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 Cmax, AUC0-t and MRT0-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.