Effects of icariin combined with Panax notoginseng saponins on ischemia reperfusion-induced cognitive impairments related with oxidative stress and CA1 of hippocampal neurons in rat

Previous studies suggest that treatment with icariin (ICA) combined with Panax notoginseng saponins (PNS) improved behavior and cholinergic system disorders followed by amyloid beta-peptide(25-35) lateral ventricle injection in rats. The present study investigated whether administration of ICA + PNS had preventive and therapeutic effects on bilateral common carotid arteries (CCA) occlusion-induced cerebral ischemia-reperfusion (IR) injury in rats. Male Sprague-Dawley rats were divided randomly as follows: sham-operated, i.g. vehicle, ICA (5 mg/kg), PNS (40 mg/kg), ICA + PNS (2.5 + 20, 5 + 40 or 10 + 80 mg/kg), and ergoloid mesylate as a positive control (0.45 mg/kg) in model rats. Treatment was performed once a day for 7 days prior to ischemia. The rats were subjected to transient global IR induced by CCA occlusion in combination with intraperitoneal injection of sodium nitroprusside (2.0 mgtkg), then treated with ICA + PNS for another 14 days continuously. ICA + PNS significantly improved the rat passive avoidance task in step-down paradigms, and spatial cognition in the eight-arm radial maze, concomitant with an improvement of blood viscosity. Increased lipid peroxidation in brain after IR injury was observed, MDA being 0.56 +/- 0.10 nmol/mg prot vs 0.48 +/- 0.06 nmol/mg prot in the vehicle control (p < 0.05). Treatment with ICA + PNS 2.5 + 109 5 + 40, 10 + 80 mg/kg produced a marked reduction in the MDA level to 0.46 +/- 0.06, 0.42 +/- 0.09 and 0.45 +/- 0.08 nmol/mg prot, respectively vs 0.56 0.10 nmol/mg prot in IR injury only control (p < 0.05, p < 0.01). A decrease in superoxide dismutase activity was observed in the brain of IR rats (the SOD activity being 72.75 +/- 4.62 U/mg prot vs 80.97 +/- 6.06 U/mg prot in control, p < 0.05). ICA + PNS 5 + 40 mg/kg prevented the IR injury mediated fall in superoxide dismutase activity being 78.90 +/- 6.61 U/mg prot versus 72.75 4.62 U/mg prot (p < 0.05). ICA + PNS tended to attenuate apoptosis in hippocampal CA1 pyramidal neurons. Either ICA or PNS treatment alone did not obviously improve cognitive impairment (except that lipid peroxidation was reduced by PNS-treatment). The results indicated that ICA + PNS may ameliorate learning and memory deficit and blood viscosity by protecting neurons from oxidative stress in ischemic brain. Copyright (C) 2008 John Wiley & Sons, Ltd.