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: Zheng Lou, Kai-Di Ren, Bin Tan, Jing-Jie Peng, Xian Ren, Zhong-Bao Yang, Bin Liu, Jie Yang, Qi-Lin Ma, Xiu-Ju Luo, Jun Peng
• Journal: Planta medica (Planta Med) Vol. 81 Issue 15 Pg. 1361-9 (Oct 2015) ISSN: 1439-0221 [Electronic] Germany
• PMID: 26252829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• 3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5-d)pyrimidine
• Antioxidants
• Benzofurans
• Benzoxazoles
• Cinnamates
• Depsides
• Drugs, Chinese Herbal
• Neuroprotective Agents
• Triazoles
• lithospermic acid
• lithospermate B
• NADPH Oxidases
• rosmarinic acid

Topics

• Animals
• Antioxidants (therapeutic use)
• Benzofurans (therapeutic use)
• Benzoxazoles (pharmacology)
• Brain (drug effects, enzymology)
• Brain Ischemia (prevention & control)
• Cells, Cultured
• China
• Cinnamates (therapeutic use)
• Depsides (therapeutic use)
• Disease Models, Animal
• Drugs, Chinese Herbal (chemistry, therapeutic use)
• Male
• NADPH Oxidases (antagonists & inhibitors)
• Neuroprotective Agents (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (prevention & control)
• Salvia miltiorrhiza (chemistry)
• Triazoles (pharmacology)