Rutin Protects Ischemic Stroke-Induced Astrocytic Injury by Activating PRDX1

Ischemic stroke is a highly destructive disease with extremely high mortality and disability rates. So far, there have been few available neuroprotective drugs. Rutin, a natural plant alkaloid derived from the flavonoid class of natural compounds, has been proven to have protective effects against ischemic stroke-induced brain injury via its antioxidant and anti-inflammatory pharmacological effects. However, the mechanisms of rutin's antioxidative and anti-inflammatory effects remain largely unknown. The results showed that rutin alleviated ischemia/reperfusion-induced brain injury, including reduced infarct volume, improved neurological deficits, and decreased glial scar thickness. Rutin also alleviated oxygen-glucose deprivation/reoxygenation (OGD/Re)-induced oxidative stress-related indicators, such as reactive oxygen species, lipid peroxidation levels, 4-hydroxynonenal, and malondialdehyde, as well as pro-inflammatory factors such as interleukin-6, interleukin-1β, and tumor necrosis factor-α in astrocytes, thereby ultimately reducing astrocytic injury and inhibiting the activation of reactive astrocytes. The underlying mechanism is that rutin enhances the enzymatic activity of peroxiredoxin-1 (PRDX1). Knockdown of PRDX1 weakened the pharmacological effects of rutin in inhibiting oxidative stress and inflammatory responses. Finally, rutin could indirectly protect neurons by reducing OGD/Re-induced astrocytic damage and directly reduce OGD/Re-induced damage to primary neurons. Therefore, rutin alleviates ischemic stroke-induced oxidative stress and inflammatory responses in astrocytes, at least partially, by activating PRDX1, thereby inhibiting glial scar formation and exerting neuroprotective effects.