HPXR activators

Baythrin hCEl, hCE2 Activated hPXR (> 3X), rPXR (> 3X) [29]... 

Other CYP3A4 inducers have also been reported to exert a pronounced effect on oral midazolam AUC (78), presumably through induction of intestinal and hepatic CYP3A4. For example, administration of phenytoin and carba-mazepine led to a 94% reduction in midazolam AUC compared with an untreated control population. Induction of CYP3A by St. John s wort, a widely used herbal supplement for the treatment of mild to moderate depression, has also attracted considerable interest. The major bioactive ingredient of St. John s wort, hyperforin, is a very potent in vitro activator of hPXR (79,80). Several groups have investigated induction of midazolam clearance by St. John s wort (81-83). As in the case of rifampin, clearance of oral midazolam... 

Alb-VP-hPXR Transgenic Mice Expressing the Activated hPXR... 

FABP-VP-hPXR transgenic mice were created to express the constitutively activated hPXR (VP-hPXR) in both the liver and intestine. Figure 1.5a shows the schematic representation of the transgene. Transgene expression was evaluated by Northern blot analysis using an hPXR-specific probe. As shown in Figure 1.5b, VP-hPXR was... 

The FABP-VP-hPXR mice were subsequently used to confirm that, like their Alb-VP-hPXR counterparts, activation of hPXR in this transgenic line also resulted in the disruption of adrenal steroid homeostasis [40] and promotion of hepatic steatosis [31]. 

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