Inhibitory Effects of Benzaldehyde, Vanillin, Muscone and Borneol on P-Glycoprotein in Caco-2 Cells and Everted Gut Sac

Abstract

Aims: In clinical practice, herbal medicines have played an important role in the modulation of drug transporters through the combination of conventional prescription drugs, which necessitates the elucidation of herb-drug interactions. The present study was designed to investigate the inhibitory effects and mechanisms of benzaldehyde, vanillin, muscone, and borneol on P-glycoprotein (P-gp). Methods: The effects of the 4 compounds on the intracellular accumulation of rhodamine-123 (Rho-123) in vinblastine-treated Caco-2 (VB-Caco-2) cells were studied by monitoring fluorescence intensity through a flow cytometry assay, and the effects of these compounds on Rho-123 transport through VB-Caco-2 monolayers and Rho-123 intestinal absorption in the rat everted gut sac were investigated by high-performance liquid chromatography. Moreover, P-gp expression in VB-Caco-2 cells was assessed using flow cytometry and Western blot analysis, and the relative ABCB1 mRNA level was determined by Real-time RT-PCR. Key Findings: The results showed that benzaldehyde, vanillin, muscone, and borneol significantly increased Rho-123 uptake in VB-Caco-2 cells, increased the absorption rate and apparent permeability coefficient of Rho-123 in rat jejunum and ileum, and decreased the efflux ratio of Rho-123 from 6.52 to less than 2 during transport across VB-Caco-2 cell monolayers. In addition, these compounds reduced the protein and ABCB1 mRNA levels of P-gp in VB-Caco-2 cells. Conclusions: These data indicate that benzaldehyde, vanillin, muscone and borneol could effectively reverse multidrug resistance via inhibiting the P-gp function and expression pathway. The data provide fodder for further investigation into the interaction between the 4 compounds and other drugs transported by P-gp.

Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization

“…It is a simple, fast, economic, and reproducible method for predicting drug permeability and evaluating the performance of drug delivery systems (Wang et al. 2018 ). The ex vivo rat permeation profile and intestinal apparent permeability results were presented in Figure 6(B) and Figure 6(C) .…”

Borneol influences the pharmacokinetics of florfenicol through regulation of cytochrome P450 1A2 (CYP1A2), CYP2C11, CYP3A1, and multidrug resistance 1 (MDR1) mRNA expression levels in rats

“…He et al [10] suggested that borneol inhibits the P-gp-mediated efflux system, and thereby improves the intestinal absorption of drugs. Wang et al [33] reported that borneol increases the absorption rate and apparent permeability coefficient of Rho-123 in the rat jejunum and ileum.…”

Inhibitory effects of Triphala on CYP isoforms in vitro and its pharmacokinetic interactions with phenacetin and midazolam in rats

“…The mobile phase consisted of a solution of acetonitrile and water at a ratio of 35:65. The flow rate of mobile phase was 0.8 mL/min ( Wang et al., 2018 ). The apparent permeability coefficient ( P app ) of Rho-123 across Caco-2 cells was calculated according to Eq.…”