title: Salviaolate Protects Rat Brain from Ischemia-Reperfusion Injury through Inhibition of NADPH Oxidase.
abstract: Salviaolate is a group of depside salts isolated from Danshen (a traditional Chinese herbal medicine), with ≥ 85 % of magnesium lithospermate B. This study aims to investigate whether salviaolate is able to protect the rat brain from ischemia/reperfusion injury and the underlying mechanisms. Rats were subjected to 2 h of cerebral ischemia and 24 h of reperfusion to establish an ischemia/reperfusion injury model. The neuroprotective effects of salviaolate at different dosages were evaluated. A dosage (25 mg/kg) was chosen to explore the neuroprotective mechanisms of salviaolate. Neurological function, infarct volume, cellular apoptosis, nicotinamide adenine dinucleotide phosphate-oxidase activity, and H2O2 content were measured. In a nerve cell model of hypoxia/reoxygenation injury, magnesium lithospermate B was applied. Cellular apoptosis, lactate dehydrogenase, nicotinamide adenine dinucleotide phosphate-oxidase activity, and H2O2 content were examined. Ischemia/reperfusion treatment significantly increased the neurological deficit score, infarct volume, and cellular apoptosis accompanied by the elevated nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 content in the rat brains. Administration of salviaolate reduced ischemia/reperfusion-induced cerebral injury in a dose-dependent manner concomitant with a decrease in nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 production. Magnesium lithospermate B (20 mg/kg) and edaravone (6 mg/kg, the positive control) achieved the same beneficial effects as salviaolate did. In the cell experiments, the injury (indicated by apoptosis ratio and lactate dehydrogenase release), nicotinamide adenine dinucleotide phosphate-oxidase activity and H2O2 content were dramatically increased following hypoxia/reoxygenation, which were attenuated in the presence of magnesium lithospermate B (10(-5) M), VAS2870 (nicotinamide adenine dinucleotide phosphate-oxidase inhibitor), or edaravone (10(-5) M). The results suggest that salviaolate is able to protect the brain from ischemia/reperfusion oxidative injury, which is related to the inhibition of nicotinamide adenine dinucleotide phosphate-oxidase and a reduction of reactive oxygen species production.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lou
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Kai-Di
authors.initials: KD
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Jing-Jie
authors.initials: JJ
authors.lastname: Peng
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Zhong-Bao
authors.initials: ZB
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Qi-Lin
authors.initials: QL
authors.lastname: Ma
authors.affiliation: Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Xiu-Ju
authors.initials: XJ
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001572:Benzofurans / Q000627:therapeutic use*; D001583:Benzoxazoles / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002545:Brain Ischemia / Q000517:prevention & control*; D002478:Cells, Cultured; D002681:China; D002934:Cinnamates / Q000627:therapeutic use*; D053630:Depsides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D014230:Triazoles / Q000494:pharmacology; D000097123:Rosmarinic Acid
chemical_list: D000975:Antioxidants; D001572:Benzofurans; D001583:Benzoxazoles; D002934:Cinnamates; D053630:Depsides; D004365:Drugs, Chinese Herbal; D019255:NADPH Oxidases; D018696:Neuroprotective Agents; D014230:Triazoles; D000097123:Rosmarinic Acid; C511179:3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5-d)pyrimidine; C046833:lithospermic acid; C061091:lithospermate B