Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
권호 표지
DOI QR코드

DOI QR Code

Treatment with 3-Bromo-4,5-Dihydroxybenzaldehyde Improves Cardiac Function by Inhibiting Macrophage Infiltration in Mice

  • Ji, Ningning (Department of Cardiology, Yiwu Hospital of Wenzhou Medical University (Yiwu Central Hospital)) ;
  • Lou, Honghong (Department of Cardiology, Yiwu Hospital of Wenzhou Medical University (Yiwu Central Hospital)) ;
  • Gong, Xinyan (Department of Cardiology, Yiwu Hospital of Wenzhou Medical University (Yiwu Central Hospital)) ;
  • Fu, Ting (Department of Cardiology, Yiwu Hospital of Wenzhou Medical University (Yiwu Central Hospital)) ;
  • Ni, Shimao (Department of Cardiology, Yiwu Hospital of Wenzhou Medical University (Yiwu Central Hospital))
  • Received : 2017.12.10
  • Accepted : 2018.04.10
  • Published : 2018.10.31
⟨ Previous Next ⟩

Abstract

Background and Objectives: Appropriate inflammatory response is necessary for cardiac repairing after acute myocardial infarction (MI). Three-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a potent antioxidant and natural bromophenol compound derived from red algae. Although BDB has been shown to have an anti-inflammatory effect, it remains unclear whether BDB affects cardiac remolding after MI. The aim of this study was to investigate the potential role of BDB on cardiac function recovery after MI in mice. Methods: Mice were intraperitoneally injected with BDB (100 mg/kg) or vehicle control respectively 1 hour before MI and then treated every other day. Cardiac function was monitored by transthoracic echocardiography at day 7 after MI. The survival of mice was observed for 2 weeks and hematoxylin and eosin (H&E) staining was used to determine the infarct size. Macrophages infiltration was examined by immunofluorescence staining. Enzyme-linked immunosorbent assay (ELISA) was used to test the production of cytokines associated with macrophages. The phosphorylation status of nuclear factor $(NF)-{\kappa}B$ was determined by western blot. Results: BDB administration dramatically improved cardiac function recovery, and decreased mortality and infarcted size after MI. Treatment with BDB reduced $CD68^+$ macrophages, M1 and M2 macrophages infiltration post-MI, and suppressed the secretion of pro-inflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, monocyte chemoattractant protein (MCP)-1, and IL-6 in the injured hearts. Furthermore, BDB inhibited the phosphorylation of $NF-{\kappa}B$ in the infarcted hearts. Conclusions: These data demonstrate, for the first time, that BDB treatment facilitated cardiac healing by suppressing pro-inflammatory cytokine secretion, and indicate that BDB may serve as a therapeutic agent for acute MI.

Keywords

References

  1. Aurora AB, Porrello ER, Tan W, et al. Macrophages are required for neonatal heart regeneration. J Clin Invest 2014;124:1382-92. https://doi.org/10.1172/JCI72181
  2. Maruotti N, Annese T, Cantatore FP, Ribatti D. Macrophages and angiogenesis in rheumatic diseases. Vasc Cell 2013;5:11. https://doi.org/10.1186/2045-824X-5-11
  3. Hofmann U, Frantz S. Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction. Circ Res 2015;116:354-67. https://doi.org/10.1161/CIRCRESAHA.116.304072
  4. Fan X, Xu NJ, Shi JG. Bromophenols from the red alga Rhodomela confervoides. J Nat Prod 2003;66:455-8. https://doi.org/10.1021/np020528c
  5. Li K, Li XM, Ji NY, Wang BG. Bromophenols from the marine red alga Polysiphonia urceolata with DPPH radical scavenging activity. J Nat Prod 2008;71:28-30. https://doi.org/10.1021/np070281p
  6. Kim SY, Kim SR, Oh MJ, Jung SJ, Kang SY. In vitro antiviral activity of red alga, Polysiphonia morrowii extract and its bromophenols against fish pathogenic infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus. J Microbiol 2011;49:102-6. https://doi.org/10.1007/s12275-011-1035-z
  7. Piao MJ, Kang KA, Ryu YS, et al. The red algae compound 3-bromo-4,5-dihydroxybenzaldehyde protects human keratinocytes on oxidative stress-related molecules and pathways activated by UVB irradiation. Mar Drugs 2017;15:E268. https://doi.org/10.3390/md15090268
  8. Hyun YJ, Piao MJ, Zhang R, Choi YH, Chae S, Hyun JW. Photo-protection by 3-bromo-4, 5-dihydroxybenzaldehyde against ultraviolet B-induced oxidative stress in human keratinocytes. Ecotoxicol Environ Saf 2012;83:71-8. https://doi.org/10.1016/j.ecoenv.2012.06.010
  9. Kim KC, Hyun YJ, Hewage SR, et al. 3-Bromo-4,5-dihydroxybenzaldehyde enhances the level of reduced glutathione via the Nrf2-mediated pathway in human keratinocytes. Mar Drugs 2017;15:E291. https://doi.org/10.3390/md15090291
  10. Kang NJ, Han SC, Kang HJ, et al. Anti-inflammatory effect of 3-bromo-4,5-dihydroxybenzaldehyde, a component of polysiphonia morrowii, in vivo and in vitro. Toxicol Res 2017;33:325-32. https://doi.org/10.5487/TR.2017.33.4.325
  11. Kong D, Shen Y, Liu G, et al. PKA regulatory II$\alpha$ subunit is essential for PGD2-mediated resolution of inflammation. J Exp Med 2016;213:2209-26. https://doi.org/10.1084/jem.20160459
  12. Vlasov IA, Volkov AM. Dependence of heart weight on body weight in patients with cardiovascular diseases. Fiziol Cheloveka 2004;30:62-8.
  13. Gaffney L, Warren P, Wrona EA, Fisher MB, Freytes DO. Macrophages' role in tissue disease and regeneration. Results Probl Cell Differ 2017;62:245-71.
  14. Lavine KJ, Epelman S, Uchida K, et al. Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart. Proc Natl Acad Sci U S A 2014;111:16029-34. https://doi.org/10.1073/pnas.1406508111
  15. Zhang JY, Yang Z, Fang K, Shi ZL, Ren DH, Sun J. Oleuropein prevents the development of experimental autoimmune myocarditis in rats. Int Immunopharmacol 2017;48:187-95. https://doi.org/10.1016/j.intimp.2017.05.013
  16. Speranskii AI, Kostyuk SV, Kalashnikova EA, Veiko NN. Enrichment of extracellular DNA from the cultivation medium of human peripheral blood mononuclears with genomic CpG rich fragments results in increased cell production of IL-6 and TNF-a via activation of the NF-kB signaling pathway. Biomed Khim 2016;62:331-40. https://doi.org/10.18097/pbmc20166203331
  17. Lee JC, Hou MF, Huang HW, et al. Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties. Cancer Cell Int 2013;13:55. https://doi.org/10.1186/1475-2867-13-55
  18. Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 2007;204:3037-47. https://doi.org/10.1084/jem.20070885
  19. Nahrendorf M, Swirski FK. Monocyte and macrophage heterogeneity in the heart. Circ Res 2013;112:1624-33. https://doi.org/10.1161/CIRCRESAHA.113.300890
  20. Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 2006;25:6680-4. https://doi.org/10.1038/sj.onc.1209954
  21. Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 2007;8:49-62. https://doi.org/10.1038/nrm2083
  22. Capece D, Verzella D, Tessitore A, Alesse E, Capalbo C, Zazzeroni F. Cancer secretome and inflammation: the bright and the dark sides of NF-${\kappa}B$. Semin Cell Dev Biol. 2017 [Epub ahead of print].
  23. Catrysse L, van Loo G. Inflammation and the metabolic syndrome: the tissue-specific functions of NF-${\kappa}B$. Trends Cell Biol 2017;27:417-29. https://doi.org/10.1016/j.tcb.2017.01.006
  24. Han Y, Englert JA, Yang R, Delude RL, Fink MP. Ethyl pyruvate inhibits nuclear factor-kappaB-dependent signaling by directly targeting p65. J Pharmacol Exp Ther 2005;312:1097-105.

Cited by

  1. Marine Compound 3-Bromo-4,5-dihydroxybenzaldehyde Protects Skin Cells against Oxidative Damage via the Nrf2/HO-1 Pathway vol.17, pp.4, 2019, https://doi.org/10.3390/md17040234
  2. The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models vol.7, pp.13, 2018, https://doi.org/10.14814/phy2.14137
  3. Crosstalk Between Cardiac Cells and Macrophages Postmyocardial Infarction: Insights from In Vitro Studies vol.27, pp.5, 2018, https://doi.org/10.1089/ten.teb.2020.0198