Protective role of wogonin following traumaticbrain injury by reducing oxidative stress and apoptosis via the PI3K/Nrf2/HO‑1 pathway.

Abstract

Traumatic brain injury (TBI) is usually caused by accidental injuries and traffic accidents, with a very high mortality rate. Treatment and management following TBI are essential to reduce patient injury and help improve long-term prognosis. Wogonin is a flavonoid compound with an antioxidant effect extracted from Scutellaria baicalensis Georgi. However, the function and mechanism of wogonin in protecting brain injury remain to be elucidated. The present study established a TBI model of Sprague-Dawley rats and treated them with wogonin following trauma. The results showed that wogonin treatment significantly reduced neurobehavioral disorders, brain edema and hippocampal neuron damage caused by TBI. It was found that in TBI rats, administration of wogonin increased the levels of antioxidant factors glutathione, superoxide dismutase and catalase in the CA1 region of the hippocampus and significantly inhibited the production of malondialdehyde and reactive oxygen species. western blotting data showed that wogonin exerted antioxidant activity by downregulating the level of NOX2 protein. In inhibiting cell apoptosis, wogonin upregulated the expression of Bcl-2 protein in the hippocampal CA1 region of TBI rats and inhibited caspase-3 and Bax proteins. Additionally, wogonin inhibited the progression of injury following TBI through the PI3K/Akt/nuclear factor-erythroid factor 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Wogonin increased the expression of phosphorylated Akt, Nrf2 and HO-1 in the hippocampus of TBI rats. Following the administration of PI3K inhibitor LY294002, the upregulation of these proteins by wogonin was partly reversed. In addition, LY294002 partially reversed the regulation of wogonin on NOX2, caspase-3, Bax and Bcl-2 proteins. Therefore, wogonin exerts antioxidant and anti-apoptotic properties to prevent hippocampal damage following TBI, which is accomplished through the PI3K/Akt/Nrf2/HO-1 pathway.