Silibinin attenuates learning and memory deficits through inflammation mechanism in intracerebroventricular-A1-42 injected mice

Objective To investigate the effects and mechanism of silibinin on learning and memory in mice with Alzheimer's disease.Methods Alzheimer's disease model was established by intracerebroventricular injection of amyloid protein β(Aβ_1-42)in 50 mice and then the mice were randomly divided into a control group, a model group, 2 silibinin groups(100 and 200 mg/kg), and a positive control group(1.3 mg/kg of donepezil).Learning and memory of the mice was evaluated with Y maze test.Western blot and enzyme-linked immunosorbent assay(ELISA)were adopted to detect the expressions of tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1β), interleukin-6(IL-6), and interleukin-4(IL-4).Results Compared with those of the control group, the preference index of novel object recognition test at one hour(0.53±0.09)and 24 hour(0.51±0.12)and spontaneous alternation response rate of Y maze test(0.52±0.09%)decreased significantly for the mice in the model group(P<0.01).Compared with those of the model group, the preference index of novel object recognition test at one hour(0.67±0.11)and 24 hour(0.69±0.11)and spontaneous alternation response rate of Y maze test(0.72%±0.09%, P<0.01)increased significantly for the mice in 200 mg/kg silibinin treatment group.Compared with those of the control group, the level of IL-4 decreased, but TNF-α and IL-1β increased significantly in hippocampus of the mice of the model group(all P<0.01).Compared with those of the model group, the level of IL-4 increased, but TNF-α and IL-1β decreased in hippocampus of the mice of 200 mg/kg silibinin treatment group.Conclusion Silibinin could improve learning and memory disorder of the mice with intracerebroventricular-Aβ_1-42 injection and the effects may be related to the regulation of inflammation factors in the brain.