Simultaneously screening multiple UGT1A1 inhibitors from Polygonum multiflorum root using ultrafiltration liquid chromatography-mass spectrometry

This study was deliberately designed to simultaneously screen the UGT1A1 inhibitors from PMR and their co-contribution to the hepatotoxicity was evaluated. With ultrafiltration coupled to liquid chromatography-mass spectrometry method, four compounds namely cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside, trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, emodin-8-O-β-D-glucoside and emodin were screened out, displaying the in vitro inhibitory activities against UGT1A1 with IC50 values of 76.23, 18.70, 62.18, 34.02 μM, respectively. The varying activities of screened UGT1A1 inhibitors were explained by performing a molecular docking simulation. Finally, zebrafish larvae and mice assays demonstrated that the UGT1A1 inhibitors co-contributed to the hepatotoxicity of PMR. Hopefully, these findings are conducive to understand the acting role of UGT1A1 inhibitors in PMR-induced hepatotoxicity.PMID:34921409 | DOI:10.1002/bmc.5300
Source: Biomedical Chromatography : BMC - Category: Biomedical Science Authors: Source Type: research