Effects of Glycyrrhizic Acid on Solubility,Pharmacokinetics and Liver Distribution of Osthole in Rats
10.14148/j.issn.1672-0482.2023.1076
- VernacularTitle:甘草酸对蛇床子素溶解度及其在大鼠体内的药代动力学和肝脏分布的影响研究
- Author:
Fei YUN
1
;
An KANG
;
Jin-Jun SHAN
;
Xiao-Li ZHAO
;
Xiao-Lin BI
;
Liu-Qing DI
Author Information
1. 江苏联合职业技术学院常州卫生分院,江苏 常州 213002;南京中医药大学药学院,江苏 南京 210023
- Keywords:
osthole;
glycyrrhizic acid;
glycyrrhetinic acid;
solubility;
pharmacokinetics
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2023;39(11):1076-1085
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the potential of glycyrrhizic acid(GL)to improve the solubility and bioavailability of ost-hole(Ost),and to explore the underlying mechanism of the potential solubility and pharmacokinetic interactions.METHODS Male Sprague-Dawley rats were orally given osthole(20 mg·kg-1)alone or with glycyrrhizic acid(45 mg·kg-1).Blood and liver samples were collected at specific time points and determined by an LC-MS/MS method.The effect of glycyrrhizic acid on the solubility of ost-hole,and physical characterizations,including X-ray diffraction(XRD)and Fourier transform infrared(FT-IR)spectroscopy,were performed to reveal the mechanism of the solubilization of GL.In addition,bidirectional transport study using Caco-2 cell monolayer model was employed to study the effects of glycyrrhizic acid and its active metabolite glycyrrhetinic acid(GC)on the absorption of ost-hole.In incubation studies,rat enterocyte S9 and liver S9 were used to explore the potential effect of GL and GC on the metabolism of osthole.RESULTS The results of pharmacokinetics in rats showed that co-administration of glycyrrhizic acid could significantly in-crease the AUC of osthole as compared with osthole administered alone.The results of rat liver tissue samples indicated that glycyrrhizic acid increased the distribution of osthol in liver tissue.Solubility study found that glycyrrhizic acid could significantly enhance the solu-bility of osthole in water due to the decreased crystallinity of osthole and the formation of hydrogen bonding between Ost and GL.Caco-2 cell monolayer model demonstrated that neither GL nor GC could enhance osthole absorption.Further in vitro incubation study re-vealed that there was little metabolic interaction between osthole and GL or GC in phaseⅠmetabolism.CONCLUSION Increased AUC and liver concentration of osthole are probably due to the increased solubility of osthole by GL.The current study has significant implications for further investigation on the potential combination use of natural solubilizing agent GL and drugs with solubility as the rate-limiting step to absorption from the gastrointestinal tract.
