Mechanistic studies of the transport of peimine in the Caco-2 cell model

Abstract

Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations <200 μmol/L, the effect of peimine concentration, pH, temperature, efflux transport protein inhibitors and EDTA-Na2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at pH 6.0 and 7.4, the Papp(AP-BL) of peimine is not significantly different but the Papp(BL-AP)) is; that both Papp(AP-BL) and Papp(BL-AP) at 4 °C are significantly higher than their corresponding values at 37 °C; that the P-glycoprotein (P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary, the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp.

Self-nanoemulsifying system improves oral absorption and enhances anti-acute myeloid leukemia activity of berberine

“…It readily forms monolayers with morphological and functional similarities to the human small intestinal epithelium. In fact the FDA now recognizes the Caco-2 cell monolayer as a viable model that replicates human intestinal absorption [ 52 ]. It does this not only because the cells form tight intercellular junctions similar to those of the intestinal epithelium but also because they express ATP-binding cassette (ABC) membrane transporters such as P-glycoprotein (P-gp) and multidrug resistance protein (MRP) that act to protect the body from toxic exogenous substances [ 53 ].…”

Use of fluorescein isothiocyanate isomer I to study the mechanism of intestinal absorption of fucoidan sulfate in vivo and in vitro

“…Caco-2 monolayer cell Transwell chamber model AP → BL transmembrane transport assay (Chai et al, 2016;Chen et al, 2016;Gallardo et al, 2016) was calculated according to the following formula:…”

Chloroplast genomic resources for phylogeny and DNA barcoding: a case study on Fritillaria

“…Within the realm of Chinese medicine, Fritillaria bulbs have heat clearing, expectorant, antitussive, detoxifying and analgesic properties and are used to treat conditions such as dry coughing, sputum with blood, umbilical carbuncle and acute mastitis 5 – 7 . Moreover, modern pharmacological studies have demonstrated that Fritillaria bulb extracts have therapeutic benefits for leukemia, liver cancer and cervical cancer as well as antitumor activity 6 , 8 . Each Fritillaria species used in traditional Chinese medicine has its own unique efficacy and active biological ingredients.…”