Effect of Pericarpium Citri Reticulatae in Yigong San on MTL secretion and pharmacoki-netics of ginsenoside Rb1 in spleen deficiency syndrome rats and correlation analysis of PK-PD
Objective In order to explore whether Qi-promoting drugs promote the efficacy of tonics,this study analyzed the PK-PD correlation by comparing the difference of MTL secretion results and pharmacokinetic characteristics of ginsenoside Rb1 in spleen deficiency rats between Yigong San group and Yigong San without tangerine peel group.Methods The spleen deficiency syndrome rats were intragastrically administered with Yigong San(Y group),Yigong San without Pericarpium Citri Reticulatae(Y-C group),single Pericarpium Citri Reticulatae(C group)and normal saline(M group),and then blood was taken from jugu-lar vein at different time points.The plasma concentration of ginsenoside Rb1 was detected by liquid chromatography-mass spec-trometry,and the plasma concentration of MTL was detected by ELISA.The PK-PD model was fitted.Results The drug-time curves of the two groups showed double peaks,and there were two Cmax and two Tmax in the two groups.The peak concentration of Y group was significantly higher than that of Y-C group(P＜0.001),and the second absorption of Y-C group was signif-icantly higher than that of the first time(P＜0.01).At16h and 36h after intragastric administration,the content of MTL in plasma of rats in each administration group was significantly increased(P＞0.05),Y group＞Y-C group＞C group.The results of PD showed that the mean values of EC50 and γ in Y group were lower than those in Y-C group,and the mean value of Emax was higher than that in Y-C group,which was basically consistent with the fitting of PK-PD model.The fitting results of PK-PD model showed that the average values of Ka1,Ka2,AUC0-t,CL1,CL2,CL3,F,Tlag,EC50 and Emax in Y group were larger,and the values of Vd1,Vd2,γ and Ke0 in the Y-C group were larger.Conclusion The changes of blood concentra-tion of ginsenoside Rb1 and MTL in spleen deficiency syndrome rats have a certain correlation with the the content of Pericarpium Citri Reticulatae in Yigong San.One of the mechanisms of Pericarpium Citri Reticulatae in Yigong San to enhance the tonic effect may be to promote the absorption and absorption rate of ginsenoside Rb1 in Yigong San,and the distribution is more concentrated in the effect site,so that the affinity between ginsenoside Rb1 and MTL may be stronger,resulting in the increase of MTL secre-tion,promoting gastrointestinal movement.
Yigong SanPericarpium Citri ReticulataeSpleen Deficiency SyndromeGinsenoside Rb1MTLPhar-macokineticsPharmacodynamicsPK-PD model
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