title: Formononetin mediates neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway.
abstract: Isoflavone formononetin is a typical phytoestrogen isolated from Chinese medical herb red clover. It has been reported that estrogens have neuroprotective properties, and dietary intake of phytoestrogens could reduce stroke injury in cerebral ischemia/reperfusion (I/R) animal models. In the present research, we sought to investigate the molecular mechanisms underlying the neuroprotective effects of formononetin on I/R rats. Male Sprague-Dawley rats were subjected to a 2 h period of right middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. Then neurological deficits and brain edema were evaluated. To provide insight into the functions of phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK (mitogen-activated protein kinase) signaling pathway in formononetin-induced neuroprotection, the expression of ER-α, Bax, Bcl-2, p-Akt (phosphorylated protein kinase B), and p-ERK1/2 (phosphorylated extracellular signal-regulated kinases 1/2) was determined by qPCR or Western blot assay. Consequently, we found that formononetin has significantly reduced the infarcted volume and the brain water content, and improved the neurological deficit. Formononetin also exhibited an upregulation in ER-α and p-Akt, a downregulation in the ratio of Bax/Bcl-2. However, formononetin had little effect on p-ERK1/2 proteins expression. Taken together, formononetin has shown neuroprotective effects in cerebral I/R rats, and the molecular mechanisms may correlate with the downregulation of the Bax/Bcl-2 ratio and the activation of PI3K/Akt signaling pathway.
authors.affiliation: Department of Emergency, Western Hospital, First Affiliated Hospital of Guangxi Medical University, Nanning 530007, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liang
authors.affiliation: Department of Emergency, Western Hospital, First Affiliated Hospital of Guangxi Medical University, Nanning 530007, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Physiology, Guilin Medical University, Guilin 541004, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Emergency, Western Hospital, First Affiliated Hospital of Guangxi Medical University, Nanning 530007, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Western Hospital, First Affiliated Hospital of Guangxi Medical University, Nanning 530007, China. Electronic address: gxxiaozm@163.com.
authors.forename: Chaoqian
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D007529:Isoflavones; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C007768:formononetin; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: Bax; Bcl-2; Cerebral ischemia/reperfusion; ER-α; Formononetin; PI3K/Akt pathway