Diosmetin alleviated cerebral ischemia/reperfusion injury in vivo and in vitro by inhibiting oxidative stress via SIRT1/Nrf2 signaling pathway

2021 ◽  
Author(s):  
Zhigang Mei ◽  
Lipeng Du ◽  
Xiaolu Liu ◽  
Xiangyu Chen ◽  
Huan Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Nrf2 Signaling Pathway ◽  
Cerebral Ischemia Reperfusion Injury

Oxidative stress is known to play a pivotal role in the pathogenesis of cerebral ischemia reperfusion (I/R) injury. Accumulating studies have revealed that diosmetin (Dios) could protect against oxidative stress...

scholarly journals Astragali Radix Isoflavones Synergistically Alleviate Cerebral Ischemia and Reperfusion Injury Via Activating Estrogen Receptor-PI3K-Akt Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yong Gu ◽  
Xi Chen ◽  
Shuping Fu ◽  
Wenlan Liu ◽  
Qi Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neuroprotective Effects ◽  
Astragali Radix ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Isoflavones are major neuroprotective components of a medicinal herb Astragali Radix, against cerebral ischemia-reperfusion injury but the mechanisms of neuroprotection remain unclear. Calycosin and formononetin are two major AR isoflavones while daidzein is the metabolite of formononetin after absorption. Herein, we aim to investigate the synergistic neuroprotective effects of those isoflavones of Astragali Radix against cerebral ischemia-reperfusion injury. Calycosin, formononetin and daidzein were organized with different combinations whose effects observed in both in vitro and in vivo experimental models. In the in vitro study, primary cultured neurons were subjected to oxygen-glucose deprivation plus reoxygenation (OGD/RO) or l-glutamate treatment. In the in vivo study, rats were subjected to middle cerebral artery occlusion to induce cerebral ischemia and reperfusion. All three isoflavones pre-treatment alone decreased brain infarct volume and improved neurological deficits in rats, and dose-dependently attenuated neural death induced by l-glutamate treatment and OGD/RO in cultured neurons. Interestingly, the combined formulas of those isoflavones revealed synergistically activated estrogen receptor (estrogen receptors)-PI3K-Akt signaling pathway. Using ER antagonist and phosphatidylinositol 3-kinase (PI3K) inhibitor blocked the neuroprotective effects of those isoflavones. In conclusion, isoflavones could synergistically alleviate cerebral ischemia-reperfusion injury via activating ER-PI3K-Akt pathway.

scholarly journals Silent information regulator 1 ameliorates oxidative stress injury via PGC-1α/PPARγ-Nrf2 pathway after ischemic stroke in rat.

2020 ◽  
Author(s):  
yang zhou ◽  
Li Peng ◽  
Ning Jiang ◽  
Jingxian Wu ◽  
Yixin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background Astrocytes mediate brain defense against oxidative stress-induced injury. Silent information regulator 1 (SIRT1) has anti-oxidative stress effects in many diseases and is highly expressed in astrocytes. However, the neuroprotective effects of SIRT1 on astrocytes after cerebral ischemia/reperfusion injury are unclear. Methods Here, we evaluated the effects of SIRT1 in astrocytes after cerebral ischemia/reperfusion injury using oxygen-glucose deprivation/recovery in astrocytes in vitro and middle cerebral artery occlusion in rats in vivo. Results SIRT1 knockdown reduced cell viability, increased oxidative stress, and decreased peroxisome proliferator activated receptor (PPAR)-γ coactivator (PGC)-1α, PPARγ, nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase (HO)-1, and NAD(P)H:quinone oxidoreductase-1 (NQO1) expression. Moreover, SIRT1 knockdown also suppressed PGC-1α activity, the PGC-1α/PPARγ interaction, and the PPARγ/peroxisome proliferator-response element (PPRE) interaction. Similarly, in our in vivo experiments, SIRT1 overexpression and PGC-1α or PPARγ knockdown reduced PGC-1α, PPARγ, NRF2, HO-1, and NQO1 protein expression and blocked the PGC-1α/PPARγ interaction. SIRT1 overexpression plus PPARγ knockdown inhibited the interaction of PPARγ with PPRE. NRF2 knockdown blocked NRF2 expression and downstream proteins induced by SIRT1 overexpression. Conclusion Overall, our data indicated that SIRT1 directly mediated the PGC-1α/PPARγ pathway in response to focal cerebral ischemia/reperfusion-induced neurological deficit, providing insights into the treatment of focal cerebral ischemia/reperfusion injury.

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