Effects of borneol on the intestinal transport and absorption of two P-glycoprotein substrates in rats

Abstract

As the most prevalent route of delivery, oral administration has the challenge of potentially low bioavailability in part because P-glycoprotein (P-gp) in the intestinal tract affects absorption. Therefore, absorption enhancers or P-gp inhibitors are strategies to solve this problem. The aim of the present study was to investigate the effects of borneol on transportation of colchicine and rhodamine123, two P-gp substrates, in rats. In vitro transportation was assessed with a diffusion chamber system with isolated rat intestines. Different concentrations of borneol (10, 40 and 80 μg/mL) were prepared in solutions with two P-gp substrates compared with blank solutions. The in vivo effects on colchicine were assessed by a pharmacokinetic study. Borneol enhanced the absorptive transport of two P-gp substrates, which was relevant to the concentration. A pharmacokinetic study showed that in the presence of borneol, a significant increase in C(max) and AUC(0→8) of colchicine occurred when compared to colchicine alone. The study showed that borneol affected two P-gp substrates in the intestine, possibly by inhibiting the effects of P-gp and enhancing intestinal absorption of drugs. Therefore, borneol could be developed as a P-gp inhibitor and absorptive enhancer.

Hepatic, gastric and intestinal first‐pass effects of vitexin‐2′′‐O‐rhamnoside in rats by ultra‐high‐performance liquid chromatography

“…In the bile salts group, the plasma concentration of VR continually increased even at the end of the experiment because of the effect of bile salts on intestinal permeability, which can enhance intestinal absorption (Sharma et al ., 2005). A recent study declared that borneol has an impact on two P‐gp substrates, colchicine and rhodamine123, in the intestine owing to their inhibiting the effect of P‐gp and enhancing intestinal absorption, and it also pointed out that borneol could be developed as a P‐gp inhibitor and absorption enhancer (He et al ., ). Furthermore, borneol, as a traditional Chinese medicine, can enhance the blood–brain barrier permeability and accelerate the transportation of kaempferol to the brain (Zhang et al ., ), and this is the key reason for the high AUC of VR after infusing borneol, meaning that it is feasible to improve the bioavailability of VR by combining with borneol in future application in the clinic.…”

“…Considering that intestinal absorption was the main reason leading to the low bioavailability of VR, and therefore verapamil and cyclosporin A, common substrate/inhibitors of cytochrome P450 3A (CYP3A)/P‐glycoprotein (P‐gp), and midazolam, an inhibitor of CYP3A, were chosen to investigate the concurrent action of intestinal CYP3A/P‐gp, which creates an absorption barrier, affecting the systemic bioavailability of orally administered medications (Shen et al ., ; Johnson et al ., ; Gertz et al ., ; Yamano et al ., ). Furthermore, absorption enhancers such as bile salts or borneol combined with VR were assayed to investigate the effects on the intestinal absorption (Mrestani et al ., ; He et al ., ).…”

Investigating the bioavailabilities of olerciamide A via the rat's hepatic, gastric and intestinal first‐pass effect models

“…borneol can enhance the absorption of gastrodin in the gastrointestinal tract and promote its distribution to the brain (Cai et al, ) and significantly enhance the oral bioavailability of rifampicin (Cheng, Wu, & Feng, ). Research has also demonstrated that borneol was effective in inhibiting the P‐gp‐mediated efflux system, thereby improving the intestinal absorption of drugs (He et al, ). As both a P‐gp inhibitor and an absorption enhancer, borneol was used to improve the absorption of olerciamide A in this study.…”

“…It was found that an intestinal first‐pass effect was the main reason leading to the low bioavailability of olerciamide A, induced by CYP3A and P‐gp which are usually present in small bowel enterocytes, catalysing the substantial metabolism of some drugs and leading to the first‐pass effect (Watkins, ). Verapamil, an inhibitor both of CYP3A and P‐gp (Wang, Jones, & Hall, ), and midazolam, an inhibitor of CYP3A (Thummel et al, ), as well as borneol, both an inhibitor of P‐gp and an intestinal absorption enhancer (He, Shen, & Li, ), were therefore used in order to improve the bioavailability. Furthermore, administrations in different parts of the rectum have also been studied in order to provide a method for improving the bioavailability of olerciamide A.…”

Lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel for intracellular drug delivery to C6 glioma cells with P-gp inhibition and its tumor targeting

“…Some studies have demonstrated that borneol is able to loosen intercellular tight junctions [22] and inhibit the action of P-gp on the cell membrane [23]. We speculate that co-encapsulation of BOR and PTX could increase the uptake of PTX by the brain glioma cells.…”