The major effective components in Shengmai Formula interact with sodium taurocholate co-transporting polypeptide.

Background: Shengmai Formula (SMF) is widely used to treat cardiovascular disease such as chronic heart disease, coronary atherosclerotic heart disease, viral myocarditis, and others. Our previous studies have shown that OATP1B1/1B3 mediates the interactions between ophiopogon D and ginsenoside Rb1/Rd, which are the major active components in SMF. The herb-drug interactions that involve sodium taurocholate co-transporting polypeptide (NTCP) have been drawing increasing amounts of attention.

Purpose: The aim of the present study was to investigate the interactions of the major effective components in SMF mediated by NTCP.

Methods: By using NTCP-overexpressing HEK293T cells and liquid chromatograph-mass spectrometer (LC-MS) analytical methods, we investigated the impact of the four main effective fractions and the 12 main effective components in SMF on NTCP-mediated sodium taurocholate (TCNa) uptake. The interactions of these effective components in SMF mediated by NTCP were further studied.

Results: The main effective fractions, ginseng total saponins (GTS), ophiopogon total saponins (OTS), ophiopogon total flavonoids (OTF), and fructus schisandrae total lignans (STL), all exhibited a certain inhibitory effect on the uptake of TCNa. Among the 12 main effective components, only ginsenoside Rg1, ophiopogon D', and schizandrin A showed inhibition of TCNa uptake, with IC values of 50.49 ± 4.24 μM, 6.71 ± 0.70 μM, and 45.80 ± 3.10 μM, respectively. Additionally, we found that ginsenoside Re and schizandrin B could be transported by NTCP-overexpressing HEK293T cells, and that the uptake of ginsenoside Re was significantly inhibited by OTS, OTF, STL, ginsenoside Rg1, ophiopogon D', and schizandrin A. The uptake of schizandrin B was significantly inhibited by GTS, OTS, OTF, and ophiopogon D'.

Conclusion: Ginsenoside Rg1, ophiopogon D', and schizandrin A are potential inhibitors of NTCP and may interact with clinical drugs mediated by NTCP. Ginsenoside Re and schizandrin B are also potential substrates of NTCP, and their uptake mediated by NTCP was inhibited by the other components in SMF. The interaction of complex components based on NTCP may be one of the important compatibility mechanisms in SMF.