Mechanism Of Licorice To Reconcile Various Drug And Research On Its Hepato-protective Effect

Objective The effect of glycyrrhizin, which is a major component of Licorice on the expression of CYP3A4 mRNA and protein level was investigated in HepG2 cell. In this study,We explored the mechanism of regulation of CYP3A4 by glycyrrhizin initially. Furthermore, we also observed the hepato-protective effect of Licorice and glycyrrhizin on LCA-induced liver injure in mice, and provided experimental evidence for the theory of traditional Chinese medicine Licorice to reconcile various drugs and liver detoxification. Methods RT-PCR and Western-blot were used to detect glycyrrhizin on the expression of CYP3A4 mRNA and protein level. Futhermore, Using transient transfection of luciferase reporter gene assay and electrophoretic mobility shift assay, we have now investigated the mechanism of inductive effect on CYP3A4 by glycyrrhizin. Finally, we oberseved the hepato-protective effect by Licorice and glycyrrhizin in excessive LCA induced liver injury mice. Results Treatment with glycyrrhizin up-regulated the mRNA level of CYP3A4 in a time- and concentration-depedent manner in HepG2 cell, and protein level were also up-regulated. Moreover,reporter gene assay and electrophoretic mobility shift assay showed that glycyrrhizin treatment increased the transactivation activity of PXR and further produce inductive effect on CYP3A, and that is probably the reason why its mRNA and protein expression were up-regulated by glycyrrhizin. Animal experiments showed that Licorice and each group of glycyrrhizic can effectively decrease the high level of Peripheral ALT and AST in LCA-induced liver injury mice, Histopathological examination revealed that LCA induced hepatic necrosis, steatosis and inflammatory cell infiltration were markedly reversed by preadministration with Licorice and glycyrrhizin. The hepato-protective effect maybe related to regulation of key genes SHP, CYP7A1 and CYP3A11 expression which involved in bile acid synthesis and metabolism. Conclusions Licorice and its major component glycyrrhizin have the inductive effect on CYP3A4 enzyme, and probably have herb-drug interaction based on P450. Mechanism of Licorice to reconcile various drug maybe related to induction of CYP3A4 expression, thus accelerated the metabolism of co-administrated TCM or toxic constitutes in other TCMs, and then cause the toxicity decreasing. This induction processs maybe modulated via glycyrrhizin-PXR-CYP3A4 pathway. Meanwhile, animal experiment may provide experimental evidence for the research on Licorice and molecular mechanism of liver detoxification.