The ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid

Substantial evidence suggests that the accumulation of beta-amyloid (A beta )-derived peptides, and to a lesser extent free radicals, may contribute to the aetiology and/or progression of Alzheimer's disease (AD). Ginkgo bilob a extract (EGb 761) is a well-defined plant extract containing two major gr oups of constituents, i.e. flavonoids and terpenoids. It is viewed as a pol yvalent agent with a possible therapeutic use in the treatment of neurodege nerative diseases of multifactorial origin, e.g. AD. We have investigated h ere the potential effectiveness of EGb 761 against toxicity induced by (A b eta)-derived peptides (A beta(25-35), A beta(1-40) and A beta(1-42)) on hip pocampal primary cultured cells, this area being severely affected in AD. A cc-treatment with EGb 761 concentration-dependently (10-100 mu g/ mt) prot ected hippocampal neurons against toxicity induced by AP fragments, with a maximal and complete protection at the highest concentration tested. Simila r, albeit less potent protective effects were seen with the flavonoid fract ion of the extract (CP 205), while the terpenes were ineffective. Most inte restingly, EGb 761 (100 mu g/mL) was even able to protect (up to 8 h) hippo campal cells from a pre-exposure to A beta(25-35) and A beta(1-40) EGb 761 was also able to both protect and rescue hippocampal cells from toxicity in duced by H2O2, (50-150 mu M), a major peroxide possibly involved in mediati ng AP toxicity. Moreover, EGb 761 (10-100 mu g/mL), and to a lesser extent CP 205 (10-50 mu g/mL), completely blocked A beta-induced events, e,g, reac tive oxygen species accumulation and apoptosis. These results suggest that the neuroprotective effects of EGb 761 are partly associated with its antio xidant properties and highlight its possible effectiveness in neurodegenera tive diseases, e.g. AD via the inhibition of A beta-induced toxicity and ce ll death.