Absorption mechanism of oxymatrine in cultured Madin–Darby canine kidney cell monolayers

Abstract

Context Oxymatrine (OMT) is beneficial to human health by exerting various biological effects. Objective To investigate the absorption mechanism of OMT and discover absorption enhancers using Madin–Darby canine kidney (MDCK) cell monolayers.

Materials and methods Concentration effects on the transport of OMT were measured in the range of 1.0 × 10⁻⁵–1.0 × 10⁻³ M in 2 h. Then, the effect of time, direction, temperature and pH on the transport of OMT at 10⁻⁴ M was studied. Moreover, P_app of OMT was determined in the absence/presence of cyclosporine and surfactants at 100 μM to further confirm the relative transport mechanism.

Results The P_{app AP→BL} ranged from (3.040 ± 0.23) × 10⁻⁶ to (3.697 ± 0.19) × 10⁻⁶cm/s as the concentration varied from 10⁻⁵ to 10⁻³ M. OMT showed similar P_app at 4 and 37 °C (p > 0.05). Increasing the apical pH 7.4 and 8.0 resulted in P_app versus pH 5.0 (p < 0.01). Furthermore, in the presence of cyclosporine and surfactants including sodium citrate, sodium dodecyl sulphate (SDS) and deoxysodium cholate, P_app was (0.318 ± 0.033) × 10⁻⁵, (0.464 ± 0.048) × 10⁻⁵, (0.897 ± 0.115) × 10⁻⁵ and (1.341 ± 0.122) × 10⁻⁵cm/s, respectively. In the presence of surfactants, P_app significantly increased up to 1.5–4.3-fold (p < 0.05).

Discussion and conclusion OMT transport across MDCK cell monolayers was by passive diffusion. Sodium citrate, SDS and deoxysodium cholate serve as excellent absorption enhancers which are useful for the related research improving the oral bioavailability of OMT.

Keywords:

• Absorption enhancers
• LC–MS
• MDCK cells
• passive transport

Disclosure statement

The authors declare no conflicts of interest.

Funding information

This work was supported by National Natural Science Foundation of China (81073141), Guangdong Provincial Natural Science Foundation (9152402301000007) and Guangdong Province ‘12-5’ medical key subject.