Ginkgo biloba extract reduces high-glucose-induced endothelial reactive oxygen species generation and cell adhesion molecule expression by enhancing HO-1 expression via Akt/eNOS and p38 MAP kinase pathways.

Abstract

AIM:

Hyperglycemia is one of the major risk factors leading to vascular complications in clinical diabetes mellitus. Ginkgo biloba extract (GBE), an antioxidant herbal medicine, possesses anti-inflammatory effects. We examined whether GBE can reduce high glucose-induced endothelial adhesiveness to monocytes, an in vitro sign mimicking in vivo early atherogenesis, through selective regulation of heme oxygenase (HO)-1 expression.

METHODS:

Human aortic endothelial cells (HAECs) were cultured with normal glucose or high glucose (25 mM) for 4 days and subsequently combined with GBE (EGb761, Dr. Willmar Schwabe, Karlsruhe, Germany) treatment in the last 18 h of the 4-day period. The endothelial reactive oxygen species (ROS) generation, adhesion molecule expression and the adhesiveness to monocytes were examined. The specific signal pathways such as HO-1 were also examined.

RESULTS:

High glucose increased ROS generation, adhesion molecule expression and the adhesiveness to monocytes in HAECs. These high glucose-induced phenomena could be suppressed by GBE (100 μg/ml)-induced HO-1 expression in a dose-dependent and time-dependent manner. In addition, jun N-terminal kinases inhibitor or phosphoinositide 3 kinase inhibitor could reduce GBE-induced HO-1 expression. Furthermore, HO-1 inhibitor, HO-1 siRNA, endothelial nitric oxide synthase (eNOS) siRNA, or nuclear factor erythroid 2-related factor (Nrf) 2 siRNA blocked the cytoprotective effects of GBE. Meanwhile, p38/mitogen-activated protein kinase (MAPK) inhibitor could also reduce the effects of GBE on HO-1 induction.

CONCLUSION:

GBE could reduce high glucose-induced endothelial adhesion via enhancing HO-1 expression through the Akt/eNOS and p38/MAPK pathways. Our findings suggest a potential strategy targeting on HO-1 induction by GBE for endothelial protection in the presence of high glucose such as that in diabetes mellitus.

• Authors: Hsiao-Ya Tsai, Po-Hsun Huang, Feng-Yen Lin, Jia-Shiong Chen, Shing-Jong Lin, Jaw-Wen Chen
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 48 Issue 4-5 Pg. 803-11 (Mar 12 2013) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 23357604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Plant Extracts
• Reactive Oxygen Species
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Nitric Oxide
• NOS3 protein, human
• Nitric Oxide Synthase Type III
• HMOX1 protein, human
• Heme Oxygenase-1
• Mitogen-Activated Protein Kinases
• Glucose

Topics

• Cell Adhesion (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Endothelial Cells (drug effects, physiology)
• Gene Knockdown Techniques
• Ginkgo biloba
• Glucose
• Heme Oxygenase-1 (genetics, metabolism)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Monocytes (drug effects, physiology)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (genetics, metabolism)
• Plant Extracts (pharmacology)
• Reactive Oxygen Species (metabolism)
• Vascular Cell Adhesion Molecule-1 (metabolism)