Baicalin can scavenge peroxynitrite and ameliorate endogenous peroxynitrite-mediated neurotoxicity in cerebral ischemia-reperfusion injury

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• 作者：Mingjing Xu ; Xingmiao Chen ; Yong Gu ; Tao Peng ; Dan Yang ; Raymond Chuen-Chuen Chang ; Kwok-Fai So ; Kejian Liu ; Jiangang Shen
• 关键词：ROS ; reactive oxygen species ; SIN-1 ; 3-morpholinosydnonimine ; BBB ; blood brain barrier ; MMPs ; matrix metalloproteinases ; PDC ; peroxynitrite decomposition catalyst ; HX ; hypoxanthine ; XO ; xanthine oxidase ; BMPO ; 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-
• 刊名：Journal of Ethnopharmacology
• 出版年：2013
• 出版时间：28 October, 2013
• 年：2013
• 卷：150
• 期：1
• 页码：116-124
• 全文大小：7534 K

文摘

Ethnopharmacological relevance

Baicalin is one of the principal flavonoids isolated from the dried root of Scutellaria baicalensis Georgi that has long been used to treat ischemic stroke. However, its neuroprotective mechanisms against cerebral ischemia injury are poorly understood.

Aim of the study

To explore the neuroprotective mechanisms of baicalin against cerebral ischemia reperfusion injury.

Material and methods

In chemical systems, we conducted electron paramagnetic resonance (EPR) spin trapping experiments to evaluate the scavenging effects of baicalin on superoxide and nitric oxide, and mass spectrometry (MS) studies on the reaction of baicalin and peroxynitrite. In cellular experiments, we investigated the effects of baicalin against extraneous and endogenous peroxynitrite mediated neurotoxicity in SH-SY5Y cells treated with peroxynitrite donor, synthesized peroxynitrite and exposed to oxygen glucose deprivation and reoxygenation (OGD/RO) in vitro. Moreover, we studied the neuroprotective effects of baicalin by using a rat model of middle cerebral artery occlusion in vivo. FeTMPyP, a peroxynitrite decomposition catalyst, was used as positive control. Cell viability and apoptotic cell death was accessed by MTT assay and TUNEL assay respectively; 3-nitrotyrosine formation and infarction volume were detected by immunostaining experiments and TTC staining respectively.

Results

Baicalin revealed strong antioxidant ability by directly scavenging superoxide and reacting with peroxynitrite. Baicalin protected the neuronal cells from extraneous and endogenous peroxynitrite-induced neurotoxicity. In ischemia-reperfused brains, baicalin inhibited the formation of 3-nitrotyrosine, reduced infarct size and attenuated apoptotic cell death, whose effects were similar to FeTMPyP.

Conclusions

Baicalin can directly scavenge peroxynitrite and the peroxynitrite-scavenging ability contributes to its neuroprotective mechanisms against cerebral ischemia reperfusion injury.