title: ND-309, a novel compound, ameliorates cerebral infarction in rats by antioxidant action.
abstract: Extract of danshen (Salvia miltiorrhiza Bunge.) has been clinically prescribed in China to treat patients with stroke. The novel compound designated ND-309, namely isopropyl-beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropanoate is a new metabolite of danshen in rat brain. The present study was conducted to investigate whether ND-309 has a protective effect on brain injury after focal cerebral ischemia, and to determine the possible mechanism. Adult male SD rats were subjected to middle cerebral artery occlusion (MCAO) by bipolar electro-coagulation. Behavioral tests were used to evaluate the damage to central nervous system. The cerebral infarct volume and edema were assessed to evaluate the brain patho-physiological changes. Spectrophotometric or spectrofluorometric assay methods were used to determine the generation of reactive oxygen species (ROS), activities of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-Px), contents of malondialdehyde (MDA) and adenosine triphosphate (ATP), as well as respiratory control ratio of the brain mitochondria. The results showed that treatment with ND-309 significantly decreased neurological deficit scores, reduced infarct volume and the edema compared with the model group. Meanwhile, ND-309 significantly increased the brain ATP content, improved mitochondrial energy metabolism, attenuated the elevation of MDA content, the decrease in SOD, GSH-Px activity and the generation of ROS in brain mitochondria. All of these findings indicate that ND-309 has the protective potential against cerebral ischemia injury and its protective effects may be due to the amelioration of cerebral energy metabolism and its antioxidant property.
authors.affiliation: School of Pharmacy, Yantai University, Yantai, Shangdong 264005, PR China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
authors.forename: Guisheng
authors.initials: G
authors.lastname: Li
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhang
authors.forename: Guiwu
authors.initials: G
authors.lastname: Qu
authors.forename: Wanglin
authors.initials: W
authors.lastname: Jiang
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza; D013482:Superoxide Dismutase / Q000187:drug effects
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; C028972:dan-shen root extract; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase