Study On The Kinetics Of In Vivo Process Of Morroniside In Iridosides Of Cornus Officinalis In Rats And In Vitro Uptake Of Morroniside In Cells

Objectives: To study the concentration-time course, excretion and tissue distributionof morroniside in rats after single oral administration of iridosides of Comusofficinalis and uptake of morroniside in masangial cell and endothelial cell.Methods: 1 g/kg of iridosides of Cornus officinalis was administered to rats. Methanolwas used for deproteinization in samples. Concentration of morroniside in plasma,urine, feces, bile, and 15 tissues was measured by HPLC methods. In the experimentsof cell uptake, extra and intro distribution of morroniside was studied at the time pointof 120, 90, 60, 45, 30, 15, 10 and 5 min when 0.4 mg/mL morroniside was added andat the time point of 60 min when 1.6, 0.8, 0.4, 0.2, 0.1 and 0.05 mg/mL morronisidewas added.Results: The plasma concentration-time profile shows a double-peak phenomenon.Morroniside was essentially eliminated in 24 hours. The statistical moment methodwas used to calculate the pharmacokinetic parameters. C_max, T_max, T_1/2, MRT, AUC0-t,AUC0-∞and AUMC was 54.75±8.40μg/mL, 3 h, 0.46±0.37 h, 5.39±0.31 h,310.90±34.92μg·h/mL, 317.53±32.10μg·h/mL and 1708.80±167.41μg·h·h/mL,respectively. The accumulative excretion of morroniside in urine, feces and bile was7.57±0.67％in 24 hours, 26.03±1.25％in 24 hours and 2.06±0.13％in 12 hours,respectively. Morroniside distributed mostly in the gastrointestinal tract, and theconcentration was also high in the kidney. When 0.4 mg/ml morroniside was added,the extra and intro distribution of morroniside reached balance at the time point of 45min and 60 min in mesangial cell and endothelial cell, respectively, and sustainedthereafter. When different concentration of morroniside was added, the extra and introdistribution of morroniside reached balance at the concentration of 0.4 mg/ml and 0.2 mg/ml in mesangial cell and endothelial cell, respectively, and sustained thereafter.Conclusion: The pilot study suggests that enterohepatic circulation circle be the mainreason for the double-peak phenomenon. Morroniside was mainly excreted from thefeces, and was distributed mostly in the gastrointestinal tract and the kidney. Thetransport of morroniside through cells belongs to the "facilitated diffusion via carrier".Along with the result that the concentration of morroniside intro mesangial cell washigher than the endothelial cell, we postulated the there is "Morroniside TranspertCarrier" on the cell membrane. Furthermore, we postulate that this carrier is thematerial basis of Cornus officinalis "act on the kidney channel".