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Paeonol Inhibits the Proliferation, Invasion, and Inflammatory Reaction Induced by TNF-α in Vascular Smooth Muscle Cells

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Abstract

The aim of this study was to evaluate the effect of paeonol on the proliferation, migration, and inflammation induced by tumor necrosis factor (TNF-α) of rat vascular smooth muscle cells (VSMCs). Primary rat VSMCs were identified by immunofluorescence assay. The inhibition of VSMCs proliferation induced by TNF-α was observed after paeonol treatment in a dose-dependent manner. Treatment with 100 μM paeonol significantly reduced the expression of proliferating cell nuclear antigen (PCNA). On the other hand, transwell assay showed that treatment with paeonol suppressed the invasion of TNF-α-induced VSMCs and the production of inflammation factors stimulated by TNF-α. For apoptosis induced by paeonol, Western blot analysis showed that cleaved caspase-3 and -9 were detected, and pro-apoptotic protein Bax was up-regulated, whereas anti-apoptotic protein Bcl-2 was down-regulated by paeonol in TNF-α-stimulated VSMCs. ELISA analysis data showed that both levels of IL-1β and IL-6 produced by the stimulation of TNF-α were decreased by paeonol in a dose-dependent manner in VSMCs. These results suggest that paeonol can effectively inhibit the proliferation through apoptotic induction through caspase pathway in VSMCs induced by TNF-α. Also, paeonol significantly reduced the invasion and the inflammation stimulated by TNF-α in VSMCs.

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References

  1. Lusis, A. J. (2000). Atherosclerosis. Nature, 407, 233–241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Doran, A. C., Meller, N., & McNamara, C. A. (2008). Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology, 28, 812–819.

    Article  CAS  Google Scholar 

  3. Williams KJ, Tabas I. (1999). Atherosclerosis–an inflammatory disease. The New England Journal of Medicine, 340, 1928; author reply 1929.

  4. Newby, A. C., & Zaltsman, A. B. (1999). Fibrous cap formation or destruction—the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation. Cardiovascular Research, 41, 345–360.

    Article  CAS  PubMed  Google Scholar 

  5. Liu, M. H., Lin, A. H., Lee, H. F., Ko, H. K., Lee, T. S., & Kou, Y. R. (2014). Paeonol attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling. Mediators of Inflammation, 2014, 651890.

    PubMed  PubMed Central  Google Scholar 

  6. Cai, J., Chen, S., Zhang, W., Hu, S., Lu, J., Xing, J., & Dong, Y. (2014). Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating the expression of transgelin 2. Phytomedicine, 21, 984–991.

    Article  CAS  PubMed  Google Scholar 

  7. Liu, J., Wang, S., Feng, L., Ma, D., Fu, Q., Song, Y., & Ma, S. (2013). Hypoglycemic and antioxidant activities of paeonol and its beneficial effect on diabetic encephalopathy in streptozotocin-induced diabetic rats. Journal of Medicinal Food, 16, 577–586.

    Article  CAS  PubMed  Google Scholar 

  8. Hsieh, C. L., Cheng, C. Y., Tsai, T. H., Lin, I. H., Liu, C. H., Chiang, S. Y., & Tang, N. Y. (2006). Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemia-reperfusion injured rats. Journal of Ethnopharmacology, 106, 208–215.

    Article  CAS  PubMed  Google Scholar 

  9. Chou, T. C. (2003). Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia. British Journal of Pharmacology, 139, 1146–1152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dai, M., Zhi, X., Peng, D., & Liu, Q. (1999). Inhibitory effect of paeonol on experimental atherosclerosis in quails. China Journal of Chinese Materia Medica, 24(488–490), 512.

    Google Scholar 

  11. Pan, L. L., & Dai, M. (2009). Paeonol from Paeonia suffruticosa prevents TNF-alpha-induced monocytic cell adhesion to rat aortic endothelial cells by suppression of VCAM-1 expression. Phytomedicine, 16, 1027–1032.

    Article  CAS  PubMed  Google Scholar 

  12. Wang, X., Zhu, G., Yang, S., Cheng, H., Wang, F., Li, X., & Li, Q. (2011). Paeonol prevents excitotoxicity in rat pheochromocytoma PC12 cells via downregulation of ERK activation and inhibition of apoptosis. Planta Medica, 77, 1695–1701.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou, J., Zhou, L., Hou, D., Tang, J., Sun, J., & Bondy, S. C. (2011). Paeonol increases levels of cortical cytochrome oxidase and vascular actin and improves behavior in a rat model of Alzheimer’s disease. Brain Research, 1388, 141–147.

    Article  CAS  PubMed  Google Scholar 

  14. Lei, Y., Li, H. X., Jin, W. S., Peng, W. R., Zhang, C. J., Bu, L. J., & Sun, G. P. (2013). The radiosensitizing effect of Paeonol on lung adenocarcinoma by augmentation of radiation-induced apoptosis and inhibition of the PI3K/Akt pathway. International Journal of Radiation Biology, 89, 1079–1086.

    Article  CAS  PubMed  Google Scholar 

  15. Yin, J., Wu, N., Zeng, F., Cheng, C., Kang, K., & Yang, H. (2013). Paeonol induces apoptosis in human ovarian cancer cells. Acta Histochemica, 115, 835–839.

    Article  CAS  PubMed  Google Scholar 

  16. Li, M., Tan, S. Y., & Wang, X. F. (2014). Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE(2) synthesis and COX-2 expression. Oncology Reports, 32, 2845–2853.

    CAS  PubMed  Google Scholar 

  17. Willis, S. N., & Adams, J. M. (2005). Life in the balance: how BH3-only proteins induce apoptosis. Current Opinion in Cell Biology, 17, 617–625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Price, J. T., & Thompson, E. W. (2002). Mechanisms of tumour invasion and metastasis: Emerging targets for therapy. Expert opinion on therapeutic targets, 6, 217–233.

    Article  CAS  PubMed  Google Scholar 

  19. Chen, N., Liu, D., Soromou, L. W., Sun, J., Zhong, W., Guo, W., & Feng, H. (2014). Paeonol suppresses lipopolysaccharide-induced inflammatory cytokines in macrophage cells and protects mice from lethal endotoxin shock. Fundamental & Clinical Pharmacology, 28, 268–276.

    Article  CAS  Google Scholar 

  20. Wang, J. C., & Bennett, M. (2012). Aging and atherosclerosis: Mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circulation Research, 111, 245–259.

    Article  CAS  PubMed  Google Scholar 

  21. Lutgens, E., de Muinck, E. D., Kitslaar, P. J., Tordoir, J. H., Wellens, H. J., & Daemen, M. J. (1999). Biphasic pattern of cell turnover characterizes the progression from fatty streaks to ruptured human atherosclerotic plaques. Cardiovascular Research, 41, 473–479.

    Article  CAS  PubMed  Google Scholar 

  22. Dai, M., Liu, Q. Y., Gu, C. G., & Zhang, H. Y. (2000). Inhibitory effect of paeonol on lipid peroxidational reaction and oxidational decorate of low density lipoprotein. China Journal of Chinese Materia Medica, 25, 625–627.

    CAS  PubMed  Google Scholar 

  23. Chen, J., Dai, M., & Wang, Y. (2014). Paeonol inhibits proliferation of vascular smooth muscle cells stimulated by high glucose via Ras-Raf-ERK1/2 signaling pathway in coculture model. Evidence-Based Complementary and Alternative Medicine, 2014, 484269.

    PubMed  PubMed Central  Google Scholar 

  24. Wang, Y. Q., Dai, M., Zhong, J. C., & Yin, D. K. (2012). Paeonol inhibits oxidized low density lipoprotein-induced monocyte adhesion to vascular endothelial cells by inhibiting the mitogen activated protein kinase pathway. Biological & Pharmaceutical Bulletin, 35, 767–772.

    Article  CAS  Google Scholar 

  25. Galkina, E., & Ley, K. (2009). Immune and inflammatory mechanisms of atherosclerosis (*). Annual Review of Immunology, 27, 165–197.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Li, N., Fan, L. L., Sun, G. P., Wan, X. A., Wang, Z. G., Wu, Q., & Wang, H. (2010). Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo. World Journal of Gastroenterology, 16, 4483–4490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Adams, J. M. (2003). Ways of dying: Multiple pathways to apoptosis. Genes & Development, 17, 2481–2495.

    Article  CAS  Google Scholar 

  28. Bennett, M. R., Evan, G. I., & Schwartz, S. M. (1995). Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. The Journal of Clinical Investigation, 95, 2266–2274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ou, Y., Li, Q., Wang, J., Li, K., & Zhou, S. (2014). Antitumor and apoptosis induction effects of paeonol on mice bearing EMT6 breast carcinoma. Biomolecules & Therapeutics, 22, 341–346.

    Article  CAS  Google Scholar 

  30. Yin, S., Wang, R., Zhou, F., Zhang, H., & Jing, Y. (2011). Bcl-xL is a dominant antiapoptotic protein that inhibits homoharringtonine-induced apoptosis in leukemia cells. Molecular Pharmacology, 79, 1072–1083.

    Article  CAS  PubMed  Google Scholar 

  31. Adams, J. M., & Cory, S. (2007). The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene, 26, 1324–1337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ley, R., Ewings, K. E., Hadfield, K., & Cook, S. J. (2005). Regulatory phosphorylation of Bim: Sorting out the ERK from the JNK. Cell Death and Differentiation, 12, 1008–1014.

    Article  CAS  PubMed  Google Scholar 

  33. Itoh, Y. (2006). MT1-MMP: A key regulator of cell migration in tissue. IUBMB Life, 58, 589–596.

    Article  CAS  PubMed  Google Scholar 

  34. Feghali, C. A., & Wright, T. M. (1997). Cytokines in acute and chronic inflammation. Frontiers in Bioscience, 2, d12–d26.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Circulation, The Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, People’s Republic of China

    Liang Meng

  2. Department of Science and Education, The Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, People’s Republic of China

    Weidong Xu

  3. Admission Office, The Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, People’s Republic of China

    Lihong Guo

  4. Department of Pharmacy, The Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, People’s Republic of China

    Wenqi Ning

  5. Department of General Surgery, The Central Hospital Affiliated to Shenyang Medical College, 5 West Nanqi Road, Shenyang, 110024, People’s Republic of China

    Xiandong Zeng

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  1. Liang Meng
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Correspondence to Xiandong Zeng.

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Meng, L., Xu, W., Guo, L. et al. Paeonol Inhibits the Proliferation, Invasion, and Inflammatory Reaction Induced by TNF-α in Vascular Smooth Muscle Cells. Cell Biochem Biophys 73, 495–503 (2015). https://doi.org/10.1007/s12013-015-0686-5

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  • DOI: https://doi.org/10.1007/s12013-015-0686-5

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