Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats

Abstract

To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent Cmax (2377.57 ng/mL), Tmax (5 min) and AUC0-T (6625.54 mg/L*h), which was much higher than the Cmax (346.03 ng/mL), Tmax (2.00 h) and AUC0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG.

Formulation and Evaluation on Synergetic Anti-Hepatoma Effect of a Chemically Stable and Release-Controlled Nanoself-Assembly with Natural Monomers

“…Previous reports have shown that GA-specific receptors are expressed on hepatocytes (Stecanella et al 2021), which may be related to the fast accumulation of GA in the livers. However, it is not clear whether GA’s accumulation in other organs, including the lung 51 and the colon, 52 is associated with the GA-receptors. Whether the distribution of free TAN in various tissues is related to its physicochemical properties and receptors has not been reported so far, which needs to be further studied.…”

A Review of the Antiviral Activities of Glycyrrhizic Acid, Glycyrrhetinic Acid and Glycyrrhetinic Acid Monoglucuronide

“…Physiology-based pharmacokinetic studies indicated that GAMG can be absorbed quickly and effectively, and exert better pharmacological activities than GL. GAMG exhibited benign drug-like properties due to higher blood concentration and higher tissue distribution in the lungs and kidney [ 153 ]. GAMG can inhibit COVID-19 virus and remedy COVID-19 associated pneumonia.…”

Glycyrrhizae Radix et Rhizoma: The popular occurrence of herbal medicine applied in classical prescriptions

“…After entering the blood, glycyrrhizic acid undergoes hydroxylation or GluA (+GluA) and is catalysed by metabolic enzymes such as liver cytochrome P450 isoenzyme (cytochrome P450 isoenzyme, CYP450s) and UDP‐GluA transferase (UDP‐glucuronyl transferases, UGTs) to generate the corresponding metabolites (Koyama et al, 2017; W. Song et al, 2018). The main metabolites are glycyrrhetinic acid and 18β‐Glycyrrhetic acid 3‐O‐mono‐β‐ d ‐glucuronide (M. Cao et al, 2022). Moreover, Liquiritin can be deoxidized glucose (Glc) into liquiritigenin by digestive tract microorganisms, and then be absorbed into blood (S. Dong et al, 2014).…”