Skip to main content
SpringerLink
Log in

The Falconoid Luteolin Mitigates the Myocardial Inflammatory Response Induced by High-Carbohydrate/High-Fat Diet in Wistar Rats

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Luteolin is a major component of many medicinal plants and traditional medicines. The current study aims at testing its protective effect against high-carbohydrate/high-fat (HCHF) diet-induced cardiac dysfunction in rats. Male Wistar rats were divided into six groups as follows: control group that received standard rat chow, group received HCHF diet (~ 30% carbohydrate and 42% fat) daily for 16 weeks, and four groups received HCHF diet concurrently with luteolin (10, 25, 50 or 100 mg/kg; 10% w/v suspension in 0.9% NaCl) daily from the first week by oral gavage. Body weight was measured weekly. At the end of the study, histopathological examinations of stained heart sections were carried out. Lipid profile, oxidative stress, and cardiac function biomarkers were measured. Furthermore, neurohumoral mediators and inflammatory cytokines (TNF-α, IL-18) were assigned. Results showed a significant improvement in cardiac function, tissue integrity, and a decrease in the compensatory neurohumoral mediators by luteolin 50 and 100 mg/kg. In addition, a significant (P < 0.05) decrease in collagen deposition, fibrosis percentage, lipid peroxidation, and inflammatory cells (macrophages and lymphocytes) infiltration was observed. Tested doses of luteolin decreased lipid peroxidation and elevated the endogenous antioxidant biomarkers (reduced glutathione and superoxide dismutase) significantly (P < 0.05). Finally, luteolin decreased TNF-α and IL-18 (P < 0.001) in a dose-dependent manner. It can be concluded that luteolin has a cardioprotective effect against HCHF diet-induced myocardial inflammation through antioxidant anti-inflammatory mechanisms.

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. Isomaa, B.O., P. Almgren, T. Tuomi, B. Forsén, K. Lahti, M. Nissén, M.R. Taskinen, and L. Groop. 2001. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24: 683–689.

    Article  CAS  PubMed  Google Scholar 

  2. Grundy, S.M. 2004. Obesity, metabolic syndrome, and cardiovascular disease. The Journal of Clinical Endocrinology and Metabolism 89: 2595–2600.

    Article  CAS  PubMed  Google Scholar 

  3. Ford, E.S. 2005. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: A summary of the evidence. Diabetes Care 28: 1769–1778.

    Article  PubMed  Google Scholar 

  4. Goldberg, I.J., C.M. Trent, and P.C. Schulze. 2012. Lipid metabolism and toxicity in the heart. Cell Metabolism 15: 805–812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mazumder, P.K., B.T. O'Neill, M.W. Roberts, J. Buchanan, U.J. Yun, R.C. Cooksey, S. Boudina, and E.D. Abel. 2004. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 53: 2366–2374.

    Article  CAS  PubMed  Google Scholar 

  6. Abel, E.D., S.E. Litwin, and G. Sweeney. 2008. Cardiac remodeling in obesity. Physiological Reviews 88: 389–419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ridker, P.M., N. Rifai, M. Pfeffer, F. Sacks, S. Lepage, and E. Braunwald. 2000. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 101: 2149–2153.

    Article  CAS  PubMed  Google Scholar 

  8. Blankenberg, S., L. Tiret, C. Bickel, D. Peetz, F. Cambien, J. Meyer, and H.J. Rupprecht. 2002. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation 106: 24–30.

    Article  CAS  PubMed  Google Scholar 

  9. Giugliano, D., A. Ceriello, and K. Esposito. 2006. The effects of diet on inflammation: Emphasis on the metabolic syndrome. Journal of the American College of Cardiology 48: 677–685.

    Article  CAS  PubMed  Google Scholar 

  10. Zheng, C.D., Y.Q. Duan, J.M. Gao, and Z.G. Ruan. 2010. Screening for anti-lipase properties of 37-traditional Chinese medicinal herbs. Journal of the Chinese Medical Association 73: 319–324.

    Article  CAS  PubMed  Google Scholar 

  11. Shang, X., H. Pan, M. Li, X. Miao, and H. Ding. 2011. Lonicera japonica Thunb.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine. Journal of Ethnopharmacology 138: 1–21.

    Article  CAS  PubMed  Google Scholar 

  12. Sonoda, M., T. Nishiyama, Y. Matsukawa, and M. Moriyasu. 2004. Cytotoxic activities of flavonoids from two Scutellaria plants in Chinese medicine. Journal of Ethnopharmacology 91: 65–68.

    Article  CAS  PubMed  Google Scholar 

  13. Hsiao, W.W., and L. Liu. 2010. The role of traditional Chinese herbal medicines in cancer therapy—From TCM theory to mechanistic insights. Planta Medica 76: 1118–1131.

    Article  CAS  PubMed  Google Scholar 

  14. Tan, B.K., and J. Vanitha. 2004. Immunomodulatory and antimicrobial effects of some traditional Chinese medicinal herbs: A review. Current Medicinal Chemistry 11: 1423–1430.

    Article  CAS  PubMed  Google Scholar 

  15. Yang, M., J. Sun, Z. Lu, G. Chen, S. Guan, X. Liu, B. Jiang, M. Ye, and D.A. Guo. 2009. Phytochemical analysis of traditional Chinese medicine using liquid chromatography coupled with mass spectrometry. Journal of Chromatography. A 1216: 2045–2062.

    Article  CAS  PubMed  Google Scholar 

  16. Kwon, S.M., S. Kim, N.J. Song, S.H. Chang, Y.J. Hwang, D.K. Yang, J.W. Hong, W.J. Park, and K.W. Park. 2016. Antiadipogenic and proosteogenic effects of luteolin, a major dietary flavone, are mediated by the induction of DnaJ (Hsp40) homolog, subfamily B, member 1. The Journal of Nutritional Biochemistry 30: 24–32.

    Article  CAS  PubMed  Google Scholar 

  17. Seelinger, G., I. Merfort, and C.M. Schempp. 2008. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Medica 74: 1667–1677.

    Article  CAS  PubMed  Google Scholar 

  18. Rauter, A.P., A. Martins, C. Borges, H. Mota-Filipe, R. Pinto, B. Sepodes, and J. Justino. 2010. Antihyperglycaemic and protective effects of flavonoids on streptozotocin-induced diabetic rats. Phytotherapy Research 24: S133–S138.

    Article  PubMed  Google Scholar 

  19. Kapoor, S. 2013. Luteolin and its inhibitory effect on tumor growth in systemic malignancies. Experimental Cell Research 319: 777–778.

    Article  CAS  PubMed  Google Scholar 

  20. Domitrović, R., H. Jakovac, Č. Milin, and B. Radošević-Stašić. 2009. Dose-and time-dependent effects of luteolin on carbon tetrachloride-induced hepatotoxicity in mice. Experimental and Toxicologic Pathology 61: 581–589.

    Article  PubMed  Google Scholar 

  21. Rump, A.F.E., M. Schüssler, D. Acar, A. Cordes, M. Theisohn, R. Rösen, W. Klaus, and U. Fricke. 1994. Functional and antiischemic effects of luteolin-7-glucoside in isolated rabbit hearts. General Pharmacology: The Vascular System 25: 1137–1142.

    Article  CAS  PubMed  Google Scholar 

  22. Qi, L., H. Pan, D. Li, F. Fang, D. Chen, and H. Sun. 2011. Luteolin improves contractile function and attenuates apoptosis following ischemia-reperfusion in adult rat cardiomyocytes. European Journal of Pharmacology 668: 201–207.

    Article  CAS  PubMed  Google Scholar 

  23. Fang, F., D. Li, H. Pan, D. Chen, L. Qi, R. Zhang, and H. Sun. 2011. Luteolin inhibits apoptosis and improves cardiomyocyte contractile function through the PI3K/Akt pathway in simulated ischemia/reperfusion. Pharmacology 88: 149–158.

    Article  CAS  PubMed  Google Scholar 

  24. Kaiserová, H., T. Šimůnek, W.J. Van Der Vijgh, A. Bast, and E. Kvasničková. 2007. Flavonoids as protectors against doxorubicin cardiotoxicity: Role of iron chelation, antioxidant activity and inhibition of carbonyl reductase. Biochimica et Biophysica Acta - Molecular Basis of Disease 1772: 1065–1074.

    Article  Google Scholar 

  25. Han, X., J. Pan, D. Ren, Y. Cheng, P. Fan, and H. Lou. 2008. Naringenin-7-O-glucoside protects against doxorubicin-induced toxicity in H9c2 cardiomyocytes by induction of endogenous antioxidant enzymes. Food and Chemical Toxicology 46: 3140–3146.

    Article  CAS  PubMed  Google Scholar 

  26. Wang, S.Q., X.F. Zhu, X.N. Wang, T. Shen, F. Xiang, and H.X. Lou. 2013. Flavonoids from Malus hupehensis and their cardioprotective effects against doxorubicin-induced toxicity in H9c2 cells. Phytochemistry 87: 119–125.

    Article  CAS  PubMed  Google Scholar 

  27. Wang, G., W. Li, X. Lu, P. Bao, and X. Zhao. 2012. Luteolin ameliorates cardiac failure in type I diabetic cardiomyopathy. Journal of Diabetes Complications 26: 259–265.

    Article  Google Scholar 

  28. Yang, J.T., L.B. Qian, F.J. Zhang, J. Wang, H. Ai, L.H. Tang, and H.P. Wang. 2015. Cardioprotective effects of luteolin on ischemia/reperfusion injury in diabetic rats are modulated by eNOS and the mitochondrial permeability transition pathway. Journal of Cardiovascular Pharmacology 65: 349–356.

    Article  CAS  PubMed  Google Scholar 

  29. Madhesh, M., and M. Vaiyapuri. 2012. Effect of luteolin on lipid peroxidation and antioxidants in acute and chronic periods of isoproterenol induced myocardial infarction in rats. Journal of Acute Medecine 2: 70–76.

    Article  CAS  Google Scholar 

  30. Horder, M., R.C. Elser, W. Gerhardt, M. Mathieu, and E.J. Sampson. 1990. IFCC methods for the measurements of catalytic concentration of enzymes. VII, IFCC method for creatine kinase (ATP: creatine N-phosphotransferase, EC 2.7. 3.2.). IFCC recommendation. Clinica Chimica Acta 190: S4–S17.

    Article  CAS  Google Scholar 

  31. James, J., K.S. Bosch, D.C. Aronson, and J.M. Houtkooper. 1990. Sirius red histophotometry and spectrophotometry of sections in the assessment of the collagen content of liver tissue and its application in growing rat liver. Liver 10: 1–5.

    Article  CAS  PubMed  Google Scholar 

  32. Li, S.Y., X. Yang, A.F. Ceylan-Isik, M. Du, N. Sreejayan, and J. Ren. 2006. Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco (endo) plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch. Diabetologia 49: 1434–1446.

    Article  CAS  PubMed  Google Scholar 

  33. Lee, Y.H., and R.E. Pratley. 2005. The evolving role of inflammation in obesity and the metabolic syndrome. Current Diabetes Reports 5: 70–75.

    Article  CAS  PubMed  Google Scholar 

  34. Engeli, S., R. Negrel, and A.M. Sharma. 2000. Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension 35: 1270–1277.

    Article  CAS  PubMed  Google Scholar 

  35. Panchal, S.K., H. Poudyal, A. Iyer, R. Nazer, A. Alam, V. Diwan, K. Kauter, C. Sernia, F. Campbell, L. Ward, and G. Gobe. 2011. High-carbohydrate, high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats. Journal of Cardiovascular Pharmacology 57: 611–624.

    Article  PubMed  Google Scholar 

  36. Van Harmelen, V., M. Elizalde, P. Ariapart, S. Bergstedt-Lindqvist, S. Reynisdottir, J. Hoffstedt, I. Lundkvist, S. Bringman, and P. Arner. 2000. The association of human adipose angiotensinogen gene expression with abdominal fat distribution in obesity. International Journal of Obesity 24: 673.

  37. Berg, A.H., and P.E. Scherer. 2005. Adipose tissue, inflammation, and cardiovascular disease. Circulation Research 96: 939–949.

    Article  CAS  PubMed  Google Scholar 

  38. Wang, B., and P. Trayhurn. 2006. Acute and prolonged effects of TNF-α on the expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture. Pflügers Archiv 452: 418–427.

    Article  CAS  PubMed  Google Scholar 

  39. Westermann, D., S. Van Linthout, S. Dhayat, N. Dhayat, A. Schmidt, M. Noutsias, X.Y. Song, F. Spillmann, A. Riad, H.P. Schultheiss, and C. Tschöpe. 2007. Tumor necrosis factor-alpha antagonism protects from myocardial inflammation and fibrosis in experimental diabetic cardiomyopathy. Basic Research in Cardiology 102: 500–507.

    Article  CAS  PubMed  Google Scholar 

  40. Mukherjee, S., S.K. Banerjee, M. Maulik, A.K. Dinda, K.K. Talwar, and S.K. Maulik. 2003. Protection against acute adriamycin-induced cardiotoxicity by garlic: Role of endogenous antioxidants and inhibition of TNF-alpha expression. BMC Pharmacology 3: 1–9.

    Article  Google Scholar 

  41. Ueda, H., C. Yamazaki, and M. Yamazaki. 2002. Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biological & Pharmaceutical Bulletin 25: 1197–1202.

    Article  CAS  Google Scholar 

  42. Kim, J.A., D.K. Kim, O.H. Kang, Y.A. Choi, H.J. Park, S.C. Choi, T.H. Kim, K.J. Yun, Y.H. Nah, and Y.M. Lee. 2005. Inhibitory effect of luteolin on TNF-α-induced IL-8 production in human colon epithelial cells. International Immunopharmacology 5: 209–217.

    Article  CAS  PubMed  Google Scholar 

  43. Jia, Z., P. Nallasamy, D. Liu, H. Shah, J.Z. Li, R. Chitrakar, H. Si, J. McCormick, H. Zhu, W. Zhen, and Y. Li. 2015. Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IΚBα/NF-κB signaling pathway. The Journal of Nutritional Biochemistry 26: 293–302.

    Article  CAS  PubMed  Google Scholar 

  44. Woldbaek, P.R., T. Tønnessen, U.L. Henriksen, G. Florholmen, P.K. Lunde, T. Lyberg, and G. Christensen. 2003. Increased cardiac IL-18 mRNA, pro-IL-18 and plasma IL-18 after myocardial infarction in the mouse; a potential role in cardiac dysfunction. Cardiovascular Research 59: 122–131.

    Article  CAS  PubMed  Google Scholar 

  45. Mallat, Z., C. Heymes, A. Corbaz, D. Logeart, S. Alouani, A. Cohen-Solal, T. Seidler, G. Hasenfuss, Y. Chvatchko, A.M. Shah, and A. Tedgui. 2004. Evidence for altered interleukin 18 (IL)-18 pathway in human heart failure. The FASEB Journal 18: 1752–1754.

    CAS  PubMed  Google Scholar 

  46. Srivastava, S., D. Pelloso, H. Feng, L. Voiles, D. Lewis, Z. Haskova, M. Whitacre, S. Trulli, Y.J. Chen, J. Toso, Z.L. Jonak, H.C. Chang, and M.J. Robertson. 2013. Effects of interleukin-18 on natural killer cells: Costimulation of activation through Fc receptors for immunoglobulin. Cancer Immunology, Immunotherapy 62: 1073–1082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Skurk, T., H. Kolb, S. Müller-Scholze, K. Röhrig, H. Hauner, and C. Herder. 2005. The proatherogenic cytokine interleukin-18 is secreted by human adipocytes. European Journal of Endocrinology 152: 863–868.

    Article  CAS  PubMed  Google Scholar 

  48. Xiao, H., H. Li, J.J. Wang, J.S. Zhang, J. Shen, X.B. An, C.C. Zhang, J.M. Wu, Y. Song, X.Y. Wang, and H.Y. Yu. 2017. IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult. European Heart Journal 26: ehx261.

  49. Sagawa, H., A. Naiki-Ito, H. Kato, T. Naiki, Y. Yamashita, S. Suzuki, S. Sato, K. Shiomi, A. Kato, T. Kuno, and Y. Matsuo. 2015. Connexin 32 and luteolin play protective roles in non-alcoholic steatohepatitis development and its related hepatocarcinogenesis in rats. Carcinogenesis 36: 1539–1549.

    CAS  PubMed  Google Scholar 

  50. Dhalla, N.S., R.M. Temsah, and T. Netticadan. 2000. Role of oxidative stress in cardiovascular diseases. Journal of Hypertension 18: 655–673.

    Article  CAS  PubMed  Google Scholar 

  51. Galili, O., D. Versari, K.J. Sattler, M.L. Olson, D. Mannheim, J.P. McConnell, A.R. Chade, L.O. Lerman, and A. Lerman. 2007. Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress. American Journal of Physiology. Heart and Circulatory Physiology 292: H904–H911.

    Article  CAS  PubMed  Google Scholar 

  52. Zhang, Y.C., F.F. Gan, S.B. Shelar, K.Y. Ng, and E.H. Chew. 2013. Antioxidant and Nrf2 inducing activities of luteolin, a flavonoid constituent in Ixeris sonchifolia Hance, provide neuroprotective effects against ischemia-induced cellular injury. Food and Chemical Toxicology 59: 272–280.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

    Nashwa Abu-Elsaad

  2. Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt

    Amr El-Karef

Authors
  1. Nashwa Abu-Elsaad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amr El-Karef
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nashwa Abu-Elsaad.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed were conducted in accordance with the ethical standards of the Scientific Research Ethics Committee, Faculty of Pharmacy in Mansoura University.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abu-Elsaad, N., El-Karef, A. The Falconoid Luteolin Mitigates the Myocardial Inflammatory Response Induced by High-Carbohydrate/High-Fat Diet in Wistar Rats. Inflammation 41, 221–231 (2018). https://doi.org/10.1007/s10753-017-0680-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-017-0680-8

KEY WORDS

Search

Navigation