RESUMEN
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 longterm 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 SpragueDawley 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 Bcl2 protein in the hippocampal CA1 region of TBI rats and inhibited caspase3 and Bax proteins. Additionally, wogonin inhibited the progression of injury following TBI through the PI3K/Akt/nuclear factorerythroid factor 2related factor 2 (Nrf2)/heme oxygenase1 (HO1) signaling pathway. Wogonin increased the expression of phosphorylated Akt, Nrf2 and HO1 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, caspase3, Bax and Bcl2 proteins. Therefore, wogonin exerts antioxidant and antiapoptotic properties to prevent hippocampal damage following TBI, which is accomplished through the PI3K/Akt/Nrf2/HO1 pathway.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Factor 2 Relacionado con NF-E2 , Animales , Apoptosis , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Flavanonas , Hemo-Oxigenasa 1/metabolismo , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Pre-eclampsia (PE) is a pregnancy-associated disease characterized by placental dysfunction and increased oxidative stress. Apocyanin is a potent antioxidant and anti-inflammatory which has shown beneficial effects on PE pathogenesis. Aspirin is recognized as the recommendable drug in PE prevention and therapy. Therefore, we aimed to investigate the effects of combining apocyanin and aspirin to treat PE on rat models induced by N-nitro-L-arginine methyl ester (L-NAME) from gestational day (GD) 6 to 16 and elucidate the potential mechanisms. METHODS: First, female pregnant rats were divided into five different groups: pregnant control, PE, PE + apocyanin, PE + aspirin, and PE + apocyanin + aspirin. Animals received apocyanin (16 mg/kg/day) orally or aspirin by gavage (1.5 mg/kg BM/day) from GD 4 to 16. Blood pressure and urine protein content were monitored every 4 days. RESULTS: In the PE rat model, elevated systolic blood pressure and proteinuria were ameliorated by the combination of apocyanin and aspirin. Meanwhile, compared with single-dose apocyanin or aspirin, the combined treatment significantly corrected abnormal pregnancy outcomes, decreased sFlt-1 and PlGF, and alleviated oxidative stress both in blood and placental tissues. Moreover, the combined treatment upregulated PI3K, Akt, Nrf2, and HO-1 protein levels in the placental tissues from PE rats. CONCLUSION: Overall, our results suggested that combined treatment of apocyanin and aspirin ameliorates the PE symptoms compared with single-dose apocyanin or aspirin in a PE rat model. Also, we demonstrated that activating the PI3K/Nrf2/HO-1 pathway can be a valuable therapeutic target to improve the pregnancy outcomes of PE.