Study On Intestinal Absorption Kinetics Of Salidroside And Its Metabolite P-tyrosol

Salidroside and its metabolite p-tyrosol are two natural phenolic secondary metabolites which widely exist in rootstalk of genus Rhodiola,possessing various pharmacological activities,can be used for the prevention and treatment of various diseases.In this thesis the rat intestinal perfusion model and Caco-2 cell model were developed to study the intestinal absorption kinetics of salidroside and its metabolite p-tyrosol.An UPLC-MS/MS method was established for the quantitative determination of salidroside and p-tyrosol(4-acetaminophen as the internal standard).The detection was performed in negative ion mode by multiple reaction monitoring(MRM).This method was simple,rapid,accurate,and could be successfully applied in the intestinal absorption kinetics studies of salidroside and its metabolite p-tyrosol.Using a rat intestinal perfusion model,the intestinal absorption of salidroside(5 ?g/mL)in various intestinal segments,and effects of P-gp inhibitor verapamil,MRP inhibitor indomethacin,paracellular enhancer EDTA in the intestinal absorption of salidroside were investigated.The intestinal absorption of p-tyrosol in various intestinal segments and intestinal absorption of p-tyrosol at different concentrations(2,5,10?g/mL)were explored as well.Results showed that no significant difference in the absorption of salidroside among various intestinal segments,salidroside had less intestinal absorption,and verapamil,indomethacin,EDTA could improve the intestinal absorption of salidroside.There was no significant difference in the absorption of p-tyrosol among various intestinal segments,p-tyrosol was absorbed well in intestine,and there was no significant difference in the absorption of p-tyrosol at different concentrations,suggesting the rat intestinal absorption of p-tyrosol without concentration dependency and mainly through the passive passway.Using a Caco-2 cell model,the bidirectional transport of salidroside(5 ?g/mL),and the effects of P-gp inhibitor verapamil,MRP inhibitor indomethacin,paracellular enhancer EDTA on the bidirectional transport of salidroside were investigated.the bidirectional transport of p-tyrosol at different concentrations(2,5,10?g/mL)were studied as well.Results showed that Papp value of salidroside was less than 1×10-6cm/s in AP?BL direction,further proving that salidroside is a difficult absorption compound.Verapamil and indomethacin increased the transport of salidroside in AP?BL direction,suggesting Verapamil and indomethacin improved intestinal absorption of salidroside,whereas EDTA could promote the bidirectional transport of salidroside.There was no significant difference among Papp value and efflux rate of p-tyrosol at different concentrations,suggesting the rat intestinal absorption of p-tyrosol without concentration dependency.Papp values of p-tyrosol at three concentrations were all larger than 10×10-6cm/s in AP?BL direction,which futher proved that p-tyrosol is an easy absorption drug.