Neuroprotection by the Traditional Chinese Medicine, Tao‐Hong‐Si‐Wu‐Tang, against Middle Cerebral Artery Occlusion‐Induced Cerebral Ischemia in Rats

Abstract

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)‐1 α , 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 μ g 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‐1 α 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.