Thymol reduces oxidative stress, aortic intimal thickening, and inflammation-related gene expression in hyperlipidemic rabbits

Ya-Mei Yu, Tzu-Yu Chao, Weng-Cheng Chang, Margaret J Chang, Ming-Fen Lee, Ya-Mei Yu, Tzu-Yu Chao, Weng-Cheng Chang, Margaret J Chang, Ming-Fen Lee

Abstract

Atherosclerosis plays a key role in the development of cardiovascular diseases, and is often associated with oxidative stress and local inflammation. Thymol, a major polyphenolic compound in thyme, exhibits antioxidant and anti-inflammatory properties. In this study, we measured the in vitro antioxidant activity of thymol, and investigated the effect of thymol on high-fat-diet-induced hyperlipidemia and atherosclerosis. New Zealand white rabbits were fed with regular chow, high-fat and high-cholesterol diet (HC), T3, or T6 (HC with thymol supplementation at 3 mg/kg/d or 6 mg/kg/d, respectively) for 8 weeks. Aortic intimal thickening, serum lipid parameters, multiple inflammatory markers, proinflammatory cytokines, and atherosclerosis-associated indicators were significantly increased in the HC group but decreased upon thymol supplementation. In summary, thymol exhibits antioxidant activity, and may suppress the progression of high-fat-diet-induced hyperlipidemia and atherosclerosis by reducing aortic intimal lipid lesion, lowering serum lipids and oxidative stress, and alleviating inflammation-related responses.

Keywords: antioxidant; atherosclerosis; inflammatory markers; oxidative stress; thymol.

Conflict of interest statement

Conflicts of interest

The authors declare no conflicts of interest.

Copyright © 2016. Published by Elsevier B.V.

Figures

Figure 1
Figure 1
(A) Effect of thymol on thoracic aortic intimal thickening in New Zealand white rabbits. In the control (normal diet) group (N), rabbits were fed with regular rabbit chow; in the high-fat and high-cholesterol diet group (HC), rabbits were fed with rabbit chow plus 10% lard and 1% cholesterol; in the T3 and T6 groups, rabbits were fed as the HC group but also supplemented with 3 mg/kg/d and 6 mg/kg/d of thymol, respectively (magnification: 100×). (B) The percentage of lipid lesion was calculated; all data were expressed as mean ± standard deviation; p < 0.05 was used as the threshold for statistical significance (n = 6). *p < 0.05 as compared with the N group; **p < 0.05 as compared with the HC group. I = intima; M = media. T3 = HC supplemented with thymol 3 mg/kg/d; T6 = HC supplemented with thymol 6 mg/kg/d.
Figure 2
Figure 2
Effect of thymol on gene expression of (A) vascular cell adhesion molecule-1 (VCAM-1), (B) monocyte chemotactic protein-1 (MCP-1), and (C) matrix metalloproteinase-9 (MMP-9). All data were expressed as mean ± standard deviation; p < 0.05 was used as the threshold for statistical significance (n = 6). *p < 0.05 as compared with the normal diet (N) group; **p < 0.05 as compared with the high-fat high-cholesterol group (HC). T3 = HC supplemented with thymol 3 mg/kg/d; T6 = HC supplemented with thymol 6 mg/kg/d.
Figure 3
Figure 3
Effect of thymol on gene expression of (A) interleukin-1β (IL-1β), (B) IL-6, (C) tumor necrosis factor-α (TNF-α), and (D) TNF-β. All data were expressed as mean ± standard deviation; p < 0.05 was used as the threshold for statistical significance (n = 6). *p < 0.05 as compared with the normal diet (N) group; **p < 0.05 as compared with the high-fat high-cholesterol group (HC). T3 = HC supplemented with thymol 3 mg/kg/d; T6 = HC supplemented with thymol 6 mg/kg/d.

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