Skip to main content
SpringerLink
Log in

Myricetin protects cardiomyocytes from LPS-induced injury

Myricetin schützt Kardiomyozyten vor LPS-induzierten Verletzungen

  • Original articles
  • Published:
Herz Aims and scope Submit manuscript

Abstract

Background

Sepsis-induced cardiomyopathy is a well-known cause of mortality. Recent evidence has highlighted the important role of myricetin in anti-inflammation and anti-oxidative stress. However, little is known about its effect on endotoxin-induced cardiomyopathy. We examined the effect of myricetin on lipopolysaccharide (LPS)-induced cardiomyocyte injury and the underlying mechanisms in vitro.

Methods

mRNA expression of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha was examined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Protein expression levels of NF-κB/p65, IκB, IL-1beta, IL-6, and TNF-alpha were assesses via Western blotting. Immunofluorescence (IF) was used to determine the nuclear translocation of p65. Commercial kits were employed to detect the level of oxidative markers and to quantify NF-κB/p65 both in the cytoplasm and the nucleus. Finally, terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was performed to evaluate the apoptosis of H9c2 cardiomyocytes.

Results

The results showed that myricetin blunted the overexpression of IL-1beta, IL-6, and TNF-alpha markedly by inhibiting the NF-κB/P65 signaling pathway. Furthermore, myricetin treatment led to the downregulation of reactive oxygen species (ROS) accompanied by increased expression of superoxide dismutase and glutathione peroxidase. TUNEL-positive nuclei were rarely detected following myricetin treatment.

Conclusion

Our findings suggest that myricetin is a valuable protective agent against endotoxin-induced early inflammatory responses in H9c2 cardiomyocytes, which involves regulation of ROS and the IκB/NF-κb signaling pathway.

Zusammenfassung

Hintergrund

Die sepsisinduzierte Kardiomyopathie gehört zu den bekannten Todesursachen. Aktuelle Daten betonen die Bedeutung von Myricetin bei antientzündlichen Prozessen und antioxidativem Stress. Jedoch gibt es nur wenige Erkenntnisse zu seiner Wirkung auf die endotoxininduzierte Kardiomyopathie. Wir untersuchten nun die Wirkung von Myricetin auf lipopolysaccharid(LPS)-induzierte Kardiomyozytenläsionen und die zugrunde liegenden Mechanismen in vitro.

Methoden

Die mRNA-Expression von Interleukin(IL)-1beta, IL-6 und Tumornekrosefaktor(TNF)-alpha wurde mittels RT-qPCR („reverse transcription-quantitative polymerase chain reaction“) untersucht. Außerdem wurden die Proteinexpressionsspiegel von NF-κB/p65, IκB, IL-1beta, IL-6 und TNF-alpha mittels Westernblottest gemessen. Die Immunfluoreszenz (IF) wurde eingesetzt, um die nukleäre Translokation von p65 zu bestimmen. Kommerziell erhältliche Tests wurden verwendet, um die Werte für oxidative Marker zu ermitteln und NF-κB/p65 sowohl im Zytoplasma als auch im Nukleus zu quantifizieren. Schließlich wurde die TUNEL-Methode („terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling“) angewendet, um die Apopotose von H9c2-Kardiomyozyten zu untersuchen.

Ergebnisse

Die Ergebnisse zeigten, das Myricetin die Überexpression von IL-1beta, IL-6 und TNF-alpha deutlich durch Inhibition des NF-κB/P65-Signalwegs abschwächte. Darüber hinaus führte die Behandlung mit Myricetin zur Herunterregulierung reaktiver Oxygenspezies (ROS), begleitet von einer erhöhten Expression der Superoxiddismutase und der Glutathionperoxidase. TUNEL-positive Nuclei wurden nach Myricetinbehandlung nur selten entdeckt.

Schlussfolgerung

Den vorliegenden Ergebnissen zufolge ist Myricetin eine nützliche protektive Substanz gegen endotoxininduzierte frühe entzündliche Reaktionen bei H9c2-Kardiomyozyten, wozu auch die Regulation von ROS und des IκB/NFκb-Signalwegs gehört.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Singer M, Deutschman CS, Seymour CW et al (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315:801–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Vincent JL, Marshall JC, Namendys-Silva SA et al (2014) Assessment of the worldwide burden of critical illness: the intensive care over nations (icon) audit. Lancet Respir Med 2:380–386

    Article  PubMed  Google Scholar 

  3. Vieillard-Baron A (2011) Septic cardiomyopathy. Ann Intensive Care 1:6

    Article  PubMed  PubMed Central  Google Scholar 

  4. Marchant DJ, Boyd JH, Lin DC et al (2012) Inflammation in myocardial diseases. Circ Res 110:126–144

    Article  CAS  PubMed  Google Scholar 

  5. Sato R, Nasu M (2015) A review of sepsis-induced cardiomyopathy. J Intensive Care 3:48

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ma H, Wang X, Ha T et al (2016) Microrna-125b prevents cardiac dysfunction in polymicrobial sepsis by targeting traf6-mediated nuclear factor kappab activation and p53-mediated apoptotic signaling. J Infect Dis 214:1773–1783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yang P, Han Y, Gui L et al (2013) Gastrodin attenuation of the inflammatory response in h9c2 cardiomyocytes involves inhibition of nf-kappab and mapks activation via the phosphatidylinositol 3‑kinase signaling. Biochem Pharmacol 85:1124–1133

    Article  CAS  PubMed  Google Scholar 

  8. Planavila A, Rodriguez-Calvo R, Jove M et al (2005) Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes. Cardiovasc Res 65:832–841

    Article  CAS  PubMed  Google Scholar 

  9. Kumar A, Thota V, Dee L et al (1996) Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. J Exp Med 183:949–958

    Article  CAS  PubMed  Google Scholar 

  10. Turdi S, Han X, Huff AF et al (2012) Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy. Free Radic Biol Med 53:1327–1338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yao X, Carlson D, Sun Y et al (2015) Mitochondrial ros induces cardiac inflammation via a pathway through mtdna damage in a pneumonia-related sepsis model. PLOS ONE 10:e0139416

    Article  PubMed  PubMed Central  Google Scholar 

  12. Suliman HB, Welty-Wolf KE, Carraway M et al (2004) Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis. Cardiovasc Res 64:279–288

    Article  CAS  PubMed  Google Scholar 

  13. Sperandeo P, Martorana AM, Polissi A (2016) Lipopolysaccharide biogenesis and transport at the outer membrane of gram-negative bacteria. Biochim Biophys Acta. doi:10.1016/j.bbalip.2016.10.006

    PubMed  Google Scholar 

  14. Semwal DK, Semwal RB, Combrinck S et al (2016) A dietary molecule with diverse biological activities. Nutrients 8:90

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cho BO, Yin HH, Park SH et al (2016) Anti-inflammatory activity of myricetin from diospyros lotus through suppression of nf-kappab and stat1 activation and nrf2-mediated ho-1 induction in lipopolysaccharide-stimulated raw264.7 macrophages. Biosci Biotechnol Biochem 80:1520–1530

    Article  CAS  PubMed  Google Scholar 

  16. Ullah R, Nadeem M, Khalique A et al (2016) Nutritional and therapeutic perspectives of chia (salvia hispanica l.): a review. J Food Sci Technol 53:1750–1758

    Article  CAS  PubMed  Google Scholar 

  17. Ko SY et al (2012) Myricetin suppresses lps-induced mmp expression in human gingival fibroblasts and inhibits osteoclastogenesis by downregulating nfatc1 in rankl-induced raw 264.7 cells. Arch Oral Biol 57:1623–1632

    Article  CAS  PubMed  Google Scholar 

  18. Niu J, Wang K, Graham S et al (2011) Mcp-1-induced protein attenuates endotoxin-induced myocardial dysfunction by suppressing cardiac nf-small ka, cyrillicb activation via inhibition of ismall ka, cyrillicb kinase activation. J Mol Cell Cardiol 51:177–186

    Article  CAS  PubMed  Google Scholar 

  19. Planavila A, Redondo-Angulo I, Ribas F et al (2015) Fibroblast growth factor 21 protects the heart from oxidative stress. Cardiovasc Res 106:19–31

    Article  CAS  PubMed  Google Scholar 

  20. Alhamdi Y, Abrams ST, Cheng Z et al (2015) Circulating histones are major mediators of cardiac injury in patients with sepsis. Crit Care Med 43:2094–2103

    Article  CAS  PubMed  Google Scholar 

  21. Rudiger A, Singer M (2007) Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med 35:1599–1608

    Article  PubMed  Google Scholar 

  22. Mayr FB, Yende S, Angus DC (2014) Epidemiology of severe sepsis. Virulence 5:4–11

    Article  PubMed  Google Scholar 

  23. Fu RH, Liu SP, Chu CL et al (2013) Myricetin attenuates lipopolysaccharide-stimulated activation of mouse bone marrow-derived dendritic cells through suppression of ikk/nf-kappab and mapk signalling pathways. J Sci Food Agric 93:76–84

    Article  CAS  PubMed  Google Scholar 

  24. Wu S, Yue Y, Peng A et al (2016) Myricetin ameliorates brain injury and neurological deficits via nrf2 activation after experimental stroke in middle-aged rats. Food Funct 7:2624–2634

    Article  CAS  PubMed  Google Scholar 

  25. Qin S, Chen J, Tanigawa S et al (2013) Microarray and pathway analysis highlight nrf2/are-mediated expression profiling by polyphenolic myricetin. Mol Nutr Food Res 57:435–446

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Grants from Doctoral Scientific Research Foundation of Hubei University of Science and Technology (BK1417).

Author information

Authors and Affiliations

  1. School of Pharmacy, Hubei University of Science and Technology, 437100, Hubei Xianning, China

    S. Chen & B. Fan

Authors
  1. S. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. Fan.

Ethics declarations

Conflict of interest

S. Chen and B. Fan declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Fan, B. Myricetin protects cardiomyocytes from LPS-induced injury. Herz 43, 265–274 (2018). https://doi.org/10.1007/s00059-017-4556-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-017-4556-3

Keywords

Schlüsselwörter

Search

Navigation