ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats.</p><p><b>METHODS</b>The permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp).</p><p><b>RESULTS</b>Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected.</p><p><b>CONCLUSION</b>Capsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.</p>
Subject(s)
Animals , Male , Rats , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Capsaicin , Pharmacology , Colon , Metabolism , Fluorescein , Pharmacokinetics , Ileum , Metabolism , Intestinal Absorption , Jejunum , Metabolism , Permeability , Rats, Sprague-Dawley , Rhodamine 123 , PharmacokineticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co-administered orally.</p><p><b>METHODS</b>Based on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively.</p><p><b>RESULTS</b>In Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63% in radix euphorbiae pekinensis group. The average AB% in verapamil group was about 1.5 times that of the blank group.</p><p><b>CONCLUSION</b>Co-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.</p>
Subject(s)
Animals , Rats , Administration, Oral , Biological Availability , Biological Transport , Chromatography, High Pressure Liquid , Euphorbiaceae , Chemistry , Paclitaxel , Pharmacokinetics , Permeability , Plant Extracts , Pharmacology , Plant Roots , Chemistry , Tandem Mass Spectrometry , VerapamilABSTRACT
Objective To investigate the effect of expression of microRNA-27a(miR-27a) and microRNA-451(miR-451) in A2780/T cells and its relativity to multidrug resistance (MDR)1 mRNA inhibition by procyanidin. Methods Stem-loop PCR method was performed to evaluate the expression of miR-27a and miR-451 in use of procyanidin (0-40μmol/L) in 0-48 h in A2780/T cells. Additionally, over-expressing or interfecting microRNAs by using mimics or inhibitor of miR-27a and miR-451, the expression of MDR1 mRNA was assessed by RT-PCR in cells exposing to procyanidin. Results The expression of miR-27a and miR-451 was significant inhibited by procyanidin in both time- and concentration-dependency. Over-expressed MDR1 mRNA associated with miR-27a or miR-451 mimics was blocked by procyanidin, whereas there was no effect on down-expressed MDR1 mRNA associated with miR-27a or miR-451 inhibitor by procyanidin. Conclusion Procyanidin inhibits MDR1 mRNA expression by inhibiting miR-27a and miR-451 expression in A2780/T cells.
