Cardioprotection with 8-O-acetyl shanzhiside methylester on experimental myocardial ischemia injury.
8-O-acetyl shanzhiside methylester (ND01) was isolated from the leaves of Lamiophlomis rotata (Benth.) Kudo. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effects of ND01 in vivo and elucidated the potential mechanism in vitro. The results indicated that ND01 significantly attenuated hypoxia-induced cytotoxicity in a concentration-dependent manner in H9c2 cells. Treatment of H9c2 cells with ND01 9 μM blocked TNF-α-induced nuclear factor kappaB (NF-κB) phosphorylation by blocking High-mobility group box1 (HMGB1) expression. Treatment of rats with ND01 10mg/kg, (i.v.) protected the animals from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics and reduction of myocardial damage severity. Treatment with ND01 also lowered serum levels of pro-inflammatory factors and reduced High mobility group box-1 protein (HMGB1) and phosphorylated NF-κB expression in ischemic myocardial tissue. Additionally, continuous i.v. of ND01 14 days attenuated cardiac remodeling. These protective effects suggested that ND01 might be due to block of myocardial inflammatory cascades through an HMGB1-dependent NF-κB signaling pathway.
School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, PR China.
Ze-Chun
ZC
Kang
Wang-Lin
WL
Jiang
Yong
Y
Xu
Hai-Bo
HB
Zhu
Jian
J
Hou
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
D002316:Cardiotonic Agents; D005960:Glucosides; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D015850:Interleukin-6; D016328:NF-kappa B; D011714:Pyrans; D014409:Tumor Necrosis Factor-alpha; C099473:8-O-acetyl shanzhiside methyl ester; D003094:Collagen