Effects of echinacoside on GDNF expression and mitochondrial oxidative stress levels in vascular dementia rats

Mitochondrial oxidation injury plays a critical role in pathogenesis of vascular dementia (VD) in rats. Glial cell line-derived neurotrophic factor (GDNF) is related with cognitive functions. Echinacoside (ECH) protects learning and memory functions of VD rats. This study thus investigated the effect of ECH on GDNF expression and mitochondrial oxidative stress level in VD rat brain at genetic and molecular levels. Healthy male SD rats (4 months old) were randomly assigned into sham, model and ECH groups (30 mg/kg). VD model was generated by the ligation of bilateral common carotid artery. ECH group received drug treatment for 4 consecutive weeks. Morris water-maze was used to test memory function of rats, while HE staining was used to observe morphology of brain tissues. Superoxide dismutase (SOD), reactive oxygen species (ROS) in mitochondrial were quantified from hippocampus. Western blot was used to test the expression of silent information regulator 3 (Sirt3), while hippocampal GDNF level was assayed by immunohistochemistry (IHC) staining. VD model rats had elongated escape latency and lower platform crossing times, plus significant injury of hippocampal CA1 regions. Model rats had elevated ROS contents, and suppressed SOD activity, Sirt3 or GDNF expression (P<0.05). ECH treated rats had shorter escape latency and more platform crossing times, significantly improved hippocampal injury, lower ROS contents, and elevated SOD activity, Sirt3 and GDNF expression (P<0.05). ECH can alleviate ischemia injury of VD rat neurons and improve learning and memory functions, via modulating oxidative response level of mitochondria, and upregulating hippocampal GDNF expression.