Induction of heme oxygenase-1 by Ginkgo Biloba Extract but not its terpenoids partially mediated its protective effect against lysophosphatidylcholine-induced damage

In this study, we examined whether Ginkgo Biloba Extract and its terpenoid constituents protect against oxidative stress through actions on heme oxygenase (HO) gene expression and activity. HO-1 and glutathione peroxidase (GPx) gene expressions were examined by reverse transcription polymerase chain reaction (RT-PCR) analysis, HO activity and GPx enzyme activity were analysed by spectrophotometric assay. Pretreatment of H9c2 myocytes with 100-500 mug ml(-1) Ginkgo Biloba Extract caused induction of HO-1 gene expression and a significant increase in HO activity; 30 mug ml(-1) ginkgolide B and 30 mug ml(-1) bilobalide had little effect. Treatment with Ginkgo Biloba Extract for 24 h also significantly increased GPx gene expression and GPx enzyme activity. Pretreatment with Ginkgo Biloba Extract, ginkgolide B and bilobalide protected myocytes against lysophosphatidylcholine (LPC)-induced damage. The protective effect of Ginkgo Biloba Extract against LPC-induced damage was partially suppressed by a HO inhibitor, Zinc protoporphyrin-IX (ZnPP-IX), while ZnPP-IX did not suppress the protective effect of ginkgolide B or bilobalide. Furthermore, pretreatment with hemin, biliverdin or bilirubin reduced cytotoxicity induced by LPC. These results suggest that induction of HO-1 by Ginkgo Biloba Extract but not its terpenoid constituents may play a beneficial role in oxidative stress. The mechanism of Ginkgo Biloba Extract-induced HO-1 gene expression and the increase in HO activity may be related to alteration of intracellular glutathione levels. (C) 2001 Academic Press.