Comparative pharmacodynamic, pharmacokinetic and tissue distribution of Dahuang-Gancao decoction in normal and experimental constipation mice

Dahuang-Gancao decoction (DGD) is a classical formula, which is commonly used for reliving constipation in Chinese clinic. The aim of this study was to investigate the pharmacodynamic, pharmacokinetic and tissue distribution alternations of DGD in normal and constipation mice. DGD exhibited stronger purgative effect in constipation mice by the increased fecal excretion and reduced first defection time compared with normal mice. The C_max, AUC_0-t and MRT_0-t of rhein, aloe-emodin, rhein-8-O-β-D-glucoside, sennoside A, and glycyrrhizic acid as main bio-active components in DGD were markedly increased in constipation mice. The tissue distribution of the analytes in constipation mice were higher than those in normal mice with rhein > rhein-8-O-β-D-glucoside > aloe-emodin > glycyrrhizic acid > emodin in liver, and glycyrrhizic acid > rhein-8-O-β-D-glucoside > liquitin > sennoside A > rhein > aloe-emodin > emodin in colon. The kidney concentrations of the analytes showed a descending order of rhein > rhein-8-O-β-D-glucoside > sennoside A > glycyrrhizic acid > aloe-emodin > emodin, most of them were higher while rhein was lower in constipation mice than normal mice. The higher exposure of the anthraquinones in plasma, liver and colon may result in the stronger purgative effect in the constipation mice than normal mice. Rhein is mainly excreted through the kidney, the decreased level of rhein in constipation mice may explain the alleviated side effects. Accumulation of glycyrrhizic acid in colon may related with the moderate property of licorice. These results provided the experimental basis for understanding the therapeutic effects and metabolite profile of DGD.