TY - JOUR T1 - Silibinin Attenuates Amyloid β<sub>25–35</sub> Peptide-Induced Memory Impairments: Implication of Inducible Nitric-Oxide Synthase and Tumor Necrosis Factor-α in Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 319 LP - 326 DO - 10.1124/jpet.109.155069 VL - 331 IS - 1 AU - P. Lu AU - T. Mamiya AU - L. L. Lu AU - A. Mouri AU - M. Niwa AU - M. Hiramatsu AU - L. B. Zou AU - T. Nagai AU - T. Ikejima AU - T. Nabeshima Y1 - 2009/10/01 UR - http://jpet.aspetjournals.org/content/331/1/319.abstract N2 - In Alzheimer’s disease (AD), the deposition of amyloid peptides is invariably associated with oxidative stress and inflammatory responses. Silibinin (silybin), a flavonoid derived from the herb milk thistle, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether silibinin improves amyloid β (Aβ) peptide-induced neurotoxicity. In this study, we examined the effect of silibinin on the fear-conditioning memory deficits, inflammatory response, and oxidative stress induced by the intracerebroventricular injection of Aβ peptide25–35 (Aβ25–35) in mice. Mice were treated with silibinin (2, 20, and 200 mg/kg p.o., once a day for 8 days) from the day of the Aβ25–35 injection (day 0). Memory function was evaluated in cued and contextual fear-conditioning tests (day 6). Nitrotyrosine levels in the hippocampus and amygdala were examined (day 8). The mRNA expression of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) in the hippocampus and amygdala was measured 2 h after the Aβ25–35 injection. We found that silibinin significantly attenuated memory deficits caused by Aβ25–35 in the cued and contextual fear-conditioning test. Silibinin significantly inhibited the increase in nitrotyrosine levels in the hippocampus and amygdala induced by Aβ25–35. Nitrotyrosine levels in these regions were negatively correlated with memory performance. Moreover, real-time RT-PCR revealed that silibinin inhibited the overexpression of iNOS and TNF-α mRNA in the hippocampus and amygdala induced by Aβ25–35. These findings suggest that silibinin (i) attenuates memory impairment through amelioration of oxidative stress and inflammatory response induced by Aβ25–35 and (ii) may be a potential candidate for an AD medication. © 2009 by The American Society for Pharmacology and Experimental Therapeutics ER -