Silibinin prevents amyloid β peptide-induced memory impairment and oxidative stress in mice

Background and purpose: Accumulated evidence suggests that oxidative stress is involved in amyloid beta (A beta)-induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silibinin improves A beta-induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by A beta(25-35) in mice. Experimental approach: Aggregated A beta(25-35) (3 nmol) was intracerebroventricularly administered to mice. Treatment with silibinin (2, 20 and 200 mg center dot kg(-1), once a day, p.o.) was started immediately after the injection of A beta(25-35). Locomotor activity was evaluated 6 days after the A beta(25-35) treatment, and cognitive function was evaluated in a Y-maze and novel object recognition tests 6-11 days after the A beta(25-35) treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the A beta(25-35) injection. Key results: Silibinin prevented the memory impairment induced by A beta(25-35) in the Y-maze and novel object recognition tests. Repeated treatment with silibinin attenuated the A beta(25-35)-induced accumulation of malondialdehyde and depletion of glutathione in the hippocampus. Conclusions and implications: Silibinin prevents memory impairment and oxidative damage induced by A beta(25-35) and may be a potential therapeutic agent for Alzheimer's disease.