Changes in Intestinal Absorption Kinetics of Ginsenosides in Yi Gong San in the Rat Model of Spleen Deficiency and its Effect of Pericarpium Citri Reticulatae
Objective To investigate the effect of Pericarpium Citri Reticulatae on changes of the intestinal absorption of ginsenoside components in Yi Gong San based on the rat model of spleen deficiency and whether its effect is related to the exocytosis of P-gp protein.Methods The group design included the P-gp protein agonist rifampicin and the inhibitor verapamil,and 36 SD rats were randomly divided into a blank control group(6 rats)and a model group(30 rats),and then subcutaneously injected with rifampicin to establish a model of splenic deficiency,and then the model group was divided into the Yigong San fullparty(Y)group,the lack of Pericarpium Citri Reticulatae(Y-C)group,the YiGong San combined with rifampin(Y+R)group,the lack of Pericarpium Citri Reticulatae combined with verapamil(Y-C+V)group and the lack of Pericarpium Citri Reticulatae combined with rifampin(Y-C+R)group,Ginsenoside Rb1,ginsenoside Re and ginsenoside Rg1 were used as the index components in an in situ unidirectional intestinal perfusion test,and HPLC-MS was used to determine the content of the index components and to calculate the kinetic parameters of intestinal absorption,the effective permeability coefficient(Peff)and the absorption rate constant(Ka).Results Compared with group Y,Peff of ginsenoside Rb1 and Re were significantly lower in Y-C at multiple perfusion sessions,and Peff and Ka of ginsenoside Rb1,ginsenoside Re,and ginsenoside Rg1 were lower in Y+R at multiple perfusion sessions,suggesting that Pericarpium Citri Reticulatae promotes the intestinal absorption of ginsenoside Rb1 and ginsenoside Re and that this effect is related to the activity of the P-gp protein,but failed to change the intestinal absorption of ginsenoside Rg1.The P-gp protein inhibitor verapamil significantly increased the Peff of ginsenoside Rb1 and Re in the Y-C+V compared with the Y-C,while the P-gp protein agonist rifampicin significantly decreased the Peff and Ka of ginsenoside Rb1,ginsenoside Re,and ginsenoside Rg1 in the Y-C+R in multiple perfusion sessions.The significant decrease in Peff and Ka at multiple perfusion times suggests that ginsenoside Rb1,ginsenoside Re,and ginsenoside Rg1 may be substrates for P-gp proteins in the absence of Pericarpium Citri Reticulatae intervention.Conclusion Pericarpium Citri Reticulatae promotes the intestinal absorption of ginsenoside Rb1 and ginsenoside Re by exerting a verapamil-like effect that inhibits the activity of P-gp proteins in Yi Gong San.
Yi Gong SanKinetics of intestinal absorptionIn situ unidirectional intestinal perfusion testP-gp protein
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