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

Hsiao Ya Tsai, Po Hsun Huang, Feng Yen Lin, Jia Shiong Chen, Shing Jong Lin, Jaw Wen Chen

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)803-811
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Volume48
Issue number4-5
DOIs
Publication statusPublished - Mar 12 2013

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Ginkgo biloba
Heme Oxygenase-1
MAP Kinase Signaling System
Nitric Oxide Synthase Type III
Cell Adhesion Molecules
p38 Mitogen-Activated Protein Kinases
Reactive Oxygen Species
Glucose
Adhesiveness
Small Interfering RNA
Monocytes
Diabetes Mellitus
Endothelial Cells
1-Phosphatidylinositol 4-Kinase
Herbal Medicine
Protein Kinase Inhibitors
Hyperglycemia
Germany
Blood Vessels
Signal Transduction

Keywords

  • Adhesion molecule
  • Endothelial nitric oxide synthase
  • Ginkgo biloba extract
  • Heme oxygenase-1
  • High glucose
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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. / Tsai, Hsiao Ya; Huang, Po Hsun; Lin, Feng Yen; Chen, Jia Shiong; Lin, Shing Jong; Chen, Jaw Wen.

In: European Journal of Pharmaceutical Sciences, Vol. 48, No. 4-5, 12.03.2013, p. 803-811.

Research output: Contribution to journalArticle

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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.",
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T1 - 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

AU - Tsai, Hsiao Ya

AU - Huang, Po Hsun

AU - Lin, Feng Yen

AU - Chen, Jia Shiong

AU - Lin, Shing Jong

AU - Chen, Jaw Wen

PY - 2013/3/12

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N2 - 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.

AB - 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.

KW - Adhesion molecule

KW - Endothelial nitric oxide synthase

KW - Ginkgo biloba extract

KW - Heme oxygenase-1

KW - High glucose

KW - Reactive oxygen species

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