Cardioprotective effect of SMND-309, a novel derivate of salvianolic acid B on acute myocardial infarction in rats.
(2E)-2-{6-[(E)-2-carboxyvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, a novel compound designated SMND-309, is a new derivate of salvianolic acid B. The present study was designed to investigate the cardioprotective potential of SMND-309 and to elucidate the possible mechanisms on the basis of biochemical, histopathological and immunohistochemical studies in a rat model of acute myocardial infarction induced by permanent ligation of the left coronary artery. The results showed that treatment with SMND-309 via tail vein at doses of 10 and 20 mg/kg significantly prevented the elevation in ST segment level and the increase in serum creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase and cardiac troponin T content. Meanwhile, SMND-309 significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase, decreased the content of malondialdehyde in myocardium, and reduced the myocardium necrosis scores and the number of apoptosis cardiocytes in accordance with the up-regulated expression of anti-apoptotic protein, Bcl-2 and the down-regulated expression of proapoptotic protein, Bax. Moreover, SMND-309 exhibits significantly higher potency compared to salvianolic acid B at the same mg/kg but not the same mol/kg. These findings indicate that SMND-309 has a protective potential against myocardial infarction injury and the protective effects may be due to its scavenging lipid peroxidation products, increasing endogenous antioxidant defence enzymes and attenuating cardiocyte apoptosis.
Yang
Jianxiong
J
College of Life Science, Shaanxi Normal University, Xi'an, Shaanxi, China.
Zhang
Guanbo
G
Tian
Jingwei
J
Li
Chunmei
C
Jiang
Wanglin
W
Xing
Yanli
Y
Zhu
Haibo
H
Hou
Jian
J
Xu
Hong
H
Wu
Juan
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053630:Depsides
D000975:Antioxidants; D001572:Benzofurans; D002109:Caffeic Acids; D002316:Cardiotonic Agents; C539487:2-(6-(2-carboxyvinyl)-2,3-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)acrylic acid; C076944:salvianolic acid B; D053630:Depsides