Silibinin Attenuates Amyloid 25–35 Peptide-Induced Memory Impairments: Implication of Inducible Nitric-Oxide Synthase and Tumor Necrosis Factor- in Mice

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 ac-tivities. However, it remains unclear whether silibinin improves amyloid (A) 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 A peptide25–35 (A25–35) 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 A25–35 injection (day 0). Memory function was evaluated in cued and contextual fear-conditioning tests (day 6). Nitroty-rosine levels in the hippocampus and amygdala were examine