Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats.

The traditional Chinese medicines (TCMs) are essential components of alternative medicines. Many TCMs are known to alter the expression of hepatic drug-metabolizing enzymes and transporters. The molecular mechanism by which TCMs and/or their constituents regulate enzyme and transporter expression, however, has remained largely unknown. In this report, we show that two TCMs, Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch), and their selected constituents activate the xenobiotic orphan nuclear receptor pregnane X receptor (PXR). Treatment with TCM extracts and the Schisandrol and Schisandrin constituents of Wu Wei Zi induced the expression of drug-metabolizing enzymes and transporters in reporter gene assays and in primary hepatocyte cultures. The affected enzymes and transporters include CYP3A and 2C isozymes and the multidrug resistance-associated protein 2. In transient transfection and reporter gene assays, the Schisandrin constituents of Wu Wei Zi had an estimated EC50 of 2 and 1.25 microM on hPXR and mPXR, respectively. Interestingly, mutations that were intended to alter the pore of the ligand-binding cavity of PXR had species-specific effects on the activities of the individual Schisandrols and Schisandrins. In rats, the administration of Wu Wei Zi and Gan Cao increased the metabolism of the coadministered warfarin, reinforcing concerns involving the safe use of herbal medicines and other nutraceuticals to avoid PXR-mediated drug-drug interactions. Meanwhile, the activation of PXR and induction of detoxifying enzymes provide a molecular mechanism for the hepatoprotective effects of certain TCMs.

Stability of individual differences in cellular immune responses to two different laboratory tasks.

To explore the stability of immune reactivity across laboratory tasks, we correlated enumerative and functional lymphocyte responses to a speech task and a mental arithmetic task, delivered on the same occasion of testing in 31 healthy undergraduates. Both tasks were associated with an increase in peripheral CD8+ and CD56+ cell populations, and a decrease in proliferative response to phytohemagglutinin (PHA) and ratio of CD4:CD8 cells. Intertask correlations were significant for the magnitude of change in proliferative responses at two different concentrations of PHA, r = 0.76, p < .0001 and r = 0.46, p < .05, and in numbers of circulating CD56+ cells, r = 0.46, p < .005. Concomitant heart rate and systolic blood pressure responses also correlated significantly over the two experimental tasks (heart rate: r = 0.52 and systolic blood pressure: r = 0.58. ps < .0005). These data provide initial evidence that interindividual variability of some cellular immune responses is moderately reproducible across different stimulus conditions, providing further evidence that it may denote a stable individual difference.