Skip to main content

Advertisement

Log in

Effect of trans-chalcone on atheroma plaque formation, liver fibrosis and adiponectin gene expression in cholesterol-fed NMRI mice

  • Original Research Article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Trans-chalcone is the precursor molecule to flavonoids and possesses antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of trans-chalcone on atheroma plaque formation and the relevant biochemical parameters in high cholesterol diet (HCD)-fed NMRI mice.

Methods

Fifty male NMRI mice were divided into 5 groups (n = 10 per group): control (received a normal diet); HCD (received an additional 2% cholesterol for 18 weeks); sham (received a HCD for 12 weeks and were then shifted to a normal diet and trans-chalcone vehicle (sunflower oil) for 6 weeks), and two experimental groups (received a HCD for 12 weeks and were then shifted to a normal diet and either 12 mg/kg or 24 mg/kg trans-chalcone for 6 weeks).

Results

After 12 weeks, HCD-induced atheroma plaques were observed by hematoxylin and eosin staining of aortic sections. At the end of experiment, the following factors had significantly increased in the HCD group: body weight, insulin resistance, and serum levels of triglycerides, total-cholesterol, glucose, insulin, leptin, liver enzymes (AST and ALT), malondialdehyde and direct bilirubin. The serum levels of high-density lipoprotein cholesterol, adiponectin, superoxide dismutase, and glutathione had considerably decreased. Histologic analysis of liver sections indicated hepatic fibrosis and steatosis. Treatment by both doses of trans-chalcone, particularly the 24 mg/kg dose, significantly attenuated these alterations.

Conclusions

Administration of trans-chalcone improved the consequences of atheroma plaque formation and liver fibrosis via increased expression of adiponectin, generation of higher levels of antioxidant enzymes, as well as modulation of serum leptin and lipid profiles.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Tanaka K, Nakanishi T. Obesity as a risk factor for various diseases: necessity of lifestyle changes for healthy aging. Appl Hum Sci 1996;15(4):139–48.

    Article  CAS  Google Scholar 

  2. Gremese E, Tolusso B, Gigante MR, Ferraccioli G. Obesity as a risk and severity factor in rheumatic diseases (autoimmune chronic inflammatory diseases). Front Immunol 2014;11(5):576.

    Google Scholar 

  3. Garg S, Maurer H, Reed K, Selagamsetty R. Diabetes and cancer: two diseases with obesity as a common risk factor. Diabetes Obes Metab 2014;16(2):97–110.

    Article  CAS  PubMed  Google Scholar 

  4. Davoodi SH, Malek-Shahabi T, Malekshahi-Moghadam A, Shahbazi R, Esmaeili S. Obesity as an important risk factor for certain types of cancer. Iran J Cancer Prev 2013;6(4):186.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, et al. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update consensus panel guide to comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases. Circulation 2002;106(3):388–91.

    Article  PubMed  Google Scholar 

  6. Park D, Kyung J, Kim D, Hwang SY, Choi EK, Kim YB. Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light therapy in rabbits fed a high-cholesterol diet. Lab Anim Res 2012;28(1):39–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lohmann C, Schafer N, von Lukowicz T, Sokrates Stein MA, Boren J, Rutti S, et al. Atherosclerotic mice exhibit systemic inflammation in periadventitial and visceral adipose tissue, liver, and pancreatic islets. Atherosclerosis 2009; 207(2):360–7.

    Article  CAS  PubMed  Google Scholar 

  8. Mohammadi M, Alipour M, Alipour M, Vatankhah A. Effects of high cholesterol diet and parallel chronic exercise on erythrocyte primary antioxidant enzymes and plasma total antioxidant capacity in Dutch rabbits. Int J Endocrinol Metab 2006;4(1):30–40.

    CAS  Google Scholar 

  9. Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 2008;93(11_supplement_1):s64–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Aprahamian TR, Sam F. Adiponectin in cardiovascular inflammation and obesity. Int J Inflamm 2011;2011:376909.

    Article  CAS  Google Scholar 

  11. Saravanan G, Ponmurugan P, Deepa MA, Senthilkumar B. Anti-obesity action of gingerol: effect on lipid profile, insulin, leptin, amylase and lipase in male obese rats induced by a high-fat diet. J Sci Food Agric 2014;94(14):2972–7.

    Article  CAS  PubMed  Google Scholar 

  12. Sung YY, Kim DS, Choi G, Kim SH, Kim HK. Dohaekseunggi-tang extract inhibits obesity, hyperlipidemia, and hypertension in high-fat diet-induced obese mice. BMC Complement Altern Med 2014;14:372.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Grassi D, Desideri G, Ferri C. Flavonoids: antioxidants against atherosclerosis. Nutrients 2010;2(8):889–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. de Kok TM, de Waard P, Wilms LC, van Breda SG. Antioxidative and antigenotoxic properties of vegetables and dietary phytochemicals: the value of genomics biomarkers in molecular epidemiology. Mol Nutr Food Res 2010;54(2):208–17.

    Article  PubMed  CAS  Google Scholar 

  15. Grassi D, Desideri G, Croce G, Tiberti S, Aggio A, Ferri C. Flavonoids, vascular function and cardiovascular protection. CurrPharm Des 2009;15(10):1072–84.

    CAS  Google Scholar 

  16. Mirmiran P, Bahadoran Z, Moslehi N, Bastan S, Azizi F. Colors of fruits and vegetables and 3-year changes of cardiometabolic risk factors in adults: Tehran lipid and glucose study. Eur J Clin Nutr 2015;69(11):1215–9.

    Article  CAS  PubMed  Google Scholar 

  17. Rahman MA. Chalcone: A valuable insight into the recent advances and potential pharmacological activities. Chem Sci J 2011;29:1–16.

    Google Scholar 

  18. van Dam RM, Naidoo N, Landberg R. Dietary flavonoids and the development of type 2 diabetes and cardiovascular diseases: review of recent findings. Curr Opin Lipidol 2013;24(1):25–33.

    Article  PubMed  CAS  Google Scholar 

  19. Zhang EH, Wang RF, Guo SZ, Liu B. An update on antitumor activity of naturally occurring chalcones. Evid Based Complement Altern Med 2013;2013:815621.

    Google Scholar 

  20. Heldt H-W, Heldt F. Pflanzenbiochemie. Springer; 1996.

  21. Palleros DR. Solvent-free synthesis of chalcones. J Chem Educ 2004;81(9): 1345.

    Article  CAS  Google Scholar 

  22. Najafian M, Ebrahim-Habibi A, Yaghmaei P, Parivar K, Larijani B. Core structure of flavonoids precursor as an antihyperglycemic and antihyperlipidemic agent: an in vivo study in rats. Acta Biochim Pol 2010;57(4):553.

    Article  CAS  PubMed  Google Scholar 

  23. Najafian M, Ebrahim-Habibi A, Hezareh N, Yaghmaei P, Parivar K, Larijani B. Trans-chalcone: a novel small molecule inhibitor of mammalian alpha-amylase. Mol Biol Rep 2011;38(3):1617–20.

    Article  CAS  PubMed  Google Scholar 

  24. Sikander M, Malik S, Yadav D, Biswas S, Katare DP, Jain SK. Cytoprotective activity of a trans-chalcone against hydrogen peroxide induced toxicity in hepatocellular carcinoma (HepG2) cells. Asian Pac J Cancer Prev 2011; 12(10):2513–6.

    PubMed  Google Scholar 

  25. Yadav VR, Prasad S, Sung B, Aggarwal BB. The role of chalcones in suppression of NF-kappaB-mediated inflammation and cancer. Int Immunopharmacol 2011;11(3):295–309.

    Article  CAS  PubMed  Google Scholar 

  26. Lamoke F, Labazi M, Montemari A, Parisi G, Varano M, Bartoli M. Transchalcone prevents VEGF expression and retinal neovascularization in the ischemic retina. Exp Eye Res 2011;93(4):350–4.

    Article  CAS  PubMed  Google Scholar 

  27. Hu Y-W, Zhang P, Yang J-Y, Huang J-L, Ma X, Li S-F, et al. Nur77 Decreases atherosclerosis progression in apoE-/- mice fed a high-fat/high-cholesterol diet. PLOS ONE 2014;9(1).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Barnea M, Shamay A, Stark AH, Madar Z. A high-fat diet has a tissue-specific effect on adiponectin and related enzyme expression. Obesity 2006;14(12): 2145–53.

    Article  CAS  PubMed  Google Scholar 

  29. Xu YJ, Zhang M, Ji L, Elimban V, Chen L, Dhalla NS. Suppression of high lipid diet induced by atherosclerosis sarpogrelate. J Cell Mol Med 2012;16(10): 2394–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Blokhina O, Virolainen E, Fagerstedt KV. Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot 2003;91:179–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Stanton MC, Chen SC, Jackson JV, Rojas-Triana A, Kinsley D, Cui L, et al. Inflammatory Signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice. J Inflamm (Lond) 2011;16(8):8.

    Article  CAS  Google Scholar 

  32. Hall P, Cash J. What is the real function of the liver ‘function’ tests? Ulst Med J 2012;81(1):30–6.

    Google Scholar 

  33. Noeman SA, Hamooda HE, Baalash AA. Biochemical study of oxidative stress markers in the liver, kidney and heart of high fat diet induced obesity in rats. Diabetol Metab Syndr 2011;3(1):17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Demori I, Voci A, Fugassa E, Burlando B. Combined effects of high-fat diet and ethanol induce oxidative stress in rat liver. Alcohol 2006;40(3):185–91.

    Article  CAS  PubMed  Google Scholar 

  35. Srinivasan K, Patole PS, Kaul CL, Ramarao P. Reversal of glucose intolerance by pioglitazone in high fat diet-fed rats. Methods Find Exp Clin Pharmacol 2004;26(5):327–33.

    Article  CAS  PubMed  Google Scholar 

  36. Yao J, Zhi M, Minhu C. Effect of silybin on high-fat-induced fatty liver in rats. Braz J Med Biol Res 2011;44(7):652–9.

    CAS  PubMed  Google Scholar 

  37. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005;26(3):439–51.

    Article  CAS  PubMed  Google Scholar 

  38. Robinson K, Prins J, Venkatesh B. Clinical review: adiponectin biology and its role in inflammation and critical illness. Crit Care 2011;15(2):221.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME. Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun 2004;316(3):924–9.

    Article  CAS  PubMed  Google Scholar 

  40. Ma K, Cabrero A, Saha PK, Kojima H, Li L, Chang BH-J, et al. Increased betaoxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J Biol Chem 2002;277(38):34658–61.

    Article  CAS  PubMed  Google Scholar 

  41. Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002;35(2): 373–9.

    Article  CAS  PubMed  Google Scholar 

  42. Ghantous CM, Azrak Z, Hanache S, Abou-Kheir W, Zeidan A. Differential role of leptin and adiponectin in cardiovascular system. Int J Endocrinol 2015; 534320.

  43. Singh RB, Mengi SA, Xu YJ, Arneja AS, Dhalla NS. Pathogenesis of atherosclerosis: a multifactorial process. Exp Clin Cardiol 2002;7(1):40–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Wung B, Ni C, Wang D. ICAM-1 induction by TNF-alpha and 1L-6 is mediated by distinct pathways via Rac in endothelial cells. J Biomed Sci 2005;12(1): 91–101.

    Article  CAS  PubMed  Google Scholar 

  45. Shen KH, Chang JK, Hsu YL, Kuo PL. Chalcone arrests cell cycle progression and induces apoptosis through induction ofmitochondrial pathwayand inhibition of nuclear factor kappa B signalling in human bladder cancer cells. Basic Clin Pharmacol Toxicol 2007;101(4):254–61.

    Article  CAS  PubMed  Google Scholar 

  46. Liu Y-C, Hsieh C-W, Wu C-C, Wung B-S. Chalcone inhibits the activation of NF-κB and STAT3 in endothelial cells via endogenous electrophile. Life Sci 2007;80(15):1420–30.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Parichehreh Yaghmaei or Azadeh Ebrahim-Habibi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karkhaneh, L., Yaghmaei, P., Parivar, K. et al. Effect of trans-chalcone on atheroma plaque formation, liver fibrosis and adiponectin gene expression in cholesterol-fed NMRI mice. Pharmacol. Rep 68, 720–727 (2016). https://doi.org/10.1016/j.pharep.2016.03.004

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2016.03.004

Keywords

Navigation