ABSTRACT
Objective To investigate the effect of procyanidin on permeability of rodamin 123(R123)and fluorescein sodium (FS)via different intestinal mucosa in rat. Methods The cumulative permeability and the apparent permeability cofficient(Papp)of R123 and FS via rat intestinal membranes at the procyanidin concentration of 20 mg/L was evaluated by the method of Ussing Cham?ber. The concentrations of R123 and FS in the receptor samples were determined by fluorospectrophotometry. Results The absorptive directed permeability of R123 across all membranes was increased by co-administration of procyanidins,whereas that of the secretive direct was decreased. Compared with control group,the secretive directed permeability of R123 was significantly decreased in colon (P<0.01). Conclusion Procyanidin could inhibit the secretion of R123 on different intestinal mucosa which might be related to the inhibition of P-gp function.
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
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.
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Objective To validate the correlation between in vitro and in vivo absorption of capsaicin, and study the distribution of capsaicin in tissue after oral administration. Methods In situ closed loop method was used to measure the absorption of capsaicin from different intestine segments of rats. Concentrations of capsaicin in rat plasma were examined by LC-MS/MS and pharmacokinetic parameters were calculated by the software WinNonlin. Results The AUC0-240min and Cmax of capsaicin absorbed from colon were higher than those of ileum and jejunum. However, there was no statistic difference. Conclusion In the primary study, we realized that permeability of capsaicin across the colonic mucosa is remarkably higher than that across jejunal or ileac mucosa in mucosal-to-serosal direction. However, there′s no statistical difference for the absorption of capsaicin across different intestinal regions by in situ assay. These results suggest the correlation between in vitro and in situ method is worth further study.