Pterostilbene Attenuates Astrocytic Inflammation and Neuronal Oxidative Injury After Ischemia-Reperfusion by Inhibiting NF-κB Phosphorylation

Abstract

Astrocyte-mediated inflammation and oxidative stress elicit cerebral ischemia-reperfusion (IR) injury after stroke. Nuclear factor (NF)-κB activates astrocytes and generates pro-inflammatory factors. The purpose of the present study is to elucidate the effect of pterostilbene (PTE, a natural stilbene) on astrocytic inflammation and neuronal oxidative injury following cerebral ischemia-reperfusion injury. A middle cerebral artery occlusion-reperfusion (MCAO/R) mouse model and HT22/U251 co-culture model subjected to oxygen-glucose deprivation and re-introduction (OGD/R) were employed, with or without PTE treatment. The data showed that PTE delivery immediately after reperfusion, at 1 h after occlusion, decreased infarct volume, brain edema, and neuronal apoptosis and improved long-term neurological function. PTE decreased oxidation (i.e., production of reactive oxygen species, malondialdehyde) and inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and increased anti-oxidative enzyme activities (i.e., of superoxide dismutase, glutathione peroxidase), by inhibiting phosphorylation and nuclear translocation of NF-κB. In conclusion, PTE attenuated astrocyte-mediated inflammation and oxidative injury following IR via NF-κB inhibition. Overall, PTE is a promising neuroprotective agent.

Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol

“…This protective effect may be at least partly related to the inhibition of oxidative stress and apoptosis of neurons in the penumbra of the cortex. Another article showed the same conclusion by studying this model; however, the mechanism was pterostilbene's reduction of astrocyte-mediated inflammation and oxidative damage after ischemia reperfusion by inhibiting NF-κB phosphorylation and nuclear translocation [70].…”

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling

“…SH-SY5Y human neuroblastoma cell line and BV-2 mouse microglia cell line were obtained from the Neurological Lab of Tangdu Hospital. [18]. Culture media were changed every 2 days.…”

“…Finally, although many mysteries exist regarding the effects and mechanisms of the microglia in neurological diseases, it shows the microglia as a promising future to treat neurological disorders, especially to cure neurodegeneration. Increasing evidence has proved that PTE has regulatory effects on neurological disorders, especially neurodegeneration and stroke [18]. However, the modulatory roles of PTE in microglial activation and following injury have not been given enough attention.…”

“…Intriguingly, in the CNS, PTE are able to penetrate the blood brain barrier (BBB) and to modulate neural activity [22], which may exert protection against degenerative disorders [21], hyperprolactinemia [23], and stroke [18,24,25]. The biological effects of PTE on neural cells involve the regulation of neurogenesis [10], apoptosis [19], neuroinflammation [18,24], and oxidative stress [19,20]. Previously, we have found that PTE attenuates neural impairments in different neurological disorders, including glutamate or high-glucose-induced oxidative stress in neural cells [19,20], inflammation and mitochondrial oxidative stress injury after cerebral ischemia reperfusion [18,25], inflammation and oxidation-involved early brain injury following subarachnoid haemorrhage (SAH) [24].…”

Neuroprotective Effects of Qingnao Dripping Pills Against Cerebral Ischemia via Inhibiting NLRP3 Inflammasome Signaling Pathway: In Vivo and In Vitro

“…NF-kB signal pathway is considered to be a vital regulator of inflammation response and is critical to the regulation of apoptosis, plays the important role in ischemic stroke (Harari and Liao, 2010;Li et al, 2019;Liu et al, 2019). NF-kB further promotes the production of NLRP3 and IL-1b and enhancing inflammation (Minutoli et al, 2016;Chen et al, 2019).…”