Ginkgo biloba extract EGb® 761 increases endothelial nitric oxide production in vitro and in vivo
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- Koltermann, A., Hartkorn, A., Koch, E. et al. Cell. Mol. Life Sci. (2007) 64: 1715. doi:10.1007/s00018-007-7085-z
Beneficial effects of Ginkgo biloba on peripheral arterial occlusive disease have been repeatedly shown in clinical trials, especially after use of EGb® 761, a standardized special extract. Since the underlying mechanisms are widely unknown, we aimed to elucidate the molecular basis on which EGb® 761 protects against endothelial dysfunction in vitro and in vivo. Application of therapeutically feasible doses of EGb® 761 for 48 h caused endothelial nitric oxide (NO) production by increasing endothelial nitric oxide synthase (eNOS) promoter activity and eNOS expression in vitro. Phosphorylation of eNOS at a site typical for Akt (Ser 1177) was acutely enhanced by treatment with EGb® 761, as was Akt phosphorylation at Ser 478. Furthermore, the extract caused acute relaxation of isolated aortic rings and NO-dependent reduction of blood pressure in vivo in rats. These influences on eNOS represent a putative molecular basis for the protective cardiovascular properties of EGb® 761.