Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract

Jia Shiong Chen, Po Hsun Huang, Chao Hung Wang, Feng Yen Lin, Hsiao Ya Tsai, Tao Cheng Wu, Shing Jong Lin, Jaw Wen Chen

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Aims: Vascular protective effects of Ginkgo biloba extract (GBE) may involve both antioxidant-related and anti-inflammatory mechanisms. GBE was recently suggested as a heme oxygenase (HO)-1 inducer. The role of HO-1 in anti-atherogenesis and related vascular protective effects of GBE awaited further clarification. Methods and results: Tumor necrosis factor (TNF)-α was used to stimulate adhesiveness of human aortic endothelial cells (HAECs) to monocytes, an in vitro sign simulating atherogenesis. Pretreatment with GBE reduced TNF-α-stimulated endothelial adhesiveness, which could be attenuated by HO-1 inhibitors ZnPP IX or SnPP IX. GBE increased HO-1 expression and enzyme activity in HAECs. Pretreatment with MAP kinase inhibitor SB203580 significantly reduced GBE-induced HO-1 expression. Furthermore, GBE activated the translocation of the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and increased its binding to the antioxidant response element (ARE) of the HO-1 gene. Pretreatment with PEG-SOD or other antioxidant reagents did not alter GBE-induced endothelial HO-1 expression. In vivo study also showed that GBE treatment could reduce leukocyte adherence to injury arteries, and enhance HO-1 expression in circulating monocytes and in arteries after wire injury, suggesting the in vivo induction of HO-1 by GBE. Conclusion: GBE could inhibit cytokine-induced endothelial adhesiveness by inducing HO-1 expression via the activation of p38 and Nrf-2 pathways, a mechanism in which oxidative stress is not directly involved. GBE might exert its anti-atherogenesis and vascular protective effects by inducing vascular HO-1 expression.

Original languageEnglish
Pages (from-to)301-309
Number of pages9
JournalAtherosclerosis
Volume214
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Ginkgo biloba
Heme Oxygenase-1
Blood Vessels
Atherosclerosis
Antioxidants
Adhesiveness
Monocytes
NF-E2 Transcription Factor
Endothelial Cells
Arteries
Tumor Necrosis Factor-alpha
Antioxidant Response Elements
Wounds and Injuries
Human Activities
Oxidative Stress
Leukocytes
Anti-Inflammatory Agents
Phosphotransferases

Keywords

  • Antioxidant
  • Atherogenesis
  • Endothelial cells
  • Ginkgo biloba extract
  • Heme oxygenase-1
  • Nrf-2
  • Wire injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract. / Chen, Jia Shiong; Huang, Po Hsun; Wang, Chao Hung; Lin, Feng Yen; Tsai, Hsiao Ya; Wu, Tao Cheng; Lin, Shing Jong; Chen, Jaw Wen.

In: Atherosclerosis, Vol. 214, No. 2, 02.2011, p. 301-309.

Research output: Contribution to journalArticle

Chen, Jia Shiong ; Huang, Po Hsun ; Wang, Chao Hung ; Lin, Feng Yen ; Tsai, Hsiao Ya ; Wu, Tao Cheng ; Lin, Shing Jong ; Chen, Jaw Wen. / Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract. In: Atherosclerosis. 2011 ; Vol. 214, No. 2. pp. 301-309.
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abstract = "Aims: Vascular protective effects of Ginkgo biloba extract (GBE) may involve both antioxidant-related and anti-inflammatory mechanisms. GBE was recently suggested as a heme oxygenase (HO)-1 inducer. The role of HO-1 in anti-atherogenesis and related vascular protective effects of GBE awaited further clarification. Methods and results: Tumor necrosis factor (TNF)-α was used to stimulate adhesiveness of human aortic endothelial cells (HAECs) to monocytes, an in vitro sign simulating atherogenesis. Pretreatment with GBE reduced TNF-α-stimulated endothelial adhesiveness, which could be attenuated by HO-1 inhibitors ZnPP IX or SnPP IX. GBE increased HO-1 expression and enzyme activity in HAECs. Pretreatment with MAP kinase inhibitor SB203580 significantly reduced GBE-induced HO-1 expression. Furthermore, GBE activated the translocation of the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and increased its binding to the antioxidant response element (ARE) of the HO-1 gene. Pretreatment with PEG-SOD or other antioxidant reagents did not alter GBE-induced endothelial HO-1 expression. In vivo study also showed that GBE treatment could reduce leukocyte adherence to injury arteries, and enhance HO-1 expression in circulating monocytes and in arteries after wire injury, suggesting the in vivo induction of HO-1 by GBE. Conclusion: GBE could inhibit cytokine-induced endothelial adhesiveness by inducing HO-1 expression via the activation of p38 and Nrf-2 pathways, a mechanism in which oxidative stress is not directly involved. GBE might exert its anti-atherogenesis and vascular protective effects by inducing vascular HO-1 expression.",
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T1 - Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract

AU - Chen, Jia Shiong

AU - Huang, Po Hsun

AU - Wang, Chao Hung

AU - Lin, Feng Yen

AU - Tsai, Hsiao Ya

AU - Wu, Tao Cheng

AU - Lin, Shing Jong

AU - Chen, Jaw Wen

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N2 - Aims: Vascular protective effects of Ginkgo biloba extract (GBE) may involve both antioxidant-related and anti-inflammatory mechanisms. GBE was recently suggested as a heme oxygenase (HO)-1 inducer. The role of HO-1 in anti-atherogenesis and related vascular protective effects of GBE awaited further clarification. Methods and results: Tumor necrosis factor (TNF)-α was used to stimulate adhesiveness of human aortic endothelial cells (HAECs) to monocytes, an in vitro sign simulating atherogenesis. Pretreatment with GBE reduced TNF-α-stimulated endothelial adhesiveness, which could be attenuated by HO-1 inhibitors ZnPP IX or SnPP IX. GBE increased HO-1 expression and enzyme activity in HAECs. Pretreatment with MAP kinase inhibitor SB203580 significantly reduced GBE-induced HO-1 expression. Furthermore, GBE activated the translocation of the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and increased its binding to the antioxidant response element (ARE) of the HO-1 gene. Pretreatment with PEG-SOD or other antioxidant reagents did not alter GBE-induced endothelial HO-1 expression. In vivo study also showed that GBE treatment could reduce leukocyte adherence to injury arteries, and enhance HO-1 expression in circulating monocytes and in arteries after wire injury, suggesting the in vivo induction of HO-1 by GBE. Conclusion: GBE could inhibit cytokine-induced endothelial adhesiveness by inducing HO-1 expression via the activation of p38 and Nrf-2 pathways, a mechanism in which oxidative stress is not directly involved. GBE might exert its anti-atherogenesis and vascular protective effects by inducing vascular HO-1 expression.

AB - Aims: Vascular protective effects of Ginkgo biloba extract (GBE) may involve both antioxidant-related and anti-inflammatory mechanisms. GBE was recently suggested as a heme oxygenase (HO)-1 inducer. The role of HO-1 in anti-atherogenesis and related vascular protective effects of GBE awaited further clarification. Methods and results: Tumor necrosis factor (TNF)-α was used to stimulate adhesiveness of human aortic endothelial cells (HAECs) to monocytes, an in vitro sign simulating atherogenesis. Pretreatment with GBE reduced TNF-α-stimulated endothelial adhesiveness, which could be attenuated by HO-1 inhibitors ZnPP IX or SnPP IX. GBE increased HO-1 expression and enzyme activity in HAECs. Pretreatment with MAP kinase inhibitor SB203580 significantly reduced GBE-induced HO-1 expression. Furthermore, GBE activated the translocation of the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and increased its binding to the antioxidant response element (ARE) of the HO-1 gene. Pretreatment with PEG-SOD or other antioxidant reagents did not alter GBE-induced endothelial HO-1 expression. In vivo study also showed that GBE treatment could reduce leukocyte adherence to injury arteries, and enhance HO-1 expression in circulating monocytes and in arteries after wire injury, suggesting the in vivo induction of HO-1 by GBE. Conclusion: GBE could inhibit cytokine-induced endothelial adhesiveness by inducing HO-1 expression via the activation of p38 and Nrf-2 pathways, a mechanism in which oxidative stress is not directly involved. GBE might exert its anti-atherogenesis and vascular protective effects by inducing vascular HO-1 expression.

KW - Antioxidant

KW - Atherogenesis

KW - Endothelial cells

KW - Ginkgo biloba extract

KW - Heme oxygenase-1

KW - Nrf-2

KW - Wire injury

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