Pharmacokinetics and tissue distribution of 12 major active components in normal and chronic gastritis rats after oral administration of Weikangling capsules

Abstract

Ethnopharmacological relevance: Weikangling Capsules (WKLCs) have been used in the clinic for the treatment of gastrointestinal disorders for more than 30 years. However, the pharmacokinetic characteristics and tissue distribution of its major bioactive components in rats under different physiological and pathological conditions are unclear.

Aim of the study: In this study, we aimed to clarify the differences in pharmacokinetic parameters and tissue distribution of the major active components in WKLCs under physiological and pathological states.

Materials and method: Normal and ethanol-induced chronic gastritis rats received 2.16 g/kg WKLCs by gavage, and urine, feces, plasma, and tissue (heart, liver, spleen, lung, kidney, stomach, and small intestine) samples were obtained. The active components in urine, feces and plasma were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). A rapid and sensitive analytical method, ultra-high-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-QTRAP-MS/MS), was established and validated to clarify and compare the pharmacokinetics and tissue distribution of the major active components in normal and chronic gastritis rats.

Results: A total of 36 chemical components in the feces, urine, and plasma of chronic gastritis rats were identified by UHPLC-Q-TOF-MS/MS. Among them, 20 were the prototype components of WKLCs, and 16 were metabolites. The pharmacokinetic characteristics and tissue distribution of 12 prototype components were successfully analyzed by UHPLC-QTRAP-MS/MS. The pharmacokinetic results showed that the C_max, AUC_0-t, and AUC_0-∞ of paeoniflorin, glycyrrhizic acid, and glycyrrhetinic acid were distinctly higher than those of the other components in normal and chronic gastritis rats. Compared to normal rats, the C_max, AUC_0-t, and AUC_0-∞ of albiflorin, liquiritin apioside, liquiritin, isoliquiritin, ononin, isoliquiritigenin, dactylorhin A, and glycyrrhizic acid were significantly increased in chronic gastritis rats (P < 0.05), while the C_max, AUC_0-t and AUC_0-∞ of militarine and liquiritigenin had significantly lower decreases in chronic gastritis rats (P < 0.05). The results of the tissue distribution showed that the 12 components were widely distributed in the heart, liver, spleen, lung, kidney, stomach, and small intestine of rats, of which the liver, kidney, stomach, and small intestine were the main accumulative organs. Compared with normal rats, the concentrations of 12 components in the liver, kidney, stomach, and small intestine of chronic gastritis rats were widely higher than those of normal rats at the same time points.

Conclusion: The pharmacokinetic characteristics and tissue distribution of 12 active components of WKLCs were comprehensively characterized and elucidated in normal and chronic gastritis rats. These findings laid a solid foundation for revealing the pharmacodynamic material basis of WKLCs in treating gastrointestinal disorders.

Keywords: Active components; Chronic gastritis; Pharmacokinetics; Tissue distribution; Weikangling capsules.