The absorption enhancement of norisoboldine in the duodenum of adjuvant-induced arthritis rats involves the impairment of P-glycoprotein.

Lindera aggregate (Sims) Kosterm root has been used in traditional Chinese medicine for the treatment of rheumatism palsy, dyspepsia and frequent urination for a long history. Norisoboldine (NOR), the main active constituent of this herb drug, possesses outstanding anti-arthritis activity. However, in vivo disposition of NOR has been known to a limited extent, especially under the pathological condition of rheumatoid arthritis (RA). The aim of this study is to investigate whether and how the absorption of NOR is altered in adjuvant-induced arthritis (AIA) rats. Comparative studies of the intestine absorption of NOR between normal and AIA rats at different pathological stages of the arthritis were performed by using in situ single-pass intestinal perfusion (SPIP), and the effects of the inhibitor of efflux proteins were also investigated. NOR was shown to be a substrate of P-glycoprotein (P-gp), as P-gp inhibitor verapamil (VER) markedly increased the permeability coefficient (Peff ) of NOR by 88% in intestine of normal rats. Compared with normal rats, AIA rats displayed increased Peff values of NOR by 84% and 86% on day 5 and d10 after the appearance of the secondary response of arthritis, respectively. VER could eliminate the difference of intestinal absorption of NOR between normal and AIA rats. Further studies showed that impaired expression and activity of P-gp in AIA rats play a decisive role in absorption enhancement of NOR. Notably, the impairment of P-gp function positively correlated with the severity of arthritis.

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