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.


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.
Chen
Jaw-Wen
JW
National Yang-Ming University School of Medicine, Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan, Republic of China. jwchen@vghtpe.gov.tw
Chen
Yung-Hsiang
YH
Lin
Feng-Yan
FY
Chen
Yuh-Lien
YL
Lin
Shing-Jong
SJ
D001011:Aorta / Q000166:cytology; D001161:Arteriosclerosis / Q000517:prevention & control; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D016328:NF-kappa B / Q000502:physiology; D010452:Peptide Biosynthesis / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha