The use of nano emulsion has improved the bioavailability of paeonol, and that is mainly because of the P-glycoprotein (P-gp)-mediated efflux described in our previous study. However, other mechanisms involved in the ...The use of nano emulsion has improved the bioavailability of paeonol, and that is mainly because of the P-glycoprotein (P-gp)-mediated efflux described in our previous study. However, other mechanisms involved in the intestinal absorption of paeonol nanoemulsion are still unknown. Therefore, we aimed to investigate additional paeonol nanoemulsion absorption mechanisms. By establishing the Caco-2 cells model and the follicle-associated epithelium (FAE) model, uptake studies and bidirectional transport of paeonol nanoemulsion in the presence of different efflux inhibitors were conducted to observe its intake and transport. The paracellular pathway was evaluated by fluorescent staining of Occludin, and the expressions of efflux proteins and tight junction proteins were detected by Western blotting analysis. In this study, we found that nanoemulsion improved the absorption of paeonol by increasing its uptake across the Caco-2 and FAE cells and by reducing the expressions of efflux proteins. In addition, paeonol nanocmulsion had no effect on the opening of tight junctions. The results showed that the absorption of paeonol nanoemulsion occurred by passive diffusion in the Caco-2 cell mode! and by endocytosis in the FAE model, which was related to multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) efflux. Paeonol nanoemulsion significantly in creased the absorption of the drug in intestinal cells, which was possibly related to the increase in intestinal cell uptake, inhibited expressions of efflux protein and reduction of drug efflux.展开更多
基金National Nature Science Foundation of China(Grant No.81773937,81873038)
文摘The use of nano emulsion has improved the bioavailability of paeonol, and that is mainly because of the P-glycoprotein (P-gp)-mediated efflux described in our previous study. However, other mechanisms involved in the intestinal absorption of paeonol nanoemulsion are still unknown. Therefore, we aimed to investigate additional paeonol nanoemulsion absorption mechanisms. By establishing the Caco-2 cells model and the follicle-associated epithelium (FAE) model, uptake studies and bidirectional transport of paeonol nanoemulsion in the presence of different efflux inhibitors were conducted to observe its intake and transport. The paracellular pathway was evaluated by fluorescent staining of Occludin, and the expressions of efflux proteins and tight junction proteins were detected by Western blotting analysis. In this study, we found that nanoemulsion improved the absorption of paeonol by increasing its uptake across the Caco-2 and FAE cells and by reducing the expressions of efflux proteins. In addition, paeonol nanocmulsion had no effect on the opening of tight junctions. The results showed that the absorption of paeonol nanoemulsion occurred by passive diffusion in the Caco-2 cell mode! and by endocytosis in the FAE model, which was related to multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) efflux. Paeonol nanoemulsion significantly in creased the absorption of the drug in intestinal cells, which was possibly related to the increase in intestinal cell uptake, inhibited expressions of efflux protein and reduction of drug efflux.
