The intestinal absorption of triptolide for the treatment of rheumatoid arthritis is mediated by transporters.

Tripterygium wilfordii Hook. f. is a traditional Chinese herb that is used to treat rheumatoid arthritis (RA). Triptolide (TP), an epoxidized diterpene lactone extracted from this herb, has been suggested to be the primary active and toxic component. In this work, the material basis and molecular mechanism of toxicity induced by T. wilfordii preparations in RA were investigated. Female rats with collagen-induced arthritis were given 500 μg·kg TP intragastrically or intravenously. Compared with that in the control group, the AUC in the CIA group was 1.7-fold greater after intragastric administration, while this value decreased 22.6 % after intravenous administration, suggesting that the absorption of TP was significantly greater in the CIA group. The results from RT-PCR and probe substrate perfusion indicated that Oatp1a5 expression was upregulated while P-glycoprotein (P-gp) expression was downregulated in the duodenums of CIA rats. Naringin, an inhibitor of Oatp1a5, decreased the P of TP in the rat duodenum by 27.9 %, whereas verapamil hydrochloride, an inhibitor of P-gp, increased the P by 50.8 %, suggesting that Oatp1a5 and P-gp mediate the uptake and efflux of TP in the rat duodenum, respectively. Furthermore, among the upstream nuclear receptors, the mRNA expression levels and protein expression levels of FXR and VDR were noticeably decreased. In the present study, the absorption of TP in the duodenums of CIA rats significantly increased due to the upregulation of Oatp1a5 expression and the downregulation of P-gp expression, leading to an increase in TP plasma exposure after intragastric administration. The altered expression of Oatp1a5 and P-gp may be related to FXR and VDR.