Protections of SMND-309, a novel derivate of salvianolic acid B, on brain mitochondria contribute to injury amelioration in cerebral ischemia rats.
SMND-309, a novel compound named (2E)-2-{6-[(E)-2-carboxylvinyl]-2,3-dihydroxyphenyl}-3-(3,4-dihydroxyphenyl) propenoic acid, is a new derivate of salvianolic acid B. The present study was conducted to investigate whether SMND-309 has a protective effect on brain injury after focal cerebral ischemia, and if it did so, to investigate its effects on brain mitochondria. Adult male SD rats were subjected to middle cerebral artery occlusion (MCAO) by bipolar electro-coagulation. Behavioral tests and brain patho-physiological tests were used to evaluate the damage to central nervous system. Origin targets including mitochondria production of reactive oxygen species, antioxidant potentia, membrane potential, energy metabolism, mitochondrial respiratory enzymes activities and mitochondria swelling degree were evaluated. The results showed that SMND-309 decreased neurological deficit scores, reduced the number of dead hippocampal neuronal cells in accordance with its depression on mitochondria swelling degree, reactive oxygen species production, improvements on mitochondria swelling, energy metabolism, membrane potential level and mitochondrial respiratory chain complex activities. All of these findings indicate that SMND-309 exerted potent neuroprotective effects in the model of permanent cerebral ischemia, contributed to its protections on brain mitochondrial structure and function.
Tian
Jingwei
J
School of Pharmacy, Yantai University, Yantai, Shangdong, PR China.
Fu
Fenghua
F
Li
Guisheng
G
Gao
Yubai
Y
Zhang
Yunjuan
Y
Meng
Qingsheng
Q
Li
Changlu
C
Liu
Fu
F
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001572:Benzofurans / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy*; D002109:Caffeic Acids / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D010946:Plants, Medicinal / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry* / Q000378:metabolism; D053630:Depsides
D000975:Antioxidants; D001572:Benzofurans; D002109:Caffeic Acids; D018696:Neuroprotective Agents; D010936:Plant Extracts; C539487:2-(6-(2-carboxyvinyl)-2,3-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)acrylic acid; C076944:salvianolic acid B; D053630:Depsides