SMND-309, a novel derivate of salvianolic acid B, ameliorates cerebral infarction in rats: characterization and role.
(2E)-2-{6-[(E)-2-carboxylvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, a novel compound designated SMND-309, is a new degradation product of salvianolic acid B. The present study was conducted to evaluate whether SMND-309 has a protective effect on permanent focal cerebral ischemia in rats. The results showed that SMND-309 at doses higher than 4.0 mg/kg (i.v.) produced a significant neuroprotection in focal ischemia rats when administered 30 min after the onset of ischemia. SMND-309 (25.0 mg/kg, i.v.) demonstrated significant neuroprotective activity even after delayed administration at 1 h, 3 h and 6 h after ischemia. The neuroprotective effect of SMND-309 (25.0 mg/kg, bolus injection intravenous at 30 min after middle cerebral artery occlusion) was still present 7 days after ischemia. Meanwhile, SMND-309 significantly increased the brain ATP content, improved mitochondrial energy metabolism and mitochondrial respiratory chain complex activities and attenuated the elevation of malondialdehyde (MDA) content, the decrease in superoxide dismutase (SOD) and glutathione-peroxidase (GSH-Px) activity in brain mitochondria. All of these findings indicate that SMND-309 exerts potent and long-term neuroprotective effects with a favorable therapeutic time-window in the model of permanent cerebral ischemia, and its protective effects may be due to the amelioration of cerebral mitochondrial energy metabolism and the antioxidant property.
Tian
Jingwei
J
School of Pharmacy, Yantai University, Yantai, Shangdong, PR China.
Fu
Fenghua
F
Li
Guisheng
G
Wang
Youlei
Y
Gao
Yubai
Y
Liu
Zhifeng
Z
Zhang
Shumin
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002109:Caffeic Acids / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
C539487:2-(6-(2-carboxyvinyl)-2,3-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)acrylic acid; D002109:Caffeic Acids; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase