Background and purpose: Accumulated evidence suggests that oxidative stress is involved in amyloid b (Ab)-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 Ab-induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by Ab25-35 in mice. Experimental approach: Aggregated Ab25-35 (3 nmol) was intracerebroventricularly administered to mice. Treatment with silibinin (2, 20 and 200 mg-kg-1, once a day, p.o.) was started immediately after the injection of Ab25-35. Locomotor activity was evaluated 6 days after the Ab25-35 treatment, and cognitive function was evaluated in a Y-maze and novel object recognition tests 6-11 days after the Ab25-35 treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the Ab25-35 injection. Key results: Silibinin prevented the memory impairment induced by Ab25-35 in the Y-maze and novel object recognition tests. Repeated treatment with silibinin attenuated the Ab25-35-induced accumulation of malondialdehyde and depletion of glutathione in the hippocampus. Conclusions and implications: Silibinin prevents memory impairment and oxidative damage induced by Ab25-35 and may be a potential therapeutic agent for Alzheimer's disease.
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