In vitro assessment of increasing cytotoxicity of Veratrum nigrum induced by Panax ginseng / 军事医学

ABSTRACT

Objective To compare the potential cytotoxicity induced by Veratrum nigrum coadministered with Panax ginseng, and to provide experimental evidence on the mode of herb-herb interaction based on human liver drug metabolizing enzymes.Methods The effect of V.nigrum and coadministration on cultured human hepatoma (HepG2) cells was investi-gated by detecting morphological changes , cell viability , cytomembrane integrity and apoptosis after the cells were treated for 24 h.The mRNA expression levels of drug metabolizing enzymes influenced by P.ginseng were determined by real-time quantitative reverse-transcriptase polymerase chain reaction .Results V.nigrum coadministered with P.ginseng had a better inhibitive effect on the growth of HepG2 cells at the IC50value of (15.18 ±1.03) mg/ml than at the value of IC50 (21.46 ±1.10) mg/ml of V.nigrum.Coadministration more significantly raised the LDH level in cell culture medium than at the same dose of V.nigrum.Moreover, in coadministration group, compared with the same dose of V.nigrum,the total apoptosis and necrosis of HepG2 cells were significantly increased .P.ginseng had effect on the expression of CYP3A4, CYP1A1, CYP1A2, CYP2B6 and CYP2E1 mRNA.Conclution Compatibility of medicines in a prescription also has herb-herb interactions based on drug metabolizing enzymes .The interaction mode is that the P.ginseng inhibits and induces CYPs and the modulated CYP isozymes ,inturn,have an impact on the metabolism of constituens in coadministered herbs causing herb-herb interaction .