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Open AccessArticle

Anti-Atherosclerotic Effect of Hibiscus Leaf Polyphenols against Tumor Necrosis Factor-alpha-Induced Abnormal Vascular Smooth Muscle Cell Migration and Proliferation

1
Laboratory Medicine, Antai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung County 928, Taiwan
2
Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City 0201, Taiwan
3
Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan
4
Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan
*
Authors to whom correspondence should be addressed.
Antioxidants 2019, 8(12), 620; https://doi.org/10.3390/antiox8120620
Received: 2 November 2019 / Revised: 29 November 2019 / Accepted: 3 December 2019 / Published: 5 December 2019
The proliferation and migration of vascular smooth muscle cells (VSMCs) are major events in the development of atherosclerosis following stimulation with proinflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α). Plant-derived polyphenols have attracted considerable attention in the prevention of atherosclerosis. Hibiscus leaf has been showed to inhibit endothelial cell oxidative injury, low-density lipoprotein oxidation, and foam cell formation. In this study, we examined the anti-atherosclerotic effect of Hibiscus leaf polyphenols (HLPs) against abnormal VSMC migration and proliferation in vitro and in vivo. Firstly, VSMC A7r5 cells pretreated with TNF-α were demonstrated to trigger abnormal proliferation and affect matrix metalloproteinase (MMP) activities. Non-cytotoxic doses of HLPs abolished the TNF-α-induced MMP-9 expression and cell migration via inhibiting the protein kinase PKB (also known as Akt)/activator protein-1 (AP-1) pathway. On the other hand, HLP-mediated cell cycle G0/G1 arrest might be exerted by inducing the expressions of p53 and its downstream factors that, in turn, suppress cyclin E/cdk2 activity, preventing retinoblastoma (Rb) phosphorylation and the subsequent dissociation of Rb/E2F complex. HLPs also attenuated reactive oxygen species (ROS) production against TNF-α stimulation. In vivo, HLPs improved atherosclerotic lesions, and abnormal VSMC migration and proliferation. Our data present the first evidence of HLPs as an inhibitor of VSMC dysfunction, and provide a new mechanism for its anti-atherosclerotic activity. View Full-Text
Keywords: proliferation; migration; vascular smooth muscle cells; atherosclerosis; tumor necrosis factor-alpha; Hibiscus leaf polyphenols proliferation; migration; vascular smooth muscle cells; atherosclerosis; tumor necrosis factor-alpha; Hibiscus leaf polyphenols
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Chou, C.-C.; Wang, C.-P.; Chen, J.-H.; Lin, H.-H. Anti-Atherosclerotic Effect of Hibiscus Leaf Polyphenols against Tumor Necrosis Factor-alpha-Induced Abnormal Vascular Smooth Muscle Cell Migration and Proliferation. Antioxidants 2019, 8, 620.

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