Allixin, a phytoalexin produced by garlic, and its analogues as novel exogenous substances with neurotrophic activity

Abstract Effects of allixin, a phytoalexin of garlic, and its analogues were studied on the survival and morphology of primary cultured neurons from fetal rat brain. Addition of allixin (1–100 ng ml ) to medium significantly promoted the survival of neurons derived from various regions of brain and increased the number of branching points per axon in hippocampal neurons. Allixin, however, was cytotoxic at higher concentrations (> 1 μg ml ). Among the analogues of allixin, 2,6-dimethyl-3-hydroxy-4 H -pyran-4-one (DHP) possessed potent neurotrophic activity at concentrations over 10 ng ml without any obvious cytotoxicity up to 10 μg ml . DHP also retained the activity to promote axonal branching. These results indicate that DHP is a novel exogenous low molecular weight neurotrophic substance without apparent cytotoxicity. This compound may be a useful prototype leading chemical for developing therapeutic and/or prophylactic drugs for neurodegenerative disorders.