Effect Of Hypaconitine Combined With Liquiritin On The Expression Of CaM And Cx43 In Rat Cardiac Muscle In Vitro And In Vivo

Fuzi, a traditional Chinese herb medicine, is used worldwide for its anti inflammatory, anti-tumor and immunoregulative activity. Because of the high toxicity of Fuzi, Licorice is commonly used to combine with Fuzi to reduce the toxicity of Fuzi clinically. Recently, the main studies focused on the analysis of chemical composition and electrophysiology after the compatibility of Fuzi with liquorice. It was reported that disorders of transfering Ca2+ and the hindrance of electrical coupling between cells have a close relation with arhythmia. In present study, we mainly focus our investigation on the CaM expression and Cx43 (Ser368) phosphorylation after the compatibility of Fuzi with liquorice, as well provide some experimantal evidence for the compatibility of Fuzi clinically.We applied Real-time PCR and Western Blot to investigate the effect of hypaconitine combined with liquiritin on the expression of CaM mRNA, protein expression and Cx43 mRNA, phosphorylated Cx43 (Ser368). In vivo, different concentration of hypaconitine could inhibit the expression of CaM mRNA and protein. Liquiritin could suppress CaM mRNA expression, but could induce CaM protein expression. The combination of hypaconitine and liquiritin could decreased the level of phosphorylated Cx43 (Ser368). Notably, it show an antagonism when phosphorylated Cx43 (Ser368) was down-regulated by hypaconitine. In vitro, it shows analogue results with the vivo's. Our results demonstrated that hypaconitine could affect both cardiac contraction and rhythm through suppressing CaM expression and Cx43 (Ser368) phosphorylation. Meanwhile, Liquiritin could suppress CaM expression when cooperate with hypaconitine and inhibit Cx43 (Ser368) phosphorylation which was down-regulated by hypaconitine, then affect the rhythm of myocardial cell. Taken together, Liquiritin could antagonism the arrhythmia by hypaconitine, which might be one of the molecular mechanism on the detoxification of Radix glycyrrhizae against Fuzi.