Ginkgo biloba extract (GbE) enhances the anti-atherogenic effect of cilostazol by inhibiting ROS generation.

In-Hyuk Jung,Seong Keun Sonn,Dae-Yong Kim,Jong-Gil Park,So Young Lee,Hye Young Han,Ji-Young Yoo,Se-Jin Jeong,Keun Ho Ryu,You-Han Lee,Bong Yong Lee,Hang Lee,Goo Taeg Oh

doi:10.3858/emm.2012.44.5.035

Ginkgo biloba extract (GbE) enhances the anti-atherogenic effect of cilostazol by inhibiting ROS generation.

In-Hyuk Jung, Seong Keun Sonn + Show 11 more

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https://doi.org/10.3858/emm.2012.44.5.035

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Abstract

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis.

Highlights

Atherosclerosis is a chronic inflammatory disease of blood vessels characterized by slow thickening of arterial walls due to the build-up of fatty material (Chen et al, 2003; Park et al, 2008)
To determine how the anti-oxygenic effect of these two compounds affects the development of atherosclerosis, we analyzed atherosclerotic lesions in apolipoprotein E (ApoE) null mice fed a high-fat diet for 16 weeks
Mice treated with cilostazol (0.1%) and Ginkgo biloba extract (GbE) (0.08%) showed a significant reduction in the size of the atherosclerotic lesion in the aortic root (0.48 ± 0.06 mm2 vs 0.56 ± 0.05 mm2 in 0.1% cilostazol, 0.08% GbE treatment group and vehicle treatment group, respectively; P = 0.04; Figure 2A)

Summary

Introduction

Atherosclerosis is a chronic inflammatory disease of blood vessels characterized by slow thickening of arterial walls due to the build-up of fatty material (Chen et al, 2003; Park et al, 2008). During the early stages of atherosclerosis, cholesterol accumulation in the intima induces endothelial cells in the arteries to express adhesion and chemoattractant molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) (Otsuki et al, 2001; Lee et al, 2005; Yun et al, 2009). Cilostazol inhibits cytokine-induced nuclear factor-κB (NF-κB) activation via AMP-activated protein kinase activation in vascular endothelial cells (Nakamura et al, 2005; Hattori et al, 2009). Besides anti-platelet and anti-vasoconstrictive properties (Wang et al, 2003; Mohamed, 2009), cilostazol promotes cholesterol efflux by regulating. Vol 44(5), 311-318, 2012 cholesterol uptake- or efflux-related genes, such as scavenger receptors (e.g., SR-A and CD36) (Shin et al, 2004; Gomez and Qureshi, 2009) and ABCA1/ ABCG1 (Nakaya et al, 2010) in macrophages

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