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There is growing concern that co-administered herbal medicines may alter the pharmacokinetics and, therefore, the efficacy and toxicity of Western drugs. The aim of this study was to investigate the potential membrane permeation modulating effects of four herbal extracts, i.e., Harpagophytum procumbens, Hoodia gordonii, Leonotis leonurus, and Vitis vinifera on a model compound, Rhodamine 123 (RH-123). Methods: An in vitro permeation model, i.e., excised pig intestinal tissue, mounted to test chambers in a Sweetana-Grass diffusion apparatus, was used to measure the bi-directional transport of RH-123 in the presence and in the absence of four herbal extracts. The concentration of transported RH-123 in each sample was determined by means of fluorescence spectroscopic analysis. The integrity of the mounted jejunum tissue during experimentation was confirmed by measuring the permeation of Lucifer Yellow through these membranes. Trans-epithelial electrical resistance (TEER) of the mounted membranes was also measured at the onset and termination of each experiment to monitor whether tight junction modulation occurred. Results: H. procumbens extract increased the secretory transport of RH-123, indicative of the induction of P-glycoprotein (P-gp) mediated efflux. H. gordonii extract also increased RH-123’s absorptive transport, coupled with a subsequent decrease in its secretory transport, indicating the P-gp related efflux inhibition. Contrary, L. leonurus extract reduced RH-123’s absorptive transport, accompanied by an increase in its secretory transport. V. vinifera seed extract, however, increased both the absorptive and secretory transport of RH-123. A reduction in TEER was observed in the presence of V. vinifera extract, indicating the modulation of tight junction integrity. Conclusion: The ex vivo pharmacokinetics interactions recorded in the current study suggest that the co-administration of herbal medicines could alter the extent of membrane permeation of Western drugs.

journal of herbmed pharmacololgy

Pharmacokinetic interactions: The effects of selected herbal extracts on permeation of P-glycoprotein substrate drugs across excised pig intestinal tissue