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| 1 | Scutellarin protects oxygen/glucose-deprived astrocytes and reduces focal cerebral ischemic injury显示文摘Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti-inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxidative effects and has been used to treat cardiovascular and cerebrovascular diseases in China. However, the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia remain unclear. The interaction between scutellarin and nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) was assessed by molecular docking study, which showed that scutellarin selectively binds to NOX2 with high affinity. Cultures of primary astrocytes isolated from the cerebral cortex of neonatal Sprague-Dawley rats were pretreated with 2, 10 or 50 μM scutellarin for 30 minutes. The astrocytes were then subjected to oxygen/glucose deprivation by incubation for 2 hours in glucose-free Dulbecco's modified Eagle's medium in a 95% N2/5% CO_2 incubator, followed by simulated reperfusion for 22 hours. Cell viability was assessed by cell counting kit-8 assay. Expression levels of NOX2, connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen species were measured spectrophotometrically. Pretreatment with 10 or 50 μM scutellarin substantially increased viability, reduced the expression of NOX2 and caspase-3, increased the expression of connexin 43, and diminished the levels of reactive oxygen species in astrocytes subjected to ischemia-reperfusion. We also assessed the effects of scutellarin in vivo in the rat transient middle cerebral artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The Bederson scale was used to assess neurological deficit, and 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct size. Western blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue. Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine(8-OHd G), 4-hydroxy-2-nonenal(4-HNE) and 3-nitrotyrosin(3-NT) in brain tissue. Immunofluorescence double staining was used to determine the co-expression of caspase-3 and Neu N. Pretreatment with scutellarin improved the neurological function of rats with focal cerebral ischemia, reduced infarct size, diminished the expression of NOX2, reduced levels of 8-OHd G, 4-HNE and 3-NT, and reduced the number of cells co-expressing caspase-3 and Neu N in the injured brain tissue. Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin substantially increased connexin 43 expression in vivo and in vitro. Collectively, our findings suggest that scutellarin protects against ischemic injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43, decreasing oxidative damage, and reducing apoptotic cell death. | Jing-Bo Sun Yan Li Ye-Feng Cai Yan Huang Shu Liu Patrick KK Yeung Min-Zhen Deng Guang-Shun Sun Prince LM Zilundu Qian-Sheng Hu Rui-Xin An Li-Hua Zhou Li-Xin Wang Xiao Cheng | 2018 | Neural Regeneration Research2018，13，8： | 16 |
| 2 | Inflammation, anti-inflammatory agents and Alzheimer disease: the last 12 years 显示文摘 | Patrick LM Joseph R Edith GM | 2006 | J Alzheimers Dis2006，9，： | 1 |
| 3 | Enhanced islet expansion by beta cell proliferation in young diabetes prone rats fed a protective diet 显示文摘 | Wang GS Kauri LM Patrick C | 2010 | J Cell Physiol2010，224，2： | 1 |
| 4 | Enhanced islet expansion by beta-cell proliferation in young diabetes-prone rats fed a pro- tective diet显示文摘 | Wang GS Kauri LM Patrick C | 2010 | J Cell Physiol2010，224，2： | 1 |
| 5 | Development of a guinea pig model of chorioamnionitis and fetal brain injury显示文摘 | Patrick LA Gaudet LM Farley AE | 2004 | Am J Obstet Gynecol2004，191，4： | 1 |
| 6 | Pharmacology of Neuronal nictonic acetylcholine receptors subtypes显示文摘 | Colquhoun LM Patrick J W | 1997 | Adv Pharmacol1997，39，： | 1 |
| 7 | Mechanical production of madibular fractures: strain-gauge measurement of impacts to the chin显示文摘 | Patrick LM | 1963 | J Dent Res1963，43，： | 1 |
| 8 | Poor intraoperative blood glucose control is associated with a worsened hospital outcome after cardiac surgery in diabetic patients显示文摘 | Alexandre O Patrick L Yannick LM | 2005 | Anesthesiology2005，103，4： | 1 |
| 9 | Cadaver windshield impact reseach显示文摘 | | 1966 | Plast Reconstr Surg1966，37，： | 1 |
| 10 | Cadaver windshield impact reseach显示文摘 | | 1966 | Plast Reconstr Surg1966，37，： | 1 |
| 11 | Development of a guinea pig model of chofioanmionltis and fetal brain injury显示文摘 | Patrick LA Gaudet LM Farley AE | 2004 | Am J Obstet Gynecol2004，191，： | 1 |
| 12 | 2 Identification of SATB2 as the cleft palate gene on 2q32-q33 显示文摘 | Fitz Patrick DR Carr LM McLaren L | 2003 | Human Molecular Genetlcs2003，12，19： | 1 |
| 13 | Immunohistochemical study of nuclear changes associated with male germ cell death and spermiogenesis显示文摘 | McClusky LM Patrick S Barnhoorn IE | | 0，，04： | 1 |
| 14 | The inflammatory response system of bra in:implications for therapy of Alzheimer and other neurodegenerative disease显示文摘 | Edith GM | 1995 | Brain Res Rev1995，21，： | 1 |
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