Evaluation on hepatoprotection in Nrf2/ARE oxidation/chemical stress defense pathway caused by isoliquiritigenin based on analysis of bile acids / 中国药学杂志

ABSTRACT

OBJECTIVE: To evaluate hepatoprotection in Nrf2/ARE oxidation/chemical stress defense pathwaycaused by isoliquiritigenin (Iso) based on analysis of bile acids using profile of bile acids. METHODS: High performance liquid chromatography coupled with quadrupole mass spectrometry (HPLC-MS/MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and glycine conjugates. By the luciferase reporter gene assay for screening Nrf2-ARE signal targeting molecular experiments in liquorice extract, isoliquiritigenin was capable of markedly activating Nrf2-driven gene expression, therefore it was used to evaluate hepatoprotection in Nrf2/ARE oxidation/chemical stress defense pathway. RESULTS: Based on the analysis using principle components analysis (PCA), partial least square-discriminant analysis (PLS-DA), Nrf2+/+, Nrf2-/- and Iso Nrf2+/+ groups could be distinguished from their Iso Nrf2-/- group, which suggested that the variance of the contents of bile acids could evaluate hepatoprotection caused by Iso. Bile acids of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), cholic acid(CA), sodium taurodeoxycholate hydrate (TDCA), deoxycholic acid (DCA), taurocholic acid(TCA) proved to be important corresponds to Iso induced liver protection according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences among the four groups. It indicated that UDCA, CDCA, CA, TDCA, DCA and TCA could be considered as sensitive biomarkers of Iso induced liver protection. CONCLUSION: This work can provide the base for the further research on the evaluation and mechanism of hepatoprotection caused by liquorice.