Abstract: Abstract: Objective To investigate the effect of total flavones of bidens bipinnata L. (TFB) on cognitive function in rats with focal cerebral ischemia and its possible mechanism. Methods Seventy-two rats were randomly divided into sham operation group, model group, positive control group (1 mg/kg nimodipine), low-dose TFB group (25 mg/kg), medium-dose TFB group (50 mg/kg) and high-dose TFB group (100 mg/kg). The rat model of focal cerebral ischemia was established by modified thread embolization. Morris water maze test was used to test the learning and memory abilities of rats. The histopathological changes of hippocampus were observed by Nissl staining. The contents of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in hippocampus were detected by enzyme-linked immunosorbent assay. Western blot assay was used to detect the expressions of ERK1/2, p-ERK1/2, NF-κB p65 and p-NF-κB p65 in hippocampus. Results Compared with the sham-operated group, the average escape latency increased, the number of crossing plateau decreased, the contents of BDNF and NGF in hippocampus decreased and the contents of IL-1β, IL-6 and TNF-α, and the expressions of p-ERK1/2 and p-NF-κB p65 protein increased in the model group (P＜0.05). Compared with model group, the average escape latency of rats decreased after the second day in high dose TFB group and positive control group (P＜0.05). The number of times of rats crossing the platform increased in middle and high dose TFB groups and positive control group, and the contents of BDNF and NGF in hippocampus were also increased (P＜0.05). The contents of IL-1β, IL-6 and TNF-α and the expression levels of p-ERK1/ 2 and p-NF-kappa B p65 were all decreased in a dose-dependent manner (P＜0.05). There were no significant differences in detection indexes between positive control group and high-dose TFB group (P＞0.05). Conclusion TFB can improve cognitive function in rats with focal cerebral ischemia, and its mechanism may be related to the inhibition of ERK1/2/NF-κB signaling pathway.

Key words: brain ischemia, cognition, nerve growth factors, brain-derived neurotrophic factor, extracellular signalregulated MAP kinases, NF-kappa B, total flavones of bidens bipinnata L.