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Jiegeng Gancao decoction, which is composed of Jiegeng and Gancao at a weight ratio of 1:2, was widely used for treating pharyngalgia and cough for thousands of years. Our previous work indicated that Gancao could increase the systemic exposure of platycodin D and deapio-platycodin D, two main components in Jiegeng. However, whether Jiegeng could alter the pharmacokinetics of the main compounds in Gancao is still unknown. Thus, the purpose of this study was to compare the oral pharmacokinetics of flavonoids and saponins from Gancao alone vs. after co-administration with Jiegeng. Furthermore, Caco-2 cell transport and fecal hydrolysis were investigated to explain the altered pharmacokinetic properties. Pharmacokinetics results suggested that the bioavailability of liquiritin, isoliquiritin, glycyrrhizin and its metabolite, glycyrrhetinic acid, could be improved while bioavailability of liquiritigenin and isoliquiritigenin deteriorated when co-administered with Jiegeng. The Caco-2 transport study showed no significant difference of the Papp values of the main components in Jiegeng Gancao decoction when compared with those in Gancao decoction (p > 0.05). The in vitro metabolism study suggested that saponins and flavonoids glycosides in Gancao were influenced and the metabolic characteristics of most ingredients were consistent with pharmacokinetic results, such as liquiritin and glycyrrhetinic acid. The hydrolysis of liquiritigenin and glycyrrhizin observed with fecal lysate in vitro appeared consistent with the oral pharmacokinetics. Based on experiments, the pharmacokinetic profiles of six components in Gancao were influenced by Jiegeng. The metabolic process might partially contribute to the altered pharmacokinetic behavior. The metabolism of some components of Gancao appeared to be inhibited when coadministered with Jiegeng, possibly by the Jiegeng constituent platycodin.

Background: Platycodi radix, the dried root of Platycodon grandiflorum A. DC, has been widely used as food and herb medicine for treating cough, cold and other respiratory ailments, and platycodin D (PD) is one of the most important compounds in Platycodi Radix. Objective: The purpose of this study was to compare the pharmacokinetic characteristics, intestinal absorption and microbial metabolism of PD in monomer with that in Platycodi radix extract (PRE). Materials and Methods: In the pharmacokinetic study, the concentrations of PD in rat plasma were determined by ultra-performance liquid chromatography-tandem mass spectrometry and the main pharmacokinetic parameters were calculated by data analysis software (DAS). Besides, in vitro Caco-2 cells and fecal lysate were performed to investigate the intestinal absorption and metabolism, respectively. Results: The results from pharmacokinetics showed that the area under the curve, the peak concentration the time to reach peak concentration and mean residence time of PD in PRE were enhanced significantly compared with that in single PD. Caco-2 cells transport study indicated that the absorption of PD both in monomer and in PRE were poor owning that the permeability of PD were <1/106 cm/s. The hydrolysis degree of PD in PRE was significantly lower than that in monomer PD in fecal lysate, which might be illustrated by the other ingredients in PRE influenced the hydrolysis of PD via gut microbiota. Conclusion: These findings indicated that the difference of microbial metabolism, not apparent absorption in intestine for PD between in monomer and in PRE contributed to their pharmacokinetic difference. [ABSTRACT FROM AUTHOR]