Lee E-Jian, Chen Hung-Yi, Hung Yu-Chang, Chen Tsung-Ying, Lee Ming-Yang, Yu Shu-Ching, Chen Ying-Hsin, Chuang I-Chuan, Wu Tian-Shung
Department of Surgery, Neurophysiology Laboratory, Neurosurgical Service, National Cheng Kung University Medical Center and Medical School, Tainan, Taiwan.
Exp Neurol. 2009 May;217(1):74-83. doi: 10.1016/j.expneurol.2009.01.019. Epub 2009 Feb 5.
Cinnamophilin (CINN, (8R, 8'S)-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan) protects against ischemic stroke in mice. While some anti-oxidative effects of CINN have been characterized, its therapeutic window and molecular basis for neuroprotection remain unclear. We evaluated antioxidant and anti-inflammatory properties and therapeutic window of CINN against brain ischemia using a panel of in vitro and in vivo assays. Data from lipid peroxidation and radical scavenging assays showed that CINN was a robust antioxidant and radical scavenger. CINN effectively inhibited the production of tumor necrosis factor alpha (TNF-alpha), nitrite/nitrate, interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 and BV2 cells (P<0.05, respectively). Relative to controls, CINN, administrated at 80 mg/kg, 2, 4, or 6 h postinsult, but not 12 h, significantly reduced brain infarction by 34-43% (P<0.05) and improved neurobehavioral outcome (P<0.05) following transient focal cerebral ischemia in rats. CINN (10-30 microM) also significantly reduced oxygen-glucose deprivation-induced neuronal damage (P<0.05) in rat organotypic hippocampal slices, even when it was administrated 2, 4, or 6 h postinsult. Together, CINN protects against ischemic brain damage with a therapeutic window up to 6 h in vivo and in vitro, which may, at least in part, be attributed by its direct antioxidant and anti-inflammatory effects.
肉桂脂素（CINN，(8R, 8'S)-4, 4'-二羟基-3, 3'-二甲氧基-7-氧代-8, 8'-新木脂素）可保护小鼠免受缺血性中风的影响。虽然已对CINN的一些抗氧化作用进行了表征，但其治疗窗和神经保护的分子基础仍不清楚。我们使用一系列体外和体内试验评估了CINN对脑缺血的抗氧化和抗炎特性以及治疗窗。脂质过氧化和自由基清除试验的数据表明，CINN是一种强大的抗氧化剂和自由基清除剂。CINN有效抑制脂多糖（LPS）刺激的RAW 264.7和BV2细胞中肿瘤坏死因子α（TNF-α）、亚硝酸盐/硝酸盐、白细胞介素-6（IL-6）的产生（分别为P<0.05）。相对于对照组，在大鼠短暂性局灶性脑缺血后，于损伤后2、4或6小时而非12小时给予80 mg/kg的CINN，可显著减少脑梗死34-43%（P<0.05）并改善神经行为结果（P<0.05）。即使在损伤后2、4或6小时给予，CINN（10-30 microM）也能显著减少大鼠器官型海马切片中氧-葡萄糖剥夺诱导的神经元损伤（P<0.05）。总之，CINN在体内和体外均可保护免受缺血性脑损伤，其治疗窗长达6小时，这可能至少部分归因于其直接的抗氧化和抗炎作用。
