RESUMO
Scutellarin is an important bioactive flavonoid extracted from Erigeron breviscapus (Vant.) Hand-Mazz, and scutellarein is the corresponding aglycone of scutellarin. The present study aims to compare the inhibition potential of scutellarin and scutellarein towards several important UDP-glucuronosyltransferase (UGT) isoforms, including UGT1A1, UGT1A6, UGT1A9 and UGT2B7. It was demonstrated that scutellarein exerted stronger inhibition towards the tested UGT isoforms than scutellarin. Furthermore, the inhibition kinetic type and parameters (Ki ) were determined for the scutellarein's inhibition towards these UGT isoforms. Competitive inhibition of scutellarein towards all these UGT isoforms was demonstrated, and the Ki values were calculated to be 0.02, 5.0, 5.8 and 35.9 µM for UGT1A1, 1A6, 1A9 and 2B7, respectively. Using in vivo maximum plasma concentration of scutellarein in rat, the in vitro-in vivo extrapolation was performed to predict in vivo situation, indicating the most possible in vivo adverse effects due to the inhibition of scutellarein towards UGT1A1. All these results remind us to monitor the utilization of scutellarin and scutellarein, and the herbs containing these two components.
Assuntos
Apigenina/farmacologia , Inibidores Enzimáticos/farmacologia , Glucuronatos/farmacologia , Glucuronosiltransferase/antagonistas & inibidores , Fígado/efeitos dos fármacos , Animais , Flavonoides , Isoenzimas/antagonistas & inibidores , Cinética , Fígado/enzimologia , Masculino , Ratos , UDP-Glucuronosiltransferase 1ARESUMO
Nanjing Ming city wall, one of the important historic heritages in China, has greatly suffered weathering. Microbes play an important role in the weathering of historic buildings. However, little is known about the microbial community inhabiting naturally weathered brick minerals and their roles in the mineral weathering. To examine the associations between microorganisms and brick weathering process, we compare the phylogenetic diversity, abundance, community structure, and specific functional groups of bacteria existing in weathered bricks by using a coupled approach involving cultivation-independent analysis of denaturing gradient gel electrophoresis (DGGE) as well as cultivation-based analysis of Si-releasing bacteria. DGGE and sequence analyses show that the bacterial communities were different along a weathering gradient and the abundance of bacterial communities positively and significantly correlates with the extent of brick weathering. Laboratory brick mineral dissolution experiments indicate that bacteria isolated from the surfaces of weathered brick were very effective in enhancing brick dissolution. Phylogenetic analyses show that the weathered bricks were inhabited by specific functional groups of bacteria (Bacillus, Massillia, Brevibacillus, Glacialice, Acinetobacter, Brachysporum, and Achromobacter) that contribute to the brick weathering.