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The present study was carried out to investigate the neuroprotective effect of luteolin on amyloid β (Aβ) (25-35)-induced neurotoxicity using cultured rat cortical neurons. After exposure of primary cultures of rat cortical cells to 10 μ M Aβ (25-35) for 48 h, cortical cell cultures exhibited marked apoptotic death. Pretreatment with luteolin (1, 10 μ M) significantly protected cortical cell cultures against Aβ (25-35)-induced toxicity. Luteolin (1, 10 μ M) showed a concentration-dependent inhibition on 10 μ M Aβ (25-35)-induced apoptotic neuronal death, as assessed by MTT assay. Furthermore, luteolin reduced apoptotic characteristics by DAPI staining. For Western blot analysis, the results showed that the protective effect of luteolin on Aβ (25-35)-induced neurotoxicity was mediated by preventing of ERK-p, JNK, JNK-p, P38-p and caspase 3 activations in rat primary cortical cultures. Taken together, the results suggest that luteolin prevents Aβ (25-35)-induced apoptotic neuronal death through inhibiting the protein level of JNK, ERK and p38 MAP kinases and caspase 3 activations. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]