Interactions Between Emodin and Efflux Transporters on Rat Enterocyte by a Validated Ussing Chamber Technique

Abstract

Emodin, a major active anthraquinone, frequently interacts with other drugs. As changes of efflux transporters on intestine are one of the essential reasons why the drugs interact with each other, a validated Ussing chamber technique was established to detect the interactions between emodin and efflux transporters, including P-glycoprotein (P-gp), multidrug-resistant associated protein 2 (MRP2), and multidrug-resistant associated protein 3 (MRP3). Digoxin, pravastatin, and teniposide were selected as the test substrates of P-gp, MRP2, and MRP3. Verapamil, MK571, and benzbromarone were their special inhibitors. The results showed that verapamil, MK571, and benzbromarone could increase digoxin, pravastatin, and teniposide absorption, and decrease their Er values, respectively. Verapamil (220 μM) could significantly increase emodin absorption at 9.25 μM. In the presence of MK571 (186 μM), the Papp values of emodin from M-S were significantly increased and the efflux ratio decreased. With the treatment of emodin (185, 370, and 740 μM), digoxin absorption was significantly decreased while teniposide increased. These results indicated that emodin might be the substrate of P-gp and MRP2. Besides, it might be a P-gp inducer and MRP3 inhibitor on enterocyte, which are reported for the first time. These results will be helpful to explain the drug–drug interaction mechanisms between emodin and other drugs and provide basic data for clinical combination therapy.

Enhanced Oral Absorption and Liver Distribution of Polymeric Nanoparticles through Traveling the Enterohepatic Circulation Pathways of Bile Acid

“…As is well known, three key processes are generally involved in transcytosis of the nanoparticles: endocytosis at AP side, intracellular transport through cytoplasm, and exocytosis at BL side. As for the intestinal absorption of bile acid in which ASBT, IBABP, OSTα-OSTβ, and MRP3 play a programmable mediation role, − an analogous situation was also expected for the transcytosis of DA-conjugated micelles via mediation of these transporters. To examine this issue, three inhibitors of the bile acid transporters were selected to pretreat the monolayer to assess their effect on the transcellular transport of the micelles.…”

Effect of Rumex Acetosa Extract, a Herbal Drug, on the Absorption of Fexofenadine

“…Ostensibly harmless natural products—such as juices, fruits, vegetables and herbal products in the form of ayurvedic medicine—have been reported in several studies to potentially cause many drug interactions affecting drug absorption mediated by transporters [ 41 , 42 ]. For example, emodin—a potential antineoplastic drug and a major component of the Rhamnus, Rumex, Aloe , Rheum and Cassia species—has been reported to be a possible P -gp inducer [ 26 ] or an inhibitor [ 18 ].…”

“…However, there have been few studies concerning drug interactions with herbal medicines involving both P -gp and OATP1A2. Furthermore, it has been reported that the emodin acts on P -gp as an inducer [ 26 ] or an inhibitor [ 18 ]. Our results clarify the inhibitory effect of emodin on the P -gp through in vitro and in vivo study.…”

Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium‑binding protein A8 and P‑glycoprotein

“…For P-gp, in order to investigate the effect of curcumin on its transport function, curcumin and RHO-123 were applied to K562/DOX cells simultaneously. Following incubation for 45 min, the intracellular RHO-123 levels were detected, with the P-gp-specific inhibitor VRP used as a positive control (47,48). The results suggested that when curcumin was applied to K562/DOX cells, the intracellular accumulation of RHO-123 increased significantly, indicating that curcumin inhibited the function of P-gp.…”