SMND-309, a novel derivate of salvianolic acid B, ameliorates cerebral infarction in rats: characterization and role
| Autor: | Zhifeng Liu, Guisheng Li, Shumin Zhang, Jingwei Tian, Fenghua Fu, Youlei Wang, Yubai Gao |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Antioxidant Time Factors medicine.medical_treatment Ischemia Pharmacology Neuroprotection Severity of Illness Index Brain ischemia Superoxide dismutase Electron Transport Rats Sprague-Dawley chemistry.chemical_compound Adenosine Triphosphate Caffeic Acids Malondialdehyde medicine Animals Molecular Biology Membrane Potential Mitochondrial Analysis of Variance Glutathione Peroxidase biology Dose-Response Relationship Drug Cerebral infarction business.industry Superoxide Dismutase General Neuroscience Brain Infarction Middle Cerebral Artery medicine.disease Mitochondria Rats Mitochondrial respiratory chain Neuroprotective Agents chemistry Anesthesia biology.protein Neurology (clinical) business Energy Metabolism Developmental Biology |
| Zdroj: | Brain research. 1263 |
| ISSN: | 1872-6240 |
| Popis: | (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. |
| Databáze: | OpenAIRE |
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