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摘要
OBJECTIVE To investigate the effect of menthol on intestinal absorption and its molecular mechanism. METHODS The rat everted intestinal sac model and Caco-2 cell monolayer model were established in vitro to investigate the effects of different concentrations of menthol on the intestinal absorption of salvianic acid A.After treating Caco-2 cells with 2 μmol·L-1, 8, 16 μmol·L-1menthol, 25 μmol·L-1verapamil, and 100 μmol·L-1ammonium pyrrolidine dithiocarbamate(PDTC) for 2 hours,P-gp protein, IκBα protein, p65 cytoplasmic protein and p65 nucleoprotein were detected by Western blot, Q-PCR method was used to detect the changes of MDR1 gene and IκBα gene expression. RESULTS The 0.1% menthol could significantly increase the drug absorption rate constant of salvianic acid A (P<0.05); 2 μmol·L-1menthol group and verapamil group AP-BL Papp were significantly higher than control group(P<0.05), and the 16 μmol·L-1menthol group AP-BL Pappwas lower than control group(P<0.01);AP-BL Pappof the 16 μmol·L-1menthol group was lower than that of the control group(P<0.01), there was no statistical difference in BL-AP among groups. After Caco-2 cells were administered for 2 hours, compared with the blank group, the 2,8 μmol·L-1menthol, 100 μmol·L-1PDTC, and 25 μmol·L-1verapamil significantly decreased the expression of MDR1 mRNA and P-gp protein(P< 0.05), the 2 μmol·L-1 menthol, 100 μmol·L-1 PDTC, and 25 μmol·L-1 verapamil significantly increased the expression of IκBα mRNA and IκBα protein (P<0.01), the p65 nucleoprotein level of the 2 μmol·L-1 menthol group, 8 μmol·L-1 menthol group, the PDTC group and the verapamil group were reduced(P<0.05), and the p65 cytoplasmic protein level was increased(P<0.05). CONCLUSION Low concentration of menthol can significantly promote the intestinal absorption of salvianic acid A, and its mechanism may be related to its regulation of NF-kB signaling pathway and inhibition of P-gp protein expression.
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