The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells

  • Ran, Xiaoli (Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College) ;
  • Zhao, Wenwen (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau) ;
  • Li, Wenping (Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College) ;
  • Shi, Jingshan (Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College) ;
  • Chen, Xiuping (State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau)
  • Received : 2015.01.09
  • Accepted : 2015.06.02
  • Published : 2016.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha ($TNF-{\alpha}$) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of $TNF-{\alpha}$ on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe $CM-DCFH_2-DA$. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. $TNF-{\alpha}$ induced LOX-1 expression in a dose- and time- dependent manner in endothelial cells. $TNF-{\alpha}$ induced ROS formation, phosphorylation of $NF-{\kappa}B$ p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. $NF-{\kappa}B$ inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited $TNF-{\alpha}-induced$ LOX-1 expression. CPT and NAC suppressed $TNF-{\alpha}-induced$ LOX-1 expression and phosphorylation of $NF-{\kappa}B$ p65 and ERK in rat aorta. These data suggested that $TNF-{\alpha}$ induced LOX-1 expression via ROS activated $NF-{\kappa}B/ERK$ pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.

Keywords

References

  1. Yagi A, Fujimoto K, Tanonaka K, Hirai K, Takeo S. Possible active components of tan-shen (Salvia miltiorrhiza) for protection of the myocardium against ischemia-induced derangements. Planta Med. 1989;55:51-54. https://doi.org/10.1055/s-2006-961824
  2. Ma S, Yang D, Wang K, Tang B, Li D, Yang Y. Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2. Mol Med Rep. 2012;6:145-150.
  3. Jin HJ, Xie XL, Ye JM, Li CG. TanshinoneIIA and cryptotanshinone protect against hypoxia-induced mitochondrial apoptosis in H9c2 cells. PLoS One. 2013;8:e51720. https://doi.org/10.1371/journal.pone.0051720
  4. Suh SJ, Jin UH, Choi HJ, Chang HW, Son JK, Lee SH, Jeon SJ, Son KH, Chang YC, Lee YC, Kim CH. Cryptotanshinone from Salvia miltiorrhiza BUNGE has an inhibitory effect on TNF-alphainduced matrix metalloproteinase-9 production and HASMC migration via down-regulated NF-kappaB and AP-1. Biochem Pharmacol. 2006;72:1680-1689. https://doi.org/10.1016/j.bcp.2006.08.013
  5. Zhou Z, Wang SQ, Liu Y, Miao AD. Cryptotanshinone inhibits endothelin-1 expression and stimulates nitric oxide production in human vascular endothelial cells. Biochim Biophys Acta. 2006;1760:1-9. https://doi.org/10.1016/j.bbagen.2005.09.009
  6. Jin YC, Kim CW, Kim YM, Nizamutdinova IT, Ha YM, Kim HJ, Seo HG, Son KH, Jeon SJ, Kang SS, Kim YS, Kam SC, Lee JH, Chang KC. Cryptotanshinone, a lipophilic compound of Salvia miltiorrriza root, inhibits TNF-alpha-induced expression of adhesion molecules in HUVEC and attenuates rat myocardial ischemia/reperfusion injury in vivo. Eur J Pharmacol. 2009; 614:91-97. https://doi.org/10.1016/j.ejphar.2009.04.038
  7. Ang KP, Tan HK, Selvaraja M, Kadir AA, Somchit MN, Akim AM, Zakaria ZA, Ahmad Z. Cryptotanshinone attenuates in vitro oxLDL-induced pre-lesional atherosclerotic events. Planta Med. 2011;77:1782-1787. https://doi.org/10.1055/s-0030-1271119
  8. Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T. An endothelial receptor for oxidized low-density lipoprotein. Nature. 1997;386:73-77. https://doi.org/10.1038/386073a0
  9. Chen XP, Zhang TT, Du GH. Lectin-like oxidized low-density lipoprotein receptor-1, a new promising target for the therapy of atherosclerosis? Cardiovasc Drug Rev. 2007;25:146-161. https://doi.org/10.1111/j.1527-3466.2007.00009.x
  10. Renier G. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a relevant target for diabetic vasculopathy? Cardiovasc Hematol Disord Drug Targets. 2008;8:203-211. https://doi.org/10.2174/187152908785849107
  11. Ulrich-Merzenich G, Zeitler H. The lectin-like oxidized low- density lipoprotein receptor-1 as therapeutic target for atherosclerosis, inflammatory conditions and longevity. Expert Opin Ther Targets. 2013;17:905-919. https://doi.org/10.1517/14728222.2013.805748
  12. Chen XP, DU GH. Lectin-like oxidized low-density lipoprotein receptor-1: protein, ligands, expression and pathophysiological significance. Chin Med J (Engl). 2007;120:421-426.
  13. Kume N, Murase T, Moriwaki H, Aoyama T, Sawamura T, Masaki T, Kita T. Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res. 1998;83:322-327. https://doi.org/10.1161/01.RES.83.3.322
  14. Moriwaki H, Kume N, Kataoka H, Murase T, Nishi E, Sawamura T, Masaki T, Kita T. Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages: upregulated expression by TNF-alpha. FEBS Lett. 1998;440:29-32. https://doi.org/10.1016/S0014-5793(98)01414-8
  15. Kume N, Moriwaki H, Kataoka H, Minami M, Murase T, Sawamura T, Masaki T, Kita T. Inducible expression of LOX-1, a novel receptor for oxidized LDL, in macrophages and vascular smooth muscle cells. Ann N Y Acad Sci. 2000;902:323-327.
  16. Chiba Y, Ogita T, Ando K, Fujita T. PPARgamma ligands inhibit TNF-alpha-induced LOX-1 expression in cultured endothelial cells. Biochem Biophys Res Commun. 2001;286:541-546. https://doi.org/10.1006/bbrc.2001.5361
  17. Shibata Y, Kume N, Arai H, Hayashida K, Inui-Hayashida A, Minami M, Mukai E, Toyohara M, Harauma A, Murayama T, Kita T, Hara S, Kamei K, Yokode M. Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB (NF-kappaB) activation and lectin-like oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells. Atherosclerosis. 2007;193:20-27. https://doi.org/10.1016/j.atherosclerosis.2006.08.011
  18. Lee MJ, Lee HS, Park SD, Moon HI, Park WH. Leonurus sibiricus herb extract suppresses oxidative stress and ameliorates hypercholesterolemia in C57BL/6 mice and TNF-alpha induced expression of adhesion molecules and lectin-like oxidized LDL receptor-1 in human umbilical vein endothelial cells. Biosci Biotechnol Biochem. 2010;74:279-284. https://doi.org/10.1271/bbb.90582
  19. Song G, Tian H, Liu J, Zhang H, Sun X, Qin S. H2 inhibits TNF-${\alpha}$-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor ${\kappa}$B activation in endothelial cells. Biotechnol Lett. 2011;33:1715-1722. https://doi.org/10.1007/s10529-011-0630-8
  20. Yamagata K, Tusruta C, Ohtuski A, Tagami M. Docosahexaenoic acid decreases TNF-${\alpha}$-induced lectin-like oxidized low-density lipoprotein receptor-1 expression in THP-1 cells. Prostaglandins Leukot Essent Fatty Acids. 2014;90:125-132. https://doi.org/10.1016/j.plefa.2013.12.011
  21. Chen X, Zhong Z, Xu Z, Chen L, Wang Y. No protective effect of curcumin on hydrogen peroxide-induced cytotoxicity in HepG2 cells. Pharmacol Rep. 2011;63:724-732. https://doi.org/10.1016/S1734-1140(11)70584-9
  22. Chen X, Zhong Z, Xu Z, Chen L, Wang Y. 2',7'-Dichlorodihydr ofluorescein as a fluorescent probe for reactive oxygen species measurement: Forty years of application and controversy. Free Radic Res. 2010;44:587-604. https://doi.org/10.3109/10715761003709802
  23. Zhang T, Huang Z, Dai Y, Chen X, Zhu P, Du G. The expression of recombinant human LOX-1 and identifying its mimic ligands by fluorescence polarization-based high throughput screening. J Biotechnol. 2006;125:492-502. https://doi.org/10.1016/j.jbiotec.2006.03.040
  24. Chen X, Andresen BT, Hill M, Zhang J, Booth F, Zhang C. Role of reactive oxygen species in tumor necrosis factor-alpha induced endothelial dysfunction. Curr Hypertens Rev. 2008;4:245-255. https://doi.org/10.2174/157340208786241336
  25. Zhang H, Park Y, Wu J, Chen Xp, Lee S, Yang J, Dellsperger KC, Zhang C. Role of TNF-alpha in vascular dysfunction. Clin Sci (Lond). 2009;116:219-230. https://doi.org/10.1042/CS20080196
  26. Dunn S, Vohra RS, Murphy JE, Homer-Vanniasinkam S, Walker JH, Ponnambalam S. The lectin-like oxidized low- density-lipoprotein receptor: a pro-inflammatory factor in vascular disease. Biochem J. 2008;409:349-355. https://doi.org/10.1042/BJ20071196
  27. Liang M, Zhang P, Fu J. Up-regulation of LOX-1 expression by TNF-alpha promotes trans-endothelial migration of MDA- MB-231 breast cancer cells. Cancer Lett. 2007;258:31-37. https://doi.org/10.1016/j.canlet.2007.08.003
  28. Chen X, Zhang H, McAfee S, Zhang C. The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice. Am J Physiol Heart Circ Physiol. 2010;299:H605-612. https://doi.org/10.1152/ajpheart.01096.2009
  29. Nagase M, Ando K, Nagase T, Kaname S, Sawamura T, Fujita T. Redox-sensitive regulation of lox-1 gene expression in vascular endothelium. Biochem Biophys Res Commun. 2001;281:720-725. https://doi.org/10.1006/bbrc.2001.4374
  30. Sun Y, Chen X. Ox-LDL-induced LOX-1 expression in vascular smooth muscle cells: role of reactive oxygen species. Fundam Clin Pharmacol. 2011;25:572-579. https://doi.org/10.1111/j.1472-8206.2010.00885.x
  31. Pirillo A, Reduzzi A, Ferri N, Kuhn H, Corsini A, Catapano AL. Upregulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) by 15-lipoxygenase-modified LDL in endothelial cells. Atherosclerosis. 2011;214:331-337. https://doi.org/10.1016/j.atherosclerosis.2010.11.006
  32. Li L, Sawamura T, Renier G. Glucose enhances endothelial LOX-1 expression: role for LOX-1 in glucose-induced human monocyte adhesion to endothelium. Diabetes. 2003;52:1843-1850. https://doi.org/10.2337/diabetes.52.7.1843
  33. Fu R, Yan T, Wang Q, Guo Q, Yao H, Wu X, Li Y. Suppression of endothelial cell adhesion by XJP-1, a new phenolic compound derived from banana peel. Vascul Pharmacol. 2012;57:105-112. https://doi.org/10.1016/j.vph.2012.05.006
  34. Lee WY, Liu KW, Yeung JH. Reactive oxygen species-mediated kinase activation by dihydrotanshinone in tanshinones-induced apoptosis in HepG2 cells. Cancer Lett. 2009;285:46-57. https://doi.org/10.1016/j.canlet.2009.04.040
  35. Chen W, Liu L, Luo Y, Odaka Y, Awate S, Zhou H, Shen T, Zheng S, Lu Y, Huang S. Cryptotanshinone activates p38/JNK and inhibits Erk1/2 leading to caspase-independent cell death in tumor cells. Cancer Prev Res (Phila). 2012;5:778-787. https://doi.org/10.1158/1940-6207.CAPR-11-0551
  36. Mukai E, Kume N, Hayashida K, Minami M, Yamada Y, Seino Y, Kita T. Heparin-binding EGF-like growth factor induces expression of lectin-like oxidized LDL receptor-1 in vascular smooth muscle cells. Atherosclerosis. 2004;176:289-296. https://doi.org/10.1016/j.atherosclerosis.2004.03.028
  37. Li L, Sawamura T, Renier G. Glucose enhances human macrophage LOX-1 expression: role for LOX-1 in glucose-induced macrophage foam cell formation. Circ Res. 2004;94:892-901. https://doi.org/10.1161/01.RES.0000124920.09738.26
  38. Liu Z, Xu S, Huang X, Wang J, Gao S, Li H, Zhou C, Ye J, Chen S, Jin ZG, Liu P. Cryptotanshinone, an orally bioactive herbal compound from Danshen, attenuates atherosclerosis in apolipoprotein E-deficient mice: role of lectin-like oxidized LDL receptor-1 (LOX-1). Br J Pharmacol. 2015. doi: 10.1111/bph.13068. [Epub ahead of print]

Cited by

  1. Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics vol.39, pp.5, 2018, https://doi.org/10.1038/aps.2017.193
  2. Targeting LOX‐1 in atherosclerosis and vasculopathy: current knowledge and future perspectives vol.1443, pp.1, 2016, https://doi.org/10.1111/nyas.13984
  3. Sarpogrelate and rosuvastatin synergistically ameliorate aortic damage induced by hyperlipidemia in apolipoprotein E-deficient mice vol.20, pp.6, 2016, https://doi.org/10.3892/etm.2020.9300