Abstract
Glycyrrhizae Radix is widely used as herbal medicine and is effective against inflammation, various cancers, and digestive disorders. We aimed to develop a sensitive and simultaneous analytical method for detecting glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin, the four marker components of Glycyrrhizae Radix extract (GRE), in rat plasma using liquid chromatography-tandem mass spectrometry and to apply this analytical method to pharmacokinetic studies. Retention times for glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin were 7.8 min, 4.1 min, 3.1 min, and 2.0 min, respectively, suggesting that the four analytes were well separated without any interfering peaks around the peak elution time. The lower limit of quantitation was 2 ng/mL for glycyrrhizin and 0.2 ng/mL for isoliquiritigenin, liquiritigenin, and liquiritin; the inter- and intra-day accuracy, precision, and stability were less than 15%. Plasma concentrations of glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin were quantified for 24 h after a single oral administration of 1 g/kg GRE to four rats. Among the four components, plasma concentration of glycyrrhizin was the highest and exhibited a long half-life (23.1 ± 15.5 h). Interestingly, plasma concentrations of isoliquiritigenin and liquiritigenin were restored to the initial concentration at 4–10 h after the GRE administration, as evidenced by liquiritin biotransformation into isoliquiritigenin and liquiritigenin, catalyzed by fecal lysate and gut wall enzymes. In conclusion, our analytical method developed for detecting glycyrrhizin, isoliquiritigenin, liquiritigenin, and liquiritin could be successfully applied to investigate their pharmacokinetic properties in rats and would be useful for conducting further studies on the efficacy, toxicity, and biopharmaceutics of GREs and their marker components.
Highlights
Glycyrrhizae Radix has been used as a herbal medicine because of a variety of pharmacological activities, including anti-oxidative, anti-cancer, and anti-diabetic activities as well as memory enhancing and inflammation reducing effects [1]
The results showed that that inter- and intra-day precision for glycyrrhizin, isoliquiritigenin, liquiritin, and liquiritigenin was inter- and intra-day precision for glycyrrhizin, isoliquiritigenin, liquiritin, and liquiritigenin was below below 13.6%
We investigated whether the biotransformation of isoliquiritigenin and liquiritigenin from liquiritin could occur in the rat intestine
Summary
Glycyrrhizae Radix (licorice root) has been used as a herbal medicine because of a variety of pharmacological activities, including anti-oxidative, anti-cancer, and anti-diabetic activities as well as memory enhancing and inflammation reducing effects [1]. It has been used as a flavoring agent in food products [2] and as an adjuvant to increase the therapeutic efficacy of other drugs. Radix and investigated the efficacy of Glycyrrhizae Radix extract (GRE) in relation to the modulation of reactive splenic T cells. For understanding the relationship between the response elicited by GRE and its pharmacokinetics, it was important to carry out the bioanalysis of the predominant or pharmacological components of GRE in biological samples following herbal extract administration and to understand their pharmacokinetics
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