Effect of hypaconitine combined with liquiritin on the expression of calmodulin and connexin43 in rat cardiac muscle in vivo.
OBJECTIVE
To study the effects of hypaconitine used alone and combined with liquiritin on calmodulin (CaM) expression and connexin43 (Cx43) phosphorylation on serine368 (Ser368), as well as to investigate the intervention of liquiritin on these hypaconitine-induced effects.


METHODS
Adult Wistar rats were orally administered hypaconitine (0.23, 0.69, 2.07 mg/kg per day), liquiritin (20 mg/kg per day), or hypaconitine (2.07 mg/kg per day) plus liquiritin (20 mg/kg per day) for seven consecutive days. The mRNA expression levels of CaM and Cx43 in rat myocardial tissue were determined by real-time quantitative PCR. The protein contents of CaM and phosphorylated Cx43 (Ser368) were determined by Western blot.


RESULTS
The results indicated that the mRNA and protein expression levels of CaM were significantly decreased by hypaconitine used alone and combined with liquiritin. Although CaM mRNA expression level was inhibited by liquiritin, its protein expression level was upregulated. Meanwhile, although no obvious effect on Cx43 mRNA expression was observed after the drug administration, the phosphorylation level of Cx43 (Ser368) was significantly inhibited. Furthermore, the coadministration of hypaconitine and liquiritin significantly reduced hypaconitine-induced inhibitory action on Cx43 (Ser368) phosphorylation.


CONCLUSIONS
The study indicated that hypaconitine could inhibit CaM expression and Cx43 (Ser368) phosphorylation, and liquiritin could interfere with this kind of effect by synergistically inhibiting CaM expression and by antagonizing Cx43 (Ser368) dephosphorylation induced by hypaconitine.
Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei University, Wuhan, China.
Mingjing
M
Yi
Wei
W
Peng
Xiaomin
X
Chen
Junjun
J
Wang
Yong
Y
Chen
D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D002147:Calmodulin / Q000235:genetics*; D018031:Connexin 43 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D044950:Flavanones / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
D002147:Calmodulin; D018031:Connexin 43; D044950:Flavanones; D005960:Glucosides; D012333:RNA, Messenger; C058309:hypaconitine; C512196:liquiritin; D000157:Aconitine