Brain Medical Center, Hangzhou, Zhejiang 310003, China , Department of Neurology, First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, China.
Am J Chin Med. 2013;41(6):1329-41. doi: 10.1142/S0192415X13500894.
Extracts of Ginkgo biloba have been used in traditional medicines for centuries, and have potential for clinical applications in cerebral ischemia/reperfusion injury. However, standardized extracts have proven protective only as pre-treatments, and the major mechanisms of action remain unclear. We explored the potential of the novel extract EGB1212, which meets the United States Pharmacopeia (USP) 31 standardization criteria for pharmaceutical use, as a post-treatment after global cerebral ischemia/reperfusion (GCI/R) injury in a rat model. The pre-treated group was administered EGB1212 for 7 d prior to common carotid artery occlusion (i.e., ischemia, for 20 min). Post-treated rats received the same but starting 2 h after ischemia and continuing for 7 d. Seven days after GCI/R, brains of each group were processed for H&E staining of hippocampal CA1 neurons. Remaining rats underwent the Morris water maze and Y-maze tests of spatial learning and memory, beginning eight days after reperfusion. To assess hippocampal autophagy, light chain (LC)-3-I/LC3-II and Akt/pAkt were determined via a Western blot of rat hippocampi harvested 12, 24, or 72 h after reperfusion. EGB1212 pre- and post-treatments both improved neuronal survival and spatial learning and memory functions. Pre-treatment effectively reduced LC3-II levels and post-treatment resulted in significantly elevated pAkt levels. We conclude that EGB1212 exerted significant neuroprotection in GCI/R in both preventative and post-treatment settings. This extract shows great potential for clinical applications.
银杏叶提取物在传统医学中已经使用了几个世纪，并且在脑缺血/再灌注损伤的临床应用中具有潜力。然而，标准化提取物仅作为预处理时被证明具有保护作用，其主要作用机制仍不清楚。我们研究了新型提取物 EGB1212 的潜力，该提取物符合美国药典（USP）31 用于药物的标准化标准，作为一种在大鼠模型中的全脑缺血/再灌注（GCI/R）损伤后的治疗方法。预处理组在颈总动脉闭塞（即缺血，20 分钟）前 7 天给予 EGB1212。后处理组在缺血后 2 小时开始并持续 7 天给予相同的药物。GCI/R 后 7 天，每组大鼠的大脑均进行海马 CA1 神经元的 H&E 染色。其余大鼠在再灌注后 8 天开始进行 Morris 水迷宫和 Y 迷宫空间学习和记忆测试。为了评估海马自噬，通过 Western blot 检测大鼠海马中 LC3-I/LC3-II 和 Akt/pAkt 的表达，分别在再灌注后 12、24 或 72 小时采集。EGB1212 的预处理和后处理均改善了神经元的存活和空间学习记忆功能。预处理有效降低了 LC3-II 水平，后处理导致 pAkt 水平显著升高。我们得出结论，EGB1212 在预防和后处理两种情况下均对 GCI/R 发挥了显著的神经保护作用。这种提取物显示出了很大的临床应用潜力。
