RESUMO
OBJECTIVE To investigate the inhibitory effect of eight lignan compounds of Fructus Schisandrae chinensis in vitro on carboxylesterase 2 (CES2) and to estimate the herb-drug interaction (HDI) risks of strong CES2 inhibitors selected from the above compounds. METHODS Fluorescein diacetate (FD) was employed as a specific fluorescent probe of CES2. The residual activity of CES2 was detected in human liver microsomes after the intervention with deoxyschizandrin, schisanhenol, schisantherin E, schisandrol A, schisandrol B, gomisin J, gomisin G, and gomisin O at 37℃ for 10 min, respectively. 1% DMSO served as control. Residual activity of CES2 was assessed with metabolite production of FD detected by fluorescent intensity, combined with IC50 values of the above compounds to predict HDI risks between lignans and CES2-metabolizing drugs. RESULTS Compared with control group, the activity of CES2 was significantly inhibited by deoxyschizandrin and schisanhenol (P<0.01), with IC50 values of 8.06 μmol · L- 1 and 8.91 μmol · L- 1, respectively. The other six lignans compounds exhibited mild inhibitory effect on CES2. HDI risk prediction of deoxyschizandrin or schisanhenol indicated that exposure of CES2-metabolizing drugs might increase 11.24 and 0.40 times, respectively. CONCLUSION Deoxyschizandrin and schisanhenol exhibit strong inhibitory effects against CES2 in vitro so that potential HDI risks should be taken into account during administration of drugs containing Fructus Schisandrae chinensis.
