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


METHODS
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.


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
Silibinin prevents memory impairment and oxidative damage induced by Abeta(25-35) and may be a potential therapeutic agent for Alzheimer's disease.
Lu
P
P
Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Japan.
Mamiya
T
T
Lu
L L
LL
Mouri
A
A
Zou
Lb
L
Nagai
T
T
Hiramatsu
M
M
Ikejima
T
T
Nabeshima
T
T
D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000502:physiology* / Q000633:toxicity; D000818:Animals; D005106:Exploratory Behavior / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000502:physiology* / Q000633:toxicity; D021641:Recognition, Psychology / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012838:Silymarin; C074636:amyloid beta-protein (25-35); D000077385:Silybin; D008315:Malondialdehyde; D005978:Glutathione