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The Ginkgo biloba Extract (EGb 761) Protects and Rescues Hippocampal Cells Against Nitric Oxide‐Induced Toxicity
Author(s) -
Bastianetto Stéphane,
Zheng WenHua,
Quirion Rémi
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0742268.x
Subject(s) - chelerythrine , ginkgo biloba , pharmacology , sodium nitroprusside , chemistry , nitric oxide , neuroprotection , protein kinase c , nitric oxide synthase , biochemistry , kinase , biology , organic chemistry
An excess of the free radical nitric oxide (NO) is viewed as a deleterious factor involved in various CNS disorders. Numerous studies have shown that the Ginkgo biloba extract EGb 761 is a NO scavenger with neuroprotective properties. However, the mechanisms underlying its neuroprotective ability remain to be fully established. Thus, we investigated the effect of different constituents of EGb 761, i.e., flavonoids and terpenoids, against toxicity induced by NO generators on cells of the hippocampus, a brain area particularly susceptible to neurodegenerative damage. Exposure of rat primary mixed hippocampal cell cultures to either sodium nitroprusside (SNP; 100 μ M ) or 3‐morpholinosydnonimine resulted in both a decrease in cell survival and an increase in free radical accumulation. These SNP‐induced events were blocked by either EGb 761 (10‐100 μg/ml) or its flavonoid fraction CP 205 (25 μg/ml), as well as by inhibitors of protein kinase C (PKC; chelerythrine) and L‐type calcium channels (nitrendipine). In contrast, the terpenoid constituents of EGb 761, known as bilobalide and ginkgolide B, as well as inhibitors of phospholipases A [3‐[(4‐octadecyl)benzoyl]acrylic acid (OBAA)] and C (U‐73122), failed to display any significant effects. Moreover, EGb 761 (50 μg/ml), CP 205 (25 μg/ml), and chelerythrine were also able to rescue hippocampal cells preexposed to SNP (up to 1 m M ). Finally, EGb 761 (100 μg/ml) was shown to block the activation of PKC induced by SNP (100 μ M ). These data suggest that the protective and rescuing abilities of EGb 761 are not only attributable to the antioxidant properties of its flavonoid constituents but also via their ability to inhibit NO‐stimulated PKC activity.