Protective Effect of Bajijiasu Against β-Amyloid-Induced Neurotoxicity in PC12 Cells

Beta-amyloid peptide (A beta), a major protein component of senile plaques associated with Alzheimer's disease (AD), is also directly neurotoxic. Mitigation of A beta-induced neurotoxicity is thus a possible therapeutic approach to delay or prevent onset and progression of AD. This study evaluated the protective effect of Bajijiasu (beta- d-fructofuranosyl (2-2) beta- d-fructofuranosyl), a dimeric fructose isolated from the Chinese herb Radix Morinda officinalis, on A beta-induced neurotoxicity in pheochromocytoma (PC12) cells. Bajijiasu alone had no endogenous neurotoxicity up to 200 mu M. Brief pretreatment with 10-40 mu M Bajijiasu (2 h) significantly reversed the reduction in cell viability induced by subsequent 24 h exposure to A beta(25-35) (21 mu M) as measured by MTT and LDH assays, and reduced A beta(25-35)-induced apoptosis as indicated by reduced annexin V-EGFP staining. Bajijiasu also decreased the accumulation of intracellular reactive oxygen species and the lipid peroxidation product malondialdehyde in PC12 cells, upregulated expression of glutathione reductase and superoxide dismutase, prevented depolarization of the mitochondrial membrane potential (Im), and blocked A beta(25-35)-induced increases in [Ca2+] (i) . Furthermore, Bajijiasu reversed A beta(25-35)-induced changes in the expression levels of p21, CDK4, E2F1, Bax, NF-kappa B p65, and caspase-3. Bajijiasu is neuroprotective against A beta(25-35)-induced neurotoxicity in PC12 cells, likely by protecting against oxidative stress and ensuing apoptosis.