Intestinal absorption mechanisms of berberine, palmatine, jateorhizine, and coptisine: involvement of P-glycoprotein

Abstract

1. The absorption and transport mechanisms of berberine, palmatine, jateorhizine, and coptisine were studied using a Caco-2 cells uptake and transport model, with the addition of cyclosporin A and verapamil as P-glycoprotein (P-gp) inhibitors and MK-571 as a multidrug resistance-associated protein 2 (MRP₂) inhibitor.

2. In the uptake experiment, berberine, palmatine, jateorhizine, and coptisine were all taken into Caco-2 cells, and their uptakes were increased in the presence of cyclosporin A or verapamil.

3. In the transport experiment, P_app (AP-BL) was between 0.1 and 1.0 × 10⁶ cm/sec for berberine, palmatine, jateorhizine, and coptisine and was lower than P_app (BL-AB). ER values were all >2. Cyclosporin A and verapamil both increased P_app (AP-BL) but decreased P_app (BL-AB) for berberine, palmatine, jateorhizine, and coptisine; ER values were decreased by >50%. MK-571 had no influence on the transmembrane transport of berberine, palmatine, jateorhizine, and coptisine.

4. At a concentration of 1–100 μM, berberine, palmatine, jateorhizine, and coptisine had no significant effects on the bidirection transport of Rho123.

5. Berberine, palmatine, jateorhizine, and coptisine were all P-gp substrates; and at the range of 1–100 μM, berberine, palmatine, jateorhizine, and coptisine had no inhibitory effects on P-gp.

Keywords::

• Coptis chinensis
• isoquinoline alkaloids
• transport
• Caco-2 cells
• P-gp
• MRP2

Acknowledgements

The first author sincerely acknowledged native English-speaking experts of BioMed Proofreading for the support of the manuscript preparation.

Declarations of interest

This study was supported by the Doctor Subject Foundation of the Ministry of Education of China (Grant No. 200802680010), by the project of Shanghai Natural Science Founding (Grant No. 10ZR1430800), by the National Major Program for Clinical Evaluation Research Technology platform of Viral Hepatitis Novel Traditional Chinese Medicine Production (Grant No. 2008ZX09312-023), by the Shanghai Leading Academic Discipline Project (Grant No. J50303), and by the Construction Program for Innovative Research Team in Shanghai Institutions of Higher Education.