Neuroprotective effects of Tanshinone IIA on permanent focal cerebral ischemia in mice.
The objective of this study was to evaluate whether Tanshinone IIA (TSA) was neuroprotective in permanent focal cerebral ischemia and to determine the possible mechanisms of its neuroprotection. Mice were subjected to permanent middle cerebral artery occlusion. The neuroprotection of TSA was investigated with respect to neurological deficit scores and infarct volume. Biochemical analyses for malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in serum, and nitric oxide (NO) content and the inducible nitric oxide synthase (iNOS) activity in brain tissue were performed at 24 h after ischemia. Immunohistochemistry was used to measure the expression of iNOS. In vitro, the effects of TSA were tested in the cultured astrocytes exposed to hydrogen dioxide (H2O2). TSA (5, 10 and 20 mg/kg, i.p.) significantly reduced the infarct volume and improve neurological deficit. TSA also significantly increased the activity of SOD after 24 h of ischemia and decreased the MDA level, NO content, and iNOS expression. In vitro, the translocation of NF-kappaB was inhibited by TSA and the survival rate of astrocytes was markedly increased and the NO production was decreased. In conclusion, these results illustrated that TSA protected the brain from ischemic injury by suppressing the oxidative stress and the radical-mediated inflammatory insult.
Dong
Kenan
K
Institute of Chinese Herbal Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Xu
Wei
W
Yang
Jun
J
Qiao
Hongxiang
H
Wu
Limao
L
D045784:Abietanes; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000503:physiopathology; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D006861:Hydrogen Peroxide / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010616:Phenanthrenes / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010616:Phenanthrenes; C021751:tanshinone; D009569:Nitric Oxide; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase