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

Abstract

Background and purpose: Accumulated evidence suggests that oxidative stress is involved in amyloid β (Aβ)‐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 Aβ‐induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by Aβ 25–35 in mice. Experimental approach: Aggregated Aβ 25–35 (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 Aβ 25–35. Locomotor activity was evaluated 6 days after the Aβ 25–35 treatment, and cognitive function was evaluated in a Y‐maze and novel object recognition tests 6–11 days after the Aβ 25–35 treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the Aβ 25–35 injection. Key results: Silibinin prevented the memory impairment induced by Aβ 25–35 in the Y‐maze and novel object recognition tests. Repeated treatment with silibinin attenuated the Aβ 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 Aβ 25–35 and may be a potential therapeutic agent for Alzheimer's disease.