Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of Nrf2 expression in ovariectomized rats

Miao, Zhimin; Xia, Xu; Che, Lu; Song, Yufeng

doi:10.1080/01616412.2018.1462879

Cited by 24 publications

(27 citation statements)

References 27 publications

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“…Zhai et al reported that genistein protects against oxidative stress by increasing Nrf‐2 expression through Erk/PKC pathway. Neuroprotective effect of genistein regulates stroke by reducing cerebral ischemia through Nrf2/NQO1 regulation …”

Section: Discussionmentioning

confidence: 99%

Genistein protects against doxorubicin‐induced cardiotoxicity through Nrf‐2/HO‐1 signaling in mice model

Bai

Wang

2019

Environmental Toxicology

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Doxorubicin (DOX)-induced cardiomyopathy is a lethal disease. DOX-induced cardiotoxic effects are attributed towards increased redox status and apoptotic signaling. In this study, we show that genistein offers protection against DOX-induced cardio toxicity in the mice model. DOXmediated increase in serum cardiac troponin and redox markers (ROS, LPO, 4-hydroxynonenalprotein adducts [HNE] levels) was significantly reduced by genistein treatment. Significantly increased TNF-α, IL-6, IL-8 expressions during DOX-induced inflammatory responses were down regulated by genistein treatment. Further, we found that genistein regulated antioxidant response through increased Nrf-2, HO-1, NQO1 protein expressions. In addition, DOX downregulated survival proteins (p-Akt, Bcl-2) with concomitant upregulation in Erk (1/2), Bax and cleaved caspase-3 expressions. The apoptotic activation was significantly downregulated by genistein treatment through suppression of apoptosis. Altogether, these findings show that genistein protects against DOX-induced cardiotoxic effects through activation of Nrf-2/HO-1 signaling. K E Y W O R D S caspase, doxorubicin, genistein, inflammation, Nrf-2

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Section: Discussionmentioning

confidence: 99%

Genistein protects against doxorubicin‐induced cardiotoxicity through Nrf‐2/HO‐1 signaling in mice model

Bai

Wang

2019

Environmental Toxicology

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“…We summarized these studies together in order to provide an overview of this field. Most studies measured total Nrf2 level in the ischemic cortex or brain at 24 h after tMCAO (1–2 h); studies subjects showed Nrf2 upregulation at the mRNA level (Li et al, 2013; Guo et al, 2014) and protein level (up to 2–3 fold higher) (Han et al, 2014; Li et al, 2015; Peng et al, 2015; Shi et al, 2015; Cai et al, 2017; Miao et al, 2018; Shang et al, 2018). Such an increase in Nrf2 protein might begin at 8 h (Cai et al, 2017) and be sustained over 3–14 days (Ding et al, 2015; Lin et al, 2016; Bai et al, 2017; Shang et al, 2018).…”

Section: The Dynamic Regulation Of the Nrf2 Signaling During Cerebralmentioning

confidence: 99%

Critical Role of Nrf2 in Experimental Ischemic Stroke

2019

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Ischemic stroke is one of the leading causes of death and long-term disability worldwide; however, effective clinical approaches are still limited. The transcriptional factor Nrf2 is a master regulator in cellular and organismal defense against endogenous and exogenous stressors by coordinating basal and stress-inducible activation of multiple cytoprotective genes. The Nrf2 network not only tightly controls redox homeostasis but also regulates multiple intermediary metabolic processes. Therefore, targeting Nrf2 has emerged as an attractive therapeutic strategy for the prevention and treatment of CNS diseases including stroke. Here, the current understanding of the Nrf2 regulatory network is critically examined to present evidence for the contribution of Nrf2 pathway in rodent ischemic stroke models. This review outlines the literature for Nrf2 studies in preclinical stroke and focuses on the in vivo evidence for the role of Nrf2 in primary and secondary brain injuries. The dynamic change and functional importance of Nrf2 signaling, as well as Nrf2 targeted intervention, are revealed in permanent, transient, and global cerebral ischemia models. In addition, key considerations, pitfalls, and future potentials for Nrf2 studies in preclinical stroke investigation are discussed.

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“…Apoptosis is the result of a series of cascade activation of nucleases and proteases that involve caspases (Troy et al 2011). A recent previous study found that genistein treatment significantly decreased the cleaved-Caspase-3 expression via promoting Nrf-2 expression and inhibiting ROS production (Miao et al 2018). Wang et al (2014) found that ERK1/2 activation may be involved in the antiapoptotic neuroprotective action of genistein.…”

Section: Discussionmentioning

confidence: 99%

“…Several researchers have found the promising effect of genistein in the alleviation of stroke injuries (Liang et al 2008; Castelló- Ruiz et al 2011; Wang et al 2014;Miao et al 2018). In this study, we explored the effect of genistein treatment on ischemic stroke in ovariectomized rats and found that 10 mg/kg genistein treatment significantly improved the neurological outcomes and decreased the infarct volume in ovariectomized rats subjected to MCAO and reperfusion injury, which was consistent with several previous studies (Wang et al 2014;Miao et al 2018). These results definitely verified the neuroprotective effects of genistein treatment against stroke injury in ovariectomized female animals.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, diet and dietary components have been regarded as important strategies to prevent the stroke or mitigate stroke injury. A plethora of researches showed the promising effect of soy-based genistein, which is one of the predominant isoflavone compounds and is a selective estrogen receptor modulator, in the prevention and mitigation of ischemic stroke-induced damages (Liang et al 2008;Castelló-Ruiz et al 2011;Wang et al 2014;Miao et al 2018). However, the underlying molecular mechanism remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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A preliminary report: genistein attenuates cerebral ischemia injury in ovariectomized rats via regulation of the PI3K-Akt-mTOR pathway

Lu¹,

Liu²,

Gong³

et al. 2019

gpb

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Stroke is a leading cause of disability and death in the worldwide. Therefore, prevention of stroke is critically important. Genistein, a natural phytoestrogen extracted from soybeans, has been found to be a potential neuroprotective agent for stroke prevention. However, the role of genistein and its underlying mechanism in ovariectomized rats has been rarely evaluated. In this study, ovariectomized rats were treated with genistein (10 mg/kg) or vehicle daily for two weeks before they received middle cerebral artery occlusion (MCAO) and reperfusion. Seventy-two hours after reperfusion, the neurological function was evaluated by Garcia test, infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride staining; and neuronal damage and cell apoptosis were detected by Nissl and Tunel staining in the ischemic penumbra, respectively. In addition, Western blotting was used to detect the activity of PI3K-Akt-mTOR signal pathway in the ischemic penumbra in different groups. And we found that genistein treatment in ovariectomized rats significantly improved neurological outcomes, reduced infarct volumes, decreased neuronal damage and cell apoptosis, and increased the activity of PI3K-Akt-mTOR signal pathway. Our findings indicated that treatment genistein could alleviate neuronal apoptosis induced by cerebral ischemia in ovariectomized rats via promoting the activity of PI3K-Akt-mTOR signal pathway, which provides a new molecular mechanism for the neuroprotective effects of genistein against stroke.

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Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of Nrf2 expression in ovariectomized rats

Cited by 24 publications

References 27 publications

Genistein protects against doxorubicin‐induced cardiotoxicity through Nrf‐2/HO‐1 signaling in mice model

Genistein protects against doxorubicin‐induced cardiotoxicity through Nrf‐2/HO‐1 signaling in mice model

Critical Role of Nrf2 in Experimental Ischemic Stroke

A preliminary report: genistein attenuates cerebral ischemia injury in ovariectomized rats via regulation of the PI3K-Akt-mTOR pathway

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