EGB1212 post-treatment ameliorates hippocampal CA1 neuronal death and memory impairment induced by transient global cerebral ischemia/reperfusion.
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.
Brain Medical Center, Hangzhou, Zhejiang 310003, China , Department of Neurology, First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, China.
Bo
B
Yin
Hui
H
Liang
Yigang
Y
Chen
Ketan
K
Chu
Li
L
Huang
Ling
L
Fang
Erik
E
Matro
Weijian
W
Jiang
Benyan
B
Luo
D020236:Amnesia, Transient Global / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001927:Brain Diseases / Q000150:complications*; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D020441:Ginkgo biloba; D002546:Ischemic Attack, Transient / Q000150:complications*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D013997:Time Factors; D000096983:Ginkgo Extract
D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; C000589197:Ginkgo biloba extract 1212; D000096983:Ginkgo Extract; C526109:Anxa3 protein, rat