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Planta Med 2015; 81(15): 1361-1369
DOI: 10.1055/s-0035-1557774
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Salviaolate Protects Rat Brain from Ischemia-Reperfusion Injury through Inhibition of NADPH Oxidase

Zheng Lou   *
1   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Kai-Di Ren   *
1   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Bin Tan
1   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Jing-Jie Peng
1   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
2   Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China
,
Xian Ren
1   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Zhong-Bao Yang
1   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Bin Liu
1   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
,
Jie Yang
3   Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
,
Qi-Lin Ma
4   Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China
,
Xiu-Ju Luo
2   Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China
,
Jun Peng
1   Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China
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Publikationsverlauf

received 29. Januar 2015
revised 28. Mai 2015

accepted 15. Juni 2015

Publikationsdatum:
07. August 2015 (online)

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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.

Key words

Salvia miltiorrhiza - Lamiaceae - salviaolate - magnesium lithospermate B - Danshen - ischemia/reperfusion - NADPH oxidase

* These authors contributed equally to this work.


Supporting Information

 

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