Ginseng, a traditional herbal medicine, may interact with several co-administered drugs in clinical settings, and ginsenosides, the major active components of ginseng, may be responsible for these ginseng-drug interactions (GDIs). Results from previous studies on ginsenosides' effects on human drug-metabolizing P450 enzymes are inconsistent and confusing. Herein, we first evaluated the inhibitory effects of fifteen ginsenosides and sapogenins on human CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 enzymes by using commercially available fluorescent probes. The structure-activity relationship of their effects on the P450s was also explored and a pharmacophore model was established for CYP3A4. Moreover, substrate-dependent phenomena were found in ginsenosides' effects on CYP3A4 when another fluorescent probe was used, and were further confirmed in tests with conventional drug probes and human liver microsomes. These substrate-dependent effects of the ginsenosides may provide an explanation for the inconsistent results obtained in previous GDI reports.
SummaryVibrio cholerae live in aquatic environments and cause cholera disease. Like many other bacteria, V. cholerae use quorum-sensing (QS) systems to control various cellular functions, such as pathogenesis and biofilm formation. However, some V. cholerae strains are naturally QSdefective, including defective mutations in the quorum sensing master regulator HapR. Here we examined the QS functionality of 602 V. cholerae clinical and environmental strains isolated in China from 1960-2007, by measuring QS-regulated gene expression. We found that a greater percentage of the toxigenic strains (ctxAB + ) had functional QS as compared to the non-toxigenic strains (ctxAB − ), and that this trend increased significantly over time. We hypothesize that QS provides adaptive value in V. cholerae pathogenic settings.
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