Ginkgo biloba extract inhibits tumor necrosis factor-alpha-induced reactive oxygen species generation, transcription factor activation, and cell adhesion molecule expression in human aortic endothelial cells.

OBJECTIVE: This study was conducted to examination whether Ginkgo biloba extract (GBE), a Chinese herb with antioxidant activity, could reduce cytokine-induced monocyte/human aortic endothelial cell (HAEC) interaction, a pivotal early event in atherogenesis.

METHODS AND RESULTS: Pretreatment of HAECs with GBE (50 and 100 microg/mL for 18 hours) significantly suppressed cellular binding between the human monocytic cell line U937 and tumor necrosis factor-alpha (TNF-alpha)-stimulated HAECs by using in vitro binding assay (68.7% and 60.1% inhibitions, respectively). Cell enzyme-linked immunosorbent assay and immunoblot analysis showed that GBE (50 microg/mL for 18 hours) significantly attenuated TNF-alpha-induced cell surface and total protein expression of vascular cellular adhesion molecule-1 and intracellular adhesion molecule-1 (63.5% and 69.2%, respectively; P<0.05). However, pretreatment with probucol (5 micromol/L for 18 hours) reduced the expression of vascular cellular adhesion molecule-1 but not intracellular adhesion molecule-1. Preincubation of HAECs with GBE or probucol significantly reduced intracellular reactive oxygen species formation induced by TNF-alpha (76.8% and 68.2% inhibitions, respectively; P<0.05). Electrophoretic mobility shift assay demonstrated that both GBE and probucol inhibited transcription factor nuclear factor-kappaB activation in TNF-alpha-stimulated HAECs (55.2% and 65.6% inhibitions, respectively) but only GBE could inhibit the TNF-alpha-stimulated activator protein 1 activation (45.1% inhibition, P<0.05).

CONCLUSIONS: GBE could reduce cytokine-stimulated endothelial adhesiveness by downregulating intracellular reactive oxygen species formation, nuclear factor-kappaB and activator protein 1 activation, and adhesion molecule expression in HAECs, supporting the notion that the natural compound Ginkgo biloba may have potential implications in clinical atherosclerosis disease.