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

Pharmacology. 2018;101(5-6):269-277. doi: 10.1159/000487144. Epub 2018 Mar 2.


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.

Keywords: Multidrug resistance; Benzaldehyde; Borneol; Muscone; P-glycoprotein; Vanillin.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Benzaldehydes / pharmacology*
  • Caco-2 Cells
  • Camphanes / pharmacology*
  • Chromatography, High Pressure Liquid
  • Cycloparaffins / pharmacology*
  • Flow Cytometry
  • Herb-Drug Interactions
  • Humans
  • Ileum / drug effects
  • Ileum / metabolism
  • Intestinal Absorption / drug effects
  • Jejunum / drug effects
  • Jejunum / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rhodamine 123 / pharmacokinetics
  • Vinblastine / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Benzaldehydes
  • Camphanes
  • Cycloparaffins
  • Rhodamine 123
  • Vinblastine
  • vanillin
  • isoborneol
  • benzaldehyde
  • muscone