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

Abstract

Background and purpose: Accumulated evidence suggests that oxidative stress is involved in amyloid beta (Abeta)-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 Abeta-induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by Abeta(25-35) in mice.

Experimental approach: Aggregated Abeta(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 Abeta(25-35). Locomotor activity was evaluated 6 days after the Abeta(25-35) treatment, and cognitive function was evaluated in a Y-maze and novel object recognition tests 6-11 days after the Abeta(25-35) treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the Abeta(25-35) injection.

Key results: Silibinin prevented the memory impairment induced by Abeta(25-35) in the Y-maze and novel object recognition tests. Repeated treatment with silibinin attenuated the Abeta(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 Abeta(25-35) and may be a potential therapeutic agent for Alzheimer's disease.

Figure 1

(A) Chemical structure of silibinin and (B) protocol used in this study.

Figure 2

Effects of silibinin on locomotor activity (A) and impairment of short-term memory in Y-maze test (B) in amyloid β (Aβ)_25–35-injected mice. Results are expressed as the means ± s.e.mean (A: n= 8, B: n= 13–15) and were analysed by a one or two-way anova, followed by Tukey's test for multiple comparisons. #P < 0.05 versus carboxymethylcellulose (CMC)-treated, distilled water-injected mice; *P < 0.05 versus CMC-treated, Aβ_25–35-injected mice.

Figure 3

Effect of silibinin on recognition memory impairments induced by amyloid β (Aβ)_25–35 in the novel object recognition test. (A) Preference index in training session. (B) Total exploration time in training session. (C) Recognition index in retention session. (D) Total exploration time in retention session. Results are expressed as the means ± s.e.mean (n= 13–15) and analysed by a one-way anova, followed by Tukey's test for multiple comparisons. #P < 0.05 versus carboxymethylcellulose (CMC)-treated, distilled water-injected mice; *P<0.05 versus CMC-treated, Aβ_25–35-injected mice.

Figure 4

Effects of silibinin on amyloid β (Aβ)_25–35-induced increase in malondialdehyde (MDA) levels and decrease in glutathione (GSH) levels in the hippocampus. (A) MDA levels. (B) GSH levels. Results are expressed as the means ± s.e.mean (n= 6–7) and analysed by a one-way anova, followed by Tukey's test for multiple comparisons. #P < 0.05 versus carboxymethylcellulose (CMC)-treated, distilled water-injected mice; *P < 0.05 versus CMC-treated, Aβ_25–35-injected mice.