Dose-response of oridonin on hepatic cytochromes P450 mRNA expression and activities in mice

Oridonin, the major terpene found in Rabdosia rubescens, is widely used as a dietary supplement or therapeutic drug. The effects of oridonin on drug processing genes, such as cytochrome P450 and nuclear receptors, were still unclear. Therefore, the present study investigated the influence of oridonin on the hepatic drug metabolizing system to evaluate the safety through its drug interaction potential.

In this study, eight-week-old male C57BL/6 mice were treated oridonin orally (0, 25, 50, 100, 200 mg/kg, i.g.) for 15 days. The effects of oridonin on major Cyps in mice livers were examined at both the mRNA and enzyme activity levels.

In general, there are no significant influence of various dose of oridonin on mice liver function. However, oridonin significantly increased Cyps (1a, 2a, 2d, 2e, 2c and 3a family) mRNA expression. In addition, it could induce Cyps activity in microsome incubation at maximum dosage. To our knowledge, it is the first time to identify oridonin as a Cyps inducer in vivo. It also promotes the expression of CAR, PXR and POR.

These results indicate that, if studies in mice extrapolate to humans by orthologous genes, oridonin appears to be a risk to herb-drug interactions due to its induction effects on drug processing genes expression and activation.