PMID- 30098550 OWN - NLM STAT- MEDLINE DCOM- 20190122 LR - 20211204 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 107 DP - 2018 Nov TI - Standardized Ginkgo biloba extract EGb 761(R) attenuates early brain injury following subarachnoid hemorrhage via suppressing neuronal apoptosis through the activation of Akt signaling. PG - 329-337 LID - S0753-3322(18)33130-5 [pii] LID - 10.1016/j.biopha.2018.08.012 [doi] AB - BACKGROUND: Early brain injury (EBI) plays a critical role in determining the outcome of subarachnoid hemorrhage (SAH). The present study was designed to investigate the role of EGb 761, a standardized extract of Ginkgo biloba, in SAH-induced EBI and to explore its potential mechanism of action. METHOD: A rat SAH model was established by the endovascular perforation process. Doses of 10, 50 and 100 mg/kg EGb 761 were injected intraperitoneally 2 h after SAH was induced. Mortality, SAH grade, neurological score and brain water content were measured 24 h after SAH was induced. A Western blot assay was performed to assess the expression of the apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3, Akt and phosphorylated Akt (p-Akt). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and neuronal nuclei (NeuN) double immunofluorescence staining were used to detect apoptotic neurons. RESULTS: Animals suffered from serious neurological deficits and increased brain water content after induction of SAH. Rats treated with EGb 761 experienced dose-dependent attenuation of neurological dysfunction and decreased brain water content. In addition, EGb 761 significantly activated Akt signaling accompanied by increased Bcl-2 levels and decreased expression of Bax and cleaved caspase-3. Moreover, EGb 761 decreased the number of TUNEL/NeuN-positive cells in a dose-dependent manner. However, all the beneficial effects of EGb 761 for SAH were abolished by the Akt inhibitor MK2206. CONCLUSION: Our results indicated that EGb 761 could ameliorate SAH-induced EBI and that the neuroprotective effects of EGb 761 against SAH were exerted via suppression of neuronal apoptosis through activation of the Akt pathway. CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved. FAU - Yu, Ting AU - Yu T AD - Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. FAU - Fan, Yunren AU - Fan Y AD - Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. FAU - Xu, Yunfeng AU - Xu Y AD - Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. FAU - Xu, Liangdie AU - Xu L AD - Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. FAU - Xu, Guangda AU - Xu G AD - Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. FAU - Cao, Fangchuan AU - Cao F AD - Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. FAU - Jiang, Hailong AU - Jiang H AD - Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. Electronic address: nsjianghailong@163.com. LA - eng PT - Journal Article DEP - 20180808 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Neuroprotective Agents) RN - 0 (Plant Extracts) RN - 0 (bcl-2-Associated X Protein) RN - 19FUJ2C58T (Ginkgo biloba extract) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - *Apoptosis/drug effects MH - Brain Edema/complications/drug therapy/pathology/physiopathology MH - Brain Injuries/*drug therapy/*etiology/pathology/physiopathology MH - Caspase 3/metabolism MH - Ginkgo biloba MH - Male MH - Models, Biological MH - Neurons/drug effects/enzymology/*pathology MH - Neuroprotection/drug effects MH - Neuroprotective Agents/pharmacology/therapeutic use MH - Plant Extracts/pharmacology/*therapeutic use MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects MH - Subarachnoid Hemorrhage/*complications MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Akt OT - Apoptosis OT - Early brain injury OT - Subarachnoid hemorrhage EDAT- 2018/08/12 06:00 MHDA- 2019/01/23 06:00 CRDT- 2018/08/12 06:00 PHST- 2018/05/09 00:00 [received] PHST- 2018/08/03 00:00 [revised] PHST- 2018/08/03 00:00 [accepted] PHST- 2018/08/12 06:00 [pubmed] PHST- 2019/01/23 06:00 [medline] PHST- 2018/08/12 06:00 [entrez] AID - S0753-3322(18)33130-5 [pii] AID - 10.1016/j.biopha.2018.08.012 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Nov;107:329-337. doi: 10.1016/j.biopha.2018.08.012. Epub 2018 Aug 8.