Ginkgo biloba extract EGb® 761 increases endothelial nitric oxide production in vitro and in vivo

Abstract

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.

Gingko biloba Extract (EGb 761) Prevents Ischemic Brain Injury by Activation of the Akt Signaling Pathway

“…In addition to the antioxidant function of EGb 761, we propose that EGb 761 elicits neuroprotective effect by activation of a survival pathway. A previous study suggests the fact that EGb 761 mediates the Akt signaling pathway (Koltermann et al, 2007). That study confirms that EGb 761 administration significantly decreases the cerebral infarct volume following focal cerebral ischemia by using TTC stain.…”

“…The phosphorylation of Akt, Bad, and FKHR is a critical step for the enhancement of cell survival. EGb 761 treatment acutely enhanced the phosphorylation of Akt (Koltermann et al, 2007). However, there is little information of other downstream targets of Akt such as Bad and FKHR.…”

“…EGb 761 increases the cerebral blood flow and reduces ischemic brain damage (Zhang et al, 2000). Furthermore, EGb 761 protects against endothelial dysfunction through the activation of Akt and subsequent eNOS phosphorylation (Koltermann et al, 2007).…”

Effect of Ginkgo biloba on brain volume after carotid artery occlusion in rats: a stereological and histopathological study

“…One study has suggested that GB acts as a mediator on the Akt signaling pathway (34). Studies have also reported that the volume of cerebral infarct developing after focal cerebral ischemia decreased significantly with administration of GB, and that GB therapy mediated this effect by increasing antiapoptotic signals between the Akt and subsignal pathway (35)(36)(37). Our study results showed that total sham group brain volumes increased compared to the control group, and that this increase was statistically significant.…”

Antiproliferative effect of the Ginkgo biloba extract is associated with the enhancement of cytochrome P450 1B1 expression in estrogen receptor-negative breast cancer cells

“…It was previously reported that the Ginkgo biloba extract exerts an antioxidant effect by scavenging reactive oxygen species (3), reduces platelet aggregation and exhibits neuroprotective properties (4). Previous studies demonstrated the potential benefits of the Ginkgo biloba extract in the treatment of Alzheimer's disease (5), learning and memory deficits (6), cerebrovascular diseases (7), cardiovascular diseases (8), climacteric vasomotor symptoms and postmenopausal syndrome (9,10). It was also demonstrated that the Ginkgo biloba extract possesses antitumor properties (11), may induce cancer cell apoptosis and differentiation and inhibit the progression of human colon cancer (12), hepatocellular carcinoma (13), pancreatic (14) and gastric cancer (15).…”