Effect of sinomenine on the in vitro intestinal epithelial transport of selected compounds.

ABSTRACT

Herbal products can interfere with allopathic medicinal treatment through pharmacokinetic and pharmacodynamic interactions. Although pharmacokinetic interactions that alter drug absorption may cause variable and unsatisfactory drug bioavailability, a drug absorption enhancement effect of a herb may be used to ensure sufficient absorption of poorly absorbable drugs. The effect of the hydrochloride salt of sinomenine, an alkaloid obtained from the plant Sinomenium acutum, on the transepithelial electrical resistance and transport of different compounds (including cimetidine, vitamin C, rutin, luteolin and insulin) across Caco-2 epithelial cell monolayers was investigated in this study. Sinomenine HCl induced a concentration dependent lowering effect on the transepithelial electrical resistance of Caco-2 cell monolayers, which was completely reversible. Sinomenine HCl significantly increased the transport of all the test compounds in the apical-to-basolateral direction compared with the control group and decreased the transport of cimetidine, a P-glycoprotein substrate, in the basolateral-to-apical direction. From these results it can be concluded that sinomenine HCl increases drug absorption across the intestinal epithelium by means of one or more mechanisms including a transient opening of the tight junctions (as indicated by a reduction in transepithelial electrical resistance) to allow for paracellular transport and/or inhibition of active drug efflux transport (as indicated by inhibition of basolateral-to-apical transport of cimetidine).