TY - JOUR
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
Y1 - 2013/3/12
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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U2 - 10.1016/j.ejps.2013.01.002
DO - 10.1016/j.ejps.2013.01.002
M3 - Article
C2 - 23357604
AN - SCOPUS:84874158486
SN - 0928-0987
VL - 48
SP - 803
EP - 811
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
IS - 4-5
ER -
