Ginkgo biloba extract EGb 761 increases endothelial nitric oxide production in vitro and in vivo.
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.
Koltermann
A
A
Department of Pharmacy, Pharmaceutical Biology, University of Munich, Butenandtstr. 5 -13, 81377, Munich, Germany.
Hartkorn
A
A
Koch
E
E
Fürst
R
R
Vollmar
A M
AM
Zahler
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D020441:Ginkgo biloba; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014664:Vasodilation / Q000187:drug effects; D000096983:Ginkgo Extract
D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D010768:Phosphoserine; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C496314:NOS3 protein, human