Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice.
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.
1. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi'an, China; ; 4. Dr Shiquan Wang and Dr Haidong Wei equally contributed to this work.
Shiquan
S
Wang
2. Department of Anesthesiology, the Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, China; ; 4. Dr Shiquan Wang and Dr Haidong Wei equally contributed to this work.
Haidong
H
Wei
3. Department of Psychosomatic Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China;
Min
M
Cai
1. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi'an, China;
Yan
Y
Lu
1. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi'an, China;
Wugang
W
Hou
1. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi'an, China;
Qianzi
Q
Yang
1. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi'an, China;
Hailong
H
Dong
1. Department of Anesthesiology, Xijing Hospital, Forth Military Medical University, Xi'an, China;
Lize
L
Xiong
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019833:Genistein / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D048789:Phytoestrogens / Q000627:therapeutic use*; D017698:Postmenopause; D020521:Stroke / Q000188:drug therapy*; D015854:Up-Regulation / Q000187:drug effects
D002070:Butadienes; D018696:Neuroprotective Agents; D009570:Nitriles; D048789:Phytoestrogens; C113580:U 0126; D019833:Genistein; D048049:Extracellular Signal-Regulated MAP Kinases
cerebral ischemia; extracellular signal-regulated protein kinase; genistein; phytoestrogen; postmenopausal stroke.