1. Academic Validation
  2. Isorhamnetin Alleviates High Glucose-Aggravated Inflammatory Response and Apoptosis in Oxygen-Glucose Deprivation and Reoxygenation-Induced HT22 Hippocampal Neurons Through Akt/SIRT1/Nrf2/HO-1 Signaling Pathway

Isorhamnetin Alleviates High Glucose-Aggravated Inflammatory Response and Apoptosis in Oxygen-Glucose Deprivation and Reoxygenation-Induced HT22 Hippocampal Neurons Through Akt/SIRT1/Nrf2/HO-1 Signaling Pathway

  • Inflammation. 2021 Oct;44(5):1993-2005. doi: 10.1007/s10753-021-01476-1.
Yuqin Wu 1 Lin Fan 1 Yun Wang 1 Jing Ding 1 Rongfu Wang 2
Affiliations

Affiliations

  • 1 Department of Neurology, Jiangsu Taizhou People's Hospital, No. 366, Taihu Road, Gaoxin District, Taizhou, 225300, Jiangsu, China.
  • 2 Department of Neurology, Jiangsu Taizhou People's Hospital, No. 366, Taihu Road, Gaoxin District, Taizhou, 225300, Jiangsu, China. RongfuWang2020@163.com.
Abstract

This study is aimed at exploring the potential of isorhamnetin in protection against diabetes-exacerbated ischemia/reperfusion-induced brain injury and elucidating its action mechanism. After establishment of the model of high glucose (HG)-aggravated oxygen-glucose deprivation and reoxygenation (OGD/R), HT22 cell viability was detected by CCK-8. Lactate Dehydrogenase (LDH) activity, casapase-3 activity, and oxidative stress-related markers in HT22 cells were detected by corresponding commercial kits. The Apoptosis of HG-treated HT22 cells following OGD/R was observed with TUNEL staining. The level of pro-inflammatory cytokines was examined by ELISA. The expression of Akt/SIRT1/Nrf2/HO-1 signaling-related proteins was assayed by Western blot. The results showed that HG noticeably worsened the OGD/R-induced Apoptosis of HT22 cells. Isorhamnetin relieved the HG-aggravated OGD/R-induced Apoptosis, inflammatory response, and oxidative stress of HT22 cells. Isorhamnetin alleviated the HG-aggravated OGD/R injury in HT22 cells through Akt/SIRT1/Nrf2/HO-1 signaling pathway. Meanwhile, treatment with Akt Inhibitor LY294002 reversed the protective effects of isorhamnetin against HG-aggravated OGD/R injury in HT22 cells. In a conclusion, Isorhamnetin alleviates HG-aggravated OGD/R in HT22 hippocampal neurons through Akt/SIRT1/Nrf2/HO-1 signaling pathway.

Keywords

Akt/SIRT1/Nrf2/HO-1; OGD/R; high glucose; hypoxia and reoxygenation; isorhamnetin.

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