Objectives: Crocin, an active constituent of saffron (Crocus sativus L.) has widely been known for its antioxidant properties, which nominate this herbal compound to be of therapeutic value in the neurodegenerative disorders. Alzheimer’s disease (AD) is a neurodegenerative disorder defined by misfolded protein accumulation and free radicals generation with concurrent neuroinflammation and neuronal death. Herein, it is reported that crocin is capable of protecting neurons against A β1-42 -induced oxidative injury and neuronal death in vitro (P<0.05). Materials & Methods: Primary rat basal forebrain neurons were cultured from 16 to 17 d-old embryos of pregnant Sprague–Dawley rats. Septal regions containing the basal forebrain neurons were dissected in Hank\'s balanced salt solution supplemented with 15 mM HEPES, 10 U/ml penicillin and 10 mg/ml streptomycin, dissociated using 0.05% trypsin, triturated and then plated on poly-D-lysine coated wells. Cultures were grown at 37°C with 5% CO2 in a humidified atmosphere in Neurobasal medium supplemented with N2 Supplement. Results & Conclusion: Experiments were performed 7 d after cell plating for 36 h using the fibrillar aggregated form of the β-Amyloid peptide (Aβ1-42) prepared using a 1 mM solution of Aβ1-42 peptide incubated in PBS at 37°C for 2-3 days. Incubating these neurons with crocin (1-200 µM) could protect them from A β1-42 –induced toxicity in a concentration-dependent manner. These results underscore the potential therapeutic effects of saffron and its active constituent, crocin, in preventing or ameliorating the neuropathogenic outcomes of Alzheimer’s and possibly other neurodegenerative disorders. Keywords: Crocin, saffron, Alzheimer, oxidative injury.

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