Neuroprotection by the Traditional Chinese Medicine, Tao-Hong-Si-Wu-Tang,
against Middle Cerebral Artery Occlusion-Induced Cerebral Ischemia in Rats
Chih-Jen Wu, Jui-Tai Chen, Ting-Lin Yen, Thanasekaran Jayakumar,
Duen-Suey Chou, George Hsiao, and Joen-Rong Sheu
Tao-Hong-Si-Wu-Tang (THSWT) is a famous traditional Chinese medicine (TMC). In the present study, oral administration of THSWT (0.7 and 1.4 g kg-1 day-1) for 14 days before MCAO dose-dependently attenuated focal cerebral ischemia in rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor (HIF)-1α, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and active caspase-3 expressions in ischemic regions. These expressions were obviously inhibited by 0.7 g kg-1 day-1 THSWT treatment. In addition, THSWT inhibited platelet aggregation stimulated by collagen in washed platelets. In an in vivo study, THSWT (16 g kg-1) significantly prolonged platelet plug formation in mice. However, THSWT (20 and 40 μg mL-1) did not significantly reduce the electron spin resonance (ESR) signal intensity of hydroxyl radical (OH•) formation. In conclusion, the most important findings of this study demonstrate for the first time that THSWT possesses potent neuroprotective activity against MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1α and TNF-α activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and platelet activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury.
Copyright © 2011 Chih-Jen Wu et al. This is an open access article
distributed under the Creative Commons Attribution License.
2. Materials and methods
1. MCAO-Induced Transient Focal Cerebral Ischemia in Rats
2. Neurobehavioral Test
3. Platelet Aggregation
4. Fluorescein Sodium-Induced Platelet Thrombi in Mesenteric Microvessels of Mice
5. Electron Spin Resonance (ESR) Spectrometry
6. Data Analysis
1. Reduction of MCAO-Induced Focal Cerebral Ischemia by THSWT in Rats
2. Inhibition of HIF-1α, iNOS, TNF-α, and Active Caspase-3 Expressions by THSWT in Ischemic Cerebral Tissues
3. Effects of THSWT on Platelet Aggregation In Vitro and Thrombus Formation in Microvessels of Fluorescein Sodium-Pretreated Mice In Vivo
4. Inhibition of Hydroxyl Radical (OH•) Formation by THSWT in ESR Spectrometry
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