Combined effect of Euphorbia kansui and Glycyrrhiza uralensis on metabolism of Kansuinine A and Kansuinine B / 中国药理学通报

ABSTRACT

Aim To study the combined effect Euphor-bia kansui of and Glycyrrhiza uralensis on metabolism of Kansuinine A and Kansuinine B. Methods Control, GU and GU plus EK groups were treated for 10 days, respectively. Then the liver microsomes were pre-pared. KA and KB were incubated with microsomes of each group, and concentrations of KA and KB were measured to reflect the metablism of KA and KB. E-rythromycin, diphenhydramine hydrochloride,benzbro-marone, cimetidine, fluconazole the inhibitors of CYP3 A4 , CYP2 D6 , CYP2 C9 , CYP1 A2 , CYP2 C19 respectively, were incubated with KA and KB. Con-centrations of KA and KB were measured to reveal the cytochrome P450 isoforms which involved in the metab-olism of them. KA and KB were incubated with glycyr-rhizic acid and enoxolone. Then concentrations of KA and KB were measured to reveal the effects of glycyr-rhizic acid and enoxolone to KA and KB. Results Concentrations of KA and KB in GU plus EK group were significantly higher than those in control and EK groups, which showed that the metablisom of KA and KB was inhibited in GU plus EK group. In addition, concentrations of KA and KB were higher in microsomes incubated with erythromycin, diphenhydramine hydrochloride, benzbromarone, cimetidine and fluconazole than in control group, which revealed that the metablism of KA and KB was slowed down when CYP3A4, CYP2D6, CYP2C9, CYP1A2 and CYP2C19 were inhibited. They may participate in the metablisom of KA and KB. After incubation with glycyrrhizic acid and enoxolone, the metablism of KA and KB was slowed down. Conclusions KA and KB may be the substrates of CYP2C19. GU plus EK can inhibit the activity of CYP2C19, which resulted in KA and KB metablism slowing down and accumulation. In addition, glycyrrhizic acid and enoxolone can inhibit the metablism of KA and KB. It may be one of the reasons of increased toxicity of GU plus EK.