Dosage Effects of Ginkgolide B on Ethanol‐Induced Cell Death in Human Hepatoma G2 Cells

Abstract

Ginkgolide B is a major active component of Ginkgo biloba extracts, which has been shown to confer anticancer effects by inducing apoptosis or inhibiting oxidative stress generation. Ethanol induces a wide range of cellular toxicities, many of which have been linked to free radical generation. To further elucidate the cellular effects of ginkgolide B, we examined the dose-response effect of ginkgolide B on ethanol-induced toxicity in human Hep G2 cells. TUNEL and MTT assays revealed that ethanol (50-400 mM) induced apoptotic cell death in human Hep G2 cells, and that this effect was inhibited by low (5-25 microM) doses of ginkgolide B, but enhanced by high (50-100 microM) doses of ginkgolide B. Additional experiments revealed that ethanol treatment directly increased intracellular oxidative stress; this effect was enhanced by high doses of ginkgolide B but decreased following treatment with low concentrations of ginkgolide B. The dose-response effects of ginkgolide B on reactive oxygen species (ROS) generation were directly correlated with cell apoptotic biochemical changes including c-Jun N-terminal kinase (JNK) activation, caspase-3 activation, and DNA fragmentation. These results indicate that treatment dosage may determine the effect of ginkgolide B on ethanol-induced ROS generation and cell apoptosis, and support the notion that an appropriate dosage of ginkgolide B may aid in decreasing the toxic effects of ethanol.