Inhibitory effect of paeonol on aortic endothelial inflammation in atherosclerotic rats by up-regulation of caveolin-1 expression and suppression of NF-κB pathway

LIU Ya-rong1,2 SHAO Qian1 ZHANG Hui-hui1 JIA Ying1 DAI Min1,2

(1.Department of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China 230012)
(2.Key Laboratory of Xin’an Medicine, Hefei, Anhui, China 230012)

【Abstract】To explore whether paeonol can play an anti-atherosclerotic role by regulating the expression of aortic caveolin-1 and affecting NF-κB pathway, so as to inhibit the inflammatory response of vascular endothelium in atherosclerotic rats. The atherosclerotic model of rats was induced by high-fat diet and vitamin D2. The primary culture of vascular endothelial cells (VECs) was carried out by tissue block pre-digestion and adherent method. The injury model of VECs was induced by lipopolysaccharide (LPS), and filipin, a small caveolin inhibitor, was added for control. HE staining was used to observe pathological changes of aorta. TNF-α, IL-6 and VCAM-1 were detected by ELISA. Western blot assay was used to detect the protein expression levels of caveolin-1 and p65 in aorta and VECs. The results showed that as compared with model group, paeonol significantly reduced aortic plaque area and lesion degree in rats, decreased the level of serum TNF-α, IL-6 and VCAM-1 in the rats and enhanced the relative expression level of caveolin-1, decreased p65 expression conversely (P < 0.05 or P < 0.01). In vitro, as compared with model group, paeonol obviously improved cell morphology, decreased the secretion of TNF-α, IL-6 and VCAM-1 in VECs, increased caveolin-1 expression, and decreased p65 protein expression (P < 0.05 or P < 0.01). Furthermore, filipin could reverse the effect of paeonol on expression of inflammatory factors and proteins (P < 0.05 or P < 0.01). According to the results, it was found that paeonol could play the role of anti-atherosclerosis by up-regulating the expression of caveolin-1 and inhibiting the activation of NF-κB pathway to reduce vascular inflammation in atherosclerotic rats.

【Keywords】 caveolin-1; paeonol; atherosclerosis; aorta; vascular endothelial cell; inflammation;


【Funds】 National Natural Science Foundation of China (81773937) Natural Science Research Project of Anhui University of Traditional Chinese Medicine (2018zrd06)

Download this article


    [1] YE Y, NYLANDER S, BIRNBAUM Y. Unraveling the interaction of aspirin, ticagrelor, and rosuvastatin on the progression of atherosclerosis and inflammation in diabetic mice [J]. Cardiovasc Drug Ther, 2017, 31 (5/6): 489.

    [2] WANG D, WANG Y. Advances in animal models of atherosclerosis [J]. Chinese Heart Journal, 2018, 30 (4): 490 (in Chinese).

    [3] CHU X M, LI B, AN Y, et al. The progression of the relation between inflammation and atherosclerosis [J]. Molecular Cardiology of China, 2010, 11 (3): 184 (in Chinese).

    [4] LIAO D F, QIN L. Caveolae and caveolin-1: a possible platform of reverse cholesterol transport and inflammation in atherosclerosis [J]. Chinese Journal of Arteriosclerosis, 2012, 20 (5): 385 (in Chinese).

    [5] RODRIGUEZ-FEO J A, HELLINGS W E, MOLL F L, et al. Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease [J]. PLoS ONE, 2008, 3 (7): e2612.

    [6] YANG C, LIU X Z, et al. Advance of caveolin-1 in atherosclerosis. [J]. Hainan Medical Journal, 2013, 24 (3): 437 (in Chinese).

    [7] LI H KDAI M, WANG D L. Establishment of atherosclerotic model in rabbits and experimental study on paeonol action [J]. Chinese Journal of Traditional Medical Science and Technology, 2005, 12 (3): 129 (in Chinese).

    [8] LIU Y R, LI C, WU H F, et al. Paeonol attenuated inflammatory response of endothelial cells via stimulating monocytes-derived exosomal microRNA-223 [J]. Front Pharmacol, 2018, 9: 1105.

    [9] ZHANG W Z, LI G Y, QI Q, et al. Regulatory effect of Di′ao Xinxuekang on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats [J]. China Journal of Chinese Materia Medica, 2020, 45 (3): 602 (in Chinese).

    [10] WU J K, YANG Q, LI Y Y, et al. Effect of leech on VSMCs in early atherosclerosis rats via p38MAPK signaling pathway [J]. China Journal of Chinese Materia Medica, 2017, 42 (16): 3191 (in Chinese).

    [11] FERNANDEZ-HERNANDO C, YU J, DAVALOS A, et al. Endothelial-specific overexpression of caveolin-1 accelerates atherosclerosis in apolipoprotein E-deficient mice [J]. Am J Pathol, 2011, 177 (2): 998.

    [12] LI Z L, XU G, LEI M, et al. Effect of niacin on caveolin-1 expression in adipose tissue of hypercholesterolemic rabbits [J]. The Journal of Practical Medicine, 2012, 26 (6): 893 (in Chinese).

    [13] YAO H Z. 加减活络效灵丹对糖尿病大鼠动脉硬化形成早期的干预作用 [D]. Beijing: Beijing University of Chinese Medicine, 2016 (in Chinese).

    [14] LUO X L, ZHONG H, LIANG X, et al. Mechanisms of caveolin-1 up-regulating the extracellular Ca2+-sensing receptor mediated endothelial nitric oxide synthetase activation in human umbilical vein endothelial cells [J]. Chinese Journal of Arteriosclerosis, 2013, 21 (6): 486 (in Chinese).

    [15] YUE W, YAO S T, ZHOU X, et al. Inhibitory effect of caveolin-1 on endoplasmic reticulum stress-induced apoptosis in macrophages via p38 MAPK pathway [J]. Acta Physiologica Sinica, 2012, 64 (2): 149 (in Chinese).

    [16] JOHN H, CHIDLOW J, WILLIAM C S. Caveolae, caveolins, and cavins: complex control of cellular signaling and inflammation [J]. Cardiovasc Res, 2010, 86 (2): 219.

    [17] HU G, YE R D, DINAUER M C, et al. Neutrophil caveolin-1 expression contributes to mechanism of lung inflammation and injury [J]. Am J Physiol Lung Cell Mol Physiol, 2008, 294: 178.

    [18] WANG X M, KIM H P, NAKAHIRA K, et al. The heme oxygenase-1/carbonmonoxide pathway suppresses TLR4 signaling by regulating the interaction of TLR4 with caveolin-1 [J]. J Immunol, 2009, 182 (6): 809.

    [19] GARREAN S, GAO X P, BROVKOVYCH V, et al. Caveolin-1 regulates NF-kappa B activation and lung inflammatory response to sepsis induced by lipopolysaccharide [J]. J Immunol, 2006, 177 (7): 853.

    [20] XIE X M, LI C, SUN Y, et al. Paeonol reduces exosome secretion in LPS-induced THP-1 cells by inhibiting p38MAPK/N-SMase2 pathway [J]. Chinese Journal of Arteriosclerosis, 2019, 27 (1): 11 (in Chinese).

    [21] SONG A W, WU H F, DAI M. Paeonol attenuates progression of atherosclerotic lesion formation through lipid regulation, anti-inflammatory and antioxidant activities [J]. J Pharm Sci-US, 2018, 27 (8): 565.

    [22] LIU Y R, WU H F, DAI M, et al. Effects of paeonol on the release of tumor necrosis factor-α from vascular endothelial cells with lipopolysaccharide-induced injury and the apoptosis of vascular smooth muscle cells in a co-culture system and its influence on the p38MAPK signaling pathway [J]. Journal of Anhui University of Chinese Medicine, 2018, 37 (4): 65 (in Chinese).

    [23] HU W J, ZHANG Z, DAI M, et al. Paeonol affects proliferation activity of rat vasular endothelial cells induced by lipopolysaccharide and co-cultured with smooth muscle cells via inhibiting pathway of PI3K/AKT-NF-κB signaling [J]. China Journal of Chinese Materia Medica, 2016, 41 (12): 2298 (in Chinese).

This Article



Vol 45, No. 11, Pages 2578-2585

June 2020


Article Outline



  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References