Taraxasterol protects hippocampal neurons from oxygen-glucose deprivation-induced injury through activation of Nrf2 signalling pathway

Abstract

Cerebral ischemia/reperfusion (I/R) injury is a brain injury following ischaemic stroke that is associated with oxidative stress. Taraxasterol, a natural product, has been shown to have anti-oxidative and neuro-protective effects. However, the role of taraxasterol in cerebral I/R injury remains unknown. Primary hippocampal neurons were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to induce cerebral I/R injury in vitro. Cell viability of hippocampal neurons was measured CCK-8 assay. Reactive oxygen species (ROS) production and MDA generation were measured to reflect oxidative stress. Western blotting was performed to evaluate the expressions of bax, bcl-2, NF-E2-related factor 2 (Nrf2), haem oxygenase (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1) and GPx-3. Caspase-3 activity was measured to assess cell apoptosis. Hippocampal neurons were treated with ML385 to inhibit Nrf2 signalling pathway. Our results showed that taraxasterol improved OGD/R-caused decrease in cell viability of hippocampal neurons. In addition, taraxasterol significantly suppressed ROS production and MDA generation in OGD/R-induced hippocampal neurons. Taraxasterol resulted in a significant decrease in caspase-3 activity and bcl-2 expression, as well as increase in bax expression. Furthermore, taraxasterol induced the Nrf2 nuclear accumulation and expressions of HO-1, NQO-1 and GPx-3 in OGD/R-induced hippocampal neurons. Notably, inhibition of Nrf2 signalling reversed the protective effects of taraxasterol on OGD/R-induced hippocampal neurons injury. In conclusion, these findings indicated that taraxasterol protected hippocampal neurons from OGD/R-induced oxidative stress and cell apoptosis via regulating the Nrf2 signalling pathway.

RETRACTED ARTICLE: Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury

“…Cerebral ischemia/reperfusion injury (CI/RI) is a kind of brain injury followed by ischemic stroke [1]. The most characteristic feature of cerebral I/R is initial transient cerebral ischemia following reperfusion [2].…”

Resveratrol attenuates methamphetamine‐induced memory impairment via inhibition of oxidative stress and apoptosis in mice

“…Compared with the healthy control, MDA levels of METH abusers were significantly increased and SOD activities were decreased (Huang et al, 2013). cytoprotective genes, such as HO-1, and GCSc-γ (He et al, 2020;Taguchi et al, 2020), and Keap1, a repressor protein that binds to Nrf2 and promotes its degradation by the ubiquitin-proteasome pathway (Kansanen et al, 2013). Nrf2 stores in the cytoplasm as an inactive form via binding to Keap1 and the sensitive amino acid residues on Keap1 could combine with some stimulus, which will cause the change of the conformation and lose the ability to bind to Nrf2, then, Nrf2 can be activated after entering into the nucleus and regulate the transcription of target genes (He et al, 2020;Taguchi et al, 2020).…”

“…Nrf2 is an essential redox‐regulated transcription factor that can regulate the transcription of cytoprotective genes, such as HO‐1, GCSc‐γ, and SOD during oxidative stress in the brain, Nrf2 stores in the cytoplasm as an inactive form via binding to Keap1, the conformational change of Keap1 could facilitate the dissociation of Nrf2 from Nrf2‐Keap1 complex, which allows Nrf2 to translocate into the nucleus (He et al., 2020; Taguchi et al., 2020). So the effect of resveratrol on the expressions of related proteins in the Keap1‐Nrf2 pathway was shown in Figure 5.…”

“…The key signaling proteins within the pathway are the Nrf2 that binds together with small Maf proteins to the antioxidant response element (ARE) in the transcriptional regulatory regions of cytoprotective genes, such as HO‐1, and GCSc‐γ (He et al., 2020; Taguchi et al., 2020), and Keap1, a repressor protein that binds to Nrf2 and promotes its degradation by the ubiquitin‐proteasome pathway (Kansanen et al., 2013). Nrf2 stores in the cytoplasm as an inactive form via binding to Keap1 and the sensitive amino acid residues on Keap1 could combine with some stimulus, which will cause the change of the conformation and lose the ability to bind to Nrf2, then, Nrf2 can be activated after entering into the nucleus and regulate the transcription of target genes (He et al., 2020; Taguchi et al., 2020). Several studies documented that Nrf2‐knockout mice exhibit greater METH‐initiated loss of dopaminergic terminals and postnatal neurodevelopmental deficits (Ramkissoon & Wells, 2013, 2015).…”

The Effect of Angelica sinensis Polysaccharide on Neuronal Apoptosis in Cerebral Ischemia-Reperfusion Injury via PI3K/AKT Pathway

“…Cerebral ischemia-reperfusion injury (CIRI) is a brain injury after ischemic stroke [1]. The most typical feature of CIRI is transient ischemia following reperfusion [2].…”