Attenuation Mechanism of Aconti Lateralis Radix Praeparata Combined with Glycyrrhizae Radix et Rhizoma Based on Heart CYP450 Isozymes / 中国实验方剂学杂志

ABSTRACT

<b>Objective:To investigate the effect of Aconiti Lateralis Praeparata Radix combined with Glycyrrhizae Radix et Rhizoma on mRNA expression of cytochrome P450 (CYP450) enzymes in rat' s heart. <b>Method:Male Sprague Dawley rats were randomly divided into the control group, the inducer group (0.08 g·kg^-1·d^-1), the aconite group (0.5 g·kg^-1·d^-1), the licorice group (0.5 g·kg^-1·d^-1) and the compatibility group (aconite and licorice group 0.5 g·kg^-1·d^-1), with 6 rats in each group. In each group, the serum concentrations of aspartate transaminase (AST), creatine kinase (CK) andlactate dehydrogenase (LDH) were respectively measured. Hematoxylin-eosin(HE) staining was used to detect the pathologic changes in the heart tissue of the rats. The expression of several CYP genes were measured. <b>Result:After combination, the contents of AST, CK and LDH were lower than those of the aconite group. At the same time, the pathological results showed cardiac injury in rats in the aconite group, and licorice could alleviate the cardiac injury caused by aconite. At the level of gene transcription, the glycyrrhizae group could up-regulate the expressions of CYP2C11 and CYP2J3 to different degrees (<italic>P</italic><0.05), and the combination of licorice and aconite could up-regulate the expression of CYP2B1, CYP2C11 and CYP2J3 family (<italic>P</italic><0.05). It suggested that the combination could promote the formation of EETs in arachidonic acid(AA) metabolism, and the aconite could up-regulate the expressions of CYP4A1, CYP4A3, CYP4F5 and CYP4F6 in CYP4 family (<italic>P</italic><0.05), promote the formation of 20-hydroxyeicosatetraenoic acid(20-HETE). The combination of aconite and licorice can weaken the ability of aconite, down-regulate the expression of CYP4A3, CYP4F1, CYP4F5 and CYP4F6 family mRNA (<italic>P</italic><0.05), inhibit the formation of 20-HETE and reduce the cardiotoxicity caused by aconite. <b>Conclusion:The combination of licorice and aconite can regulate the expression of CYP450 enzyme in the heart, increase the production of EETs and the content of 20-HETE, and finally play a role in reducing toxicity.