The inhibitory effects of mitragynine on P-glycoprotein in vitro.

摘要: Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity fatal cases involving mitragynine kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) multidrug transporter which modulates pharmacokinetics of xenobiotics plays key role in mediating drug-drug interactions. This study investigated effects on P-gp transport activity, mRNA, protein expression Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, immunocytochemistry techniques, respectively. Molecular docking simulation revealed that interacts with important residues at nucleotide binding domain (NBD) site structure not substrate site. was consistent subsequent experimental work as exhibited low permeability across cell monolayer inhibited digoxin 10 μM, similar to quinidine. The reduction activity vitro further contributed by downregulation mRNA P-gp. In summary, likely inhibitor substrate. Hence, concurrent administration mitragynine-containing products psychoactive drugs are substrates may lead clinically significant toxicity. Further clinical prove this point needed.