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Absorption and biotransformation of four compounds in the Guizhi decoction in the gastrointestinal tracts of rats.

OBJECTIVE
To study the absorption and biotransformation of liquiritin, cinnamic acid, paeoniflorin, and glycyrrhizic acid in the Guizhi decoction (GZD) in the gastrointestinal tracts of rats.


METHODS
A simple and reliable high-performance liquid chromatography method was established and validated for the analysis of the four components of GZD simultaneously in the gastrointestinal tracts of rats. Rats were randomly divided into in situ gastrointestinal loop model, in vitro anaerobic culture model, and blank control groups. All rats were fasted for 12 h and anesthetized using 20% urethane. Subsequently, the abdominal cavity of each rat was opened, and the stomach, duodenum, jejunum, ileum, cecum, and colon were ligated. For the in situ gastrointestinal loop model group, 2.5 mL of GZD (1.0 g crude drug/mL, 37 ℃) were injected into the gastrointestinal tract. The abdominal incision was covered with warm, wet cotton, and animals were maintained at 25 ℃ . Then, we collected the gastrointestinal tract content after 1.5 h. For the in vitro anaerobic culture model group, the gastrointestinal tract contents of rats were collected and then cultured in 2.5 mL of GZD in an anaerobic environment at 25 ℃ for 24 h. For the blank control group, rats received the same volume of a normal saline solution instead of GZD. High performance liquid chromatography was used to detect the liquiritin, cinnamic acid, paeoniflorin, and glycyrrhizic acid concentrations in each group and calculate the absorption and biotransformation rates of each ingredient.


RESULTS
Cinnamic acid (low polarity) was more easily absorbed by each gastrointestinal part than the higher-polarity glycosides. However, the absorption rate in the cecum was higher than that in other parts. The four compounds, cinnamic acid, liquiritin, paeoniflorin, and glycyrrhizic acid, were transformed completely within 24 h in the cecum and colon, whereas they were hardly transformed in the stomach, excluding glycyrrhizic acid. In addition, all ingredients had higher biotransformation rates in the distal small intestine than that in the proximal small intestine.


CONCLUSION
Although a portion of the glycosides in GZD was directly absorbed as the prototype forms in the gastrointestinal tract, they were primarily metabolized and transformed into their corresponding metabolites by intestinal flora near the distal small intestine before their absorption.