Biol. Pharm. Bull. 28(2) 289—293 (2005)

neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and some ischemia-induced dementia. Ideal treatment and prevention for these diseases would interrupt the degenerative procedure specific to each disease, such as the trial of a b-secretase inhibitor to reduce the production of toxic amyloid b peptides that play key roles in Alzheimer’s disease. However, there is still a long way to go to clarify their deleterious mechanisms, which may be initiated by toxic insults, viral infection, imbalance of nutrients, genetic defaults, natural aging 7) or complex interactions among them. Therefore offering protective agents to rescue damaged neurons from death is regarded as a practicable strategy for the control of neurodegenerative diseases. Several compounds acting with different protective mechanisms are currently in development and a few are in clinical trials, including antioxidants, vitamins, endogenous neurotrophins, and neurotrophin functional mimetics. Our ongoing project to search for small-molecular functional mimetics of neurotrophins from natural products resulted in the discovery of a promising 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignan, talaumidin (1), which was isolated from Aristolochia arcuata MASTERS and was confirmed to promote neurite outgrowth and neuronal survival in cultured rat cortical neurons. Our continued work led to the isolation of six previously known neolignans (2—7) (Fig. 1) from a methanol extract of the same plant. In this paper, we report the neurotrophic effects of these 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignans (2—7) for comparison with 1, the neuroprotective effects of neolignans (1—7) against Ab25—35-induced cell death in primary cultured rat hippocampal neurons, as well as against cell death induced by 1methyl-4-phenylpyridinium ion (MPP ), a neurotoxin used in the cellular model for Parkinson’s disease. MATERIALS AND METHODS