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Int J Biol Sci 2014; 10(4):457-465. doi:10.7150/ijbs.7562

Research Paper

Genistein Attenuates Brain Damage induced by Transient Cerebral Ischemia Through Up-regulation of ERK Activity in Ovariectomized Mice

Shiquan Wang1, 4, Haidong Wei2, 4, Min Cai3, Yan Lu1, Wugang Hou1, Qianzi Yang1, Hailong Dong1✉, Lize Xiong1✉

1. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi'an, China;
2. Department of Anesthesiology, the Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, China;
3. Department of Psychosomatic Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China;
4. Dr Shiquan Wang and Dr Haidong Wei equally contributed to this work.


Stroke has severe consequences in postmenopausal women. As replacement therapy of estrogen have various adverse effects and the undermined outcomes. Genistein, a natural phytoestrogen, has been suggested to be a potential neuroprotective agent for such stroke patients. However, the role of genistein and its underlying mechanism in ovariectomized mice has not yet been evaluated. In the present study, ovariectomized mice were treated with genistein (10 mg/kg) or vehicle daily for two weeks before developing transient cerebral ischemia (middle cerebral artery occlusion). The neurological manifestation was evaluated, and infarct volumes were demonstrated by 2,3,5-triphenyltetrazolium chloride staining at 24 h after reperfusion. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) was detected by Western blotting and immunofluorescence staining, and cellular apoptosis was evaluated in the ischemic penumbra. We found that treatment with genistein reduced infarct volumes, improved neurological outcomes and attenuated cellular apoptosis at 24 h after reperfusion. ERK1/2 showed increased phosphorylation by genistein treatment after reperfusion, and an ERK1/2 inhibitor U0126 abolished this protective effect of genistein in terms of infarct volumes, neurological scores and cellular apoptosis. Our findings indicate that treatment with genistein can reduce the severity of subsequent stroke episodes, and that this beneficial function is associated with ERK activation.

Keywords: cerebral ischemia, extracellular signal-regulated protein kinase, genistein, phytoestrogen, postmenopausal stroke.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
How to cite this article:
Wang S, Wei H, Cai M, Lu Y, Hou W, Yang Q, Dong H, Xiong L. Genistein Attenuates Brain Damage induced by Transient Cerebral Ischemia Through Up-regulation of ERK Activity in Ovariectomized Mice. Int J Biol Sci 2014; 10(4):457-465. doi:10.7150/ijbs.7562. Available from