Simultaneous Determination and Pharmacokinetic Characterization of Glycyrrhizin, Isoliquiritigenin, Liquiritigenin, and Liquiritin in Rat Plasma Following Oral Administration of Glycyrrhizae Radix Extract

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.

An effective UFLC–MS/MS method used to study pharmacokinetics of major constituents of Fukeqianjin formula in rat plasma

“…By comparing the pharmacokinetic characteristics of acortatarin A (3) and 9-epi-acortatarin A (4), although the half-life of both was close (t 1/2 was 2.66 and 2.20 h respectively), the AUC and C max of acortatarin A were much higher than 9-epi-acortatarin A which indicated the bioavailability of 9-epi-acortatarin A was lower than acortatarin A due to its relatively small exposure in the body. It can be seen that the structural characteristics of compounds itself influenced its absorption in vivo to a certain extent [ 19 ].…”

“…Reference compounds including 3,4,5-trimethoxyphenol-1-O-β-d-glucopyranoside (1), 5-hydroxypicolinic acid methyl ester (2), acortatarin A (3), 9-epi-acortatarin A (4) were isolated from Mahoniae Caulis [14], neoandrographolide (5), trans-ferulic acid (6), genistin (7), salicylic acid (8), jatrorrhizine (9), palmatine (11), andrographolide (12), berberine (13), 14-deoxy-11,12-didehydro-andrographolide (15), panicolin (16), andrograpanin (17), Z-ligustilide (18), and 7-O-methylwogonin (19) were isolated from the extracts of Fukeqianjin Formula as described in our previous report [7], ononin (10) and naringenin (14) were isolated from Spatholobi Caulis [15]. The internal standard (I.S.)…”

“…3 show that all the 19 compounds could be rapidly absorbed by the gastrointestinal tract after the extract of FKQJF were orally administered to rats at a single dose of 3.2 g/kg body weight, the concentration of which in plasma could be determined about 10 min later, and the plasma drug concentrations of most compounds reached the peak values at about 1-2 h. Two compounds, berberine (13) and andrograpanin (17), displayed peak times longer than 3 h (the T max were 8.00 ± 0.00 and 3.33 ± 2.31, respectively), indicating the gastrointestinal absorption of these two compounds was lower than that of other ones. The plasma concentrations of other compounds, 5-hydroxypicolinic acid methyl ester (2), acortatarin A (3), 9-epi-acortatarin A (4), jatrorrhizine (9), palmatine (11), naringenin (14) and 7-O-methylwogonin (19) decreased rapidly with the time prolongation after reaching peak values but could still be determined in plasma after a period. This result could be inferred that the absorption of this kind of compounds has the characteristics of fast absorption, fast elimination and long residence time.…”

The Calcium-Activated Chloride Channel TMEM16A is Inhibitied by Liquiritigenin

“…This flavonoid selectively activates an estrogen receptor β (Mersereau et al, 2008;Powell and Xu, 2008;Jiang et al, 2013). Liquiritigenin is maintained in the plasma over 24 h after oral administration of Glycyrrhizae radix extract (Han et al, 2019). Many pharmacological effects of liquiritigenin have been reported, such as anti-inflammatory effects, reduction of pain sensation, neuroprotection, and anti-cancer effects (Ramalingam et al, 2018).…”

Quantification of 10 bioactive components of Yazhangsan in rat plasma by LC–MS/MS and its application

“…Glycyrrhizae Radix et Rhizoma is often used to treat fever, pain, upper respiratory ailments, gastric ulcers and liver diseases (Wang, Pang, Cen, Zhu, & Xu, 2015). The main bioactive components of GR are saponins and flavonoids (Han, Kang, Yang, Choi, & Song, 2019). Glycyrrhizic acid and glycyrrhetinic acid are regarded as the two principal triterpenoids.…”