that in the a-asaronol.In anti-epileptic activity studies,trans-2,4,5 trimethoxy cinnamic acid also has antiepileptic activity.Therefore,in order to further explore the main substances of antiepileptic activity,and previous studies on pharmacokinetics are confined to normal rats,this article is based on previous studies.the further metabolic research of a-asaronol and trans-2,4,5 trimethoxy cinnamic acid in normal rats and epilepsy rats was summarized as follows:1.Establishment of(HPLC-UV)method for the determination of a-asaronol and its major metabolite(trans-2,4,5 trimethoxy cinnamic acid)in normal rat plasma.The comparision between a and b pharmacokinetic study of normal rats and pentylenetetrazole(PTZ)induced epilepsy rats by intragastric administration of a-asaronol showed that:(1)(Intragastric administration)in normal rats and model rats in vivo metabolic process is different.The maximal plasma concentration(Cmax)of a-asaronol in the epilepsy model rats was higher than that in normal rats.The area under the curve of normal rats(AUC(0-t)),(AUC(0-∞)),mean residence time(MRT(0-t)),(MRT(0-∞))and elimination half-life(t1/2z)were higher than those in model rats,metabolic process is different between a and b suggesting that a-asaronol retention time in the blood is short.AUC(0-t),AUC(0-∞),MRT(0-t),MRT(0-∞)and ti/2z were significantly higher than those of normal metabolites(trans-2,4,5 trimethoxy cinnamic acid)in normal rats model rats.(2)a-asaronol(intravenous injection)in normal rats and model rats in vivo metabolic process is different between a and b.That AUC(0-t)and AUC(0-∞)were higher in normal rats than in normal rats,while that in MRT(0-t)and MRT(0-∞)And ti/2,were higher than model rats.trans-2,4,5 trimethoxy cinnamic acid in normal rats was higher than that of model rats with Cmax and AUC(0-t).The maximum plasma concentration(Cmax)of α-asaronol and its metabolites(trans-2,4,5 trimethoxy cinnamic acid)in the dose range of 25-100 mg · kg-1 is proportional to the area under the curve(AUC(0-t))which showed a linear trend with the increase of the dose,that is,α-asaronol and trans-2,4,5 trimethoxy cinnamic acid in nonnal rats and model rats suggest a linear metabolism.Because of the low bioavailability of α-asaronol in normal rats and model rats,oral administration is recommended.2.The(HPLC-UV)method of α-asaronol and trans-2,4,5 trimethoxy cinnamic acid in rat tissues was established,and the distribution of a-asaronol and trans-2,4,5 trimethoxy cinnamic acid in normal and model rats were studied.The results showed that:(1)a-asaronol was injected into the tail vein of normal rats for 5 min,and the concentration was:brain>heart>kidney>spleen>liver>lung;For 30 min is only in the spleen,liver,brain,and brain is highest;For 60 min and 90 min is none in all organization;The concentration in the model rats were injected with α-asaronol for 5 min is:brain>heart>spleen>kidney>liver>lung;For 30 min is:brain>liver>heart>spleen>kidney>lung;For 60 min is:spleen>kidney>heart>liver>Brain>lung;For 90 min is:kidney>spleen>heart>lung>liver>brain.(2)To the normal rat tail vein injection of a-asaronol,determination of α-capric acid content,For 5 min is:kidney>liver>lung>heart>spleen>brain;For 30 min is:kidney>lung>liver>spleen>heart>brain,For 60 min is:lung>kidney>liver>heart>spleen>brain,For 90 min is:kidney>heart>liver>lung>spleen>brain;The model rats were injected with α-asaronol intravenously to determine the content of trans-2,4,5 trimethoxy cinnamic acid;For 5 min is:lung>liver>heart>spleen>brain;For 30 min is:kidney>lung>liver>spleen>heart>brain,For 60 min is:lung>kidney>liver>heart>spleen>brain;For 90 min is:kidney>heart>liver>lung>spleen>brain;The trans-2,4,5 trimethoxy cinnamic acid was measured by intravenous injection of a-asaronol in model rats,For 5 min is:kidney>heart>liver>lung>spleen>brain;For 30 min is:kidney>heart>liver>spleen>brain;For 60 min is:kidney>heart>Liver>lung>spleen>brain,For 90 min is:kidney>spleen>heart>liver>lung>brain.α-asaronol and trans-2,4,5 trimethoxy cinnamic acid were distributed in all tissues.Among them,α-asaronol was mainly distributed in the brain,heart and spleen,and the content of trans-2,4,5 trimethoxy cinnamic acid was the highest in the kidney,and,the brain was the least.3.The method of(LC/MSD Trap)and(HPLC-UV)was established by the method of identification of a-asaronol in rats.A total of 8 compounds were identified,6 compounds of the blood samples and 8 compounds of the urine samples.Among them,blood samples,urine samples of metabolites:Sulfate a-asaronol,2,4,5 trimethoxy cinnamic acid glucuronate,hydroxyl 2,4,5 trimethoxy cinnamic acid glucuronate,cis-2,4,5 trimethoxy cinnamic acid,trans-2,4,5 trimethoxy cinnamic acid.Urine samples of the unique metabolites have 3 compounds:glucuronic acid hydroxyl a-asaronol ester and glucuronic acid a-asaronol ester and unknow;hydroxyl a-asaronol alone in the blood sample. |
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