Bioavailability Study of Glycyrrhetic Acid after Oral Administration of Glycyrrhizin in Rats; Relevance to the Intestinal Bacterial Hydrolysis

Abstract

To clarify the metabolic fate of glycyrrhizin when orally ingested, we investigated the bioavailability of glycyrrhetic acid, the aglycone of glycyrrhizin, after intravenous or oral administration of glycyrrhetic acid (5.7 mg kg-1, equimolar to glycyrrhizin) or glycyrrhizin (10 mg kg-1) at a therapeutic dose in rat. Plasma concentration of glycyrrhetic acid rapidly decreased after its intravenous administration, with AUC of 9200 +/- 1050 ng h mL-1 and MRT of 1.1 +/- 0.2 h. The AUC and MRT values after oral administration were 10600 +/- 1090 ng h mL-1 and 9.3 +/- 0.6 h, respectively. After oral administration of glycyrrhizin, the parent compound was not detectable in plasma at any time, but glycyrrhetic acid was detected at a considerable concentration with AUC of 11700 +/- 1580 ng h mL-1 and MRT of 19.9 +/- 1.3 h, while glycyrrhetic acid was not detected in plasma of germ-free rats at 12 h after oral administration of glycyrrhizin. The AUC value of glycyrrhetic acid after oral administration of glycyrrhizin was comparable with those after intravenous and oral administration of glycyrrhetic acid, indicating a complete biotransformation of glycyrrhizin to glycyrrhetic acid by intestinal bacteria and a complete absorption of the resulting glycyrrhetic acid from intestine. Plasma glycyrrhizin rapidly decreased and disappeared in 2 h after intravenous administration. AUC and MRT values were 2410 +/- 125 micrograms min mL-1 and 29.8 +/- 0.5 min, respectively. Plasma concentration of glycyrrhetic acid showed two peaks a small peak at 30 min and a large peak at 11.4 h, after intravenous administration of glycyrrhizin, with an AUC of 15400 +/- 2620 ng h L-1 and an MRT of 18.8 +/- 1.0 h. The plasma concentration profile of the latter large peak was similar to that of glycyrrhetic acid after oral administration of glycyrrhizin, which slowly appeared and declined. The difference of MRT values (19.9 and 9.3 h) for plasma glycyrrhetic acid after oral administration of glycyrrhizin and glycyrrhetic acid suggests the slow conversion of glycyrrhizin into glycyrrhetic acid in the intestine.

Saponins increase susceptibility of vancomycin-resistant enterococci to antibiotic compounds

“…The problems of oral treatment with glycyrrhizic acid are the low bioavailability caused by the poor absorption and the hydrolysis in the gastrointestinal tract [23,24]. In contrast to other saponins, glycyrrhizic acid, which is used in Japan for the intravenous treatment of chronic hepatitis [25], exerts a very low haemolytic activity (haemolysis index <2000) [14].…”

Recent Advancement of Chitosan-Based Nanoparticles for Oral Controlled Delivery of Insulin and Other Therapeutic Agents

“…Ammonium glycyrrhizinate is a salt of pharmacologically active glycyrrhetic acid, having potential anti-inflammatory, anti-tumorigenic and antihepatotoxic properties (64,65). However, the compound has poor oral absorption, which limits its clinical application and thus requires an effective delivery system (66).…”

Metabolism of Constituents in Huangqin-Tang, a Prescription in Traditional Chinese Medicine, by Human Intestinal Flora

“…[8][9][10][11][12][13][14] They were converted into the metabolites baicalein (B), paeonimetabolins (PM) and glycyrrhetinic acid (GA) by HIF in vitro, which were absorbed into body. [15][16][17][18][19][20][21][22][23] In our previous paper, 24) we established the method to simultaneously analyze the 14 chemical constituents of Huangqin-Tang by HPLC. Among these compounds, there are several pairs of original compounds and metabolites.…”