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Glycyrrhizin Improves Fatty Liver Symptoms, Increases Adiponectin and Reduces UCP2 Expression in Wistar Rats

  • Hamedeh Bagheri
  • Parichehreh YaghmaeiEmail author
  • Mohamadhosein Modaresi
  • Marjan Sabbaghian
  • Azadeh Ebrahim-HabibiEmail author
Article
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Abstract

Glycyrrhizin (GL) is the main bioactive component in the extract of licorice root, with beneficial effects on metabolic syndrome. This study investigates the effect of GL on biochemical and histological parameters and UCP2 gene expression in a rodent nonalcoholic steatosis model. Thirty-two male Wistar rats were classified into four groups randomly: control (normal diet with standard rat chow), high-cholesterol diet (HCD for 12 weeks) and two experimental groups (HCD for 12 weeks then shifted to normal diet plus receiving either 20 mg/kg or 100 mg/kg of glycyrrhizin for 4 weeks). At the end of experiment, in the HCD group, body weight, glucose and insulin levels were increased, lipid profile was impaired, and the markers related to liver were abnormal, while adiponectin, catalase and superoxide dismutase levels were decreased. Histological analysis of liver sections showed the appearance of hepatic fibrosis and steatosis, and UCP2 gene expression was increased significantly. GL treatment at both doses and especially at 100 mg/kg ameliorated the situation, and levels of UCP2 were decreased significantly. In conclusion, administration of glycyrrhizin can improve liver fibrosis through down-regulating the UCP2 expression.

Keywords

Glycyrrhizin UCP2 NAFLD Cholesterol 

Notes

Acknowledgements

This study has been performed in the laboratory complex of Science and Research Branch of Azad University, Tehran.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interests to publish this manuscript.

References

  1. 1.
    Kotronen A, Yki-Järvinen H (2008) Fatty liver. Arterioscler Thromb Vasc Biol 28(1):27–38CrossRefPubMedGoogle Scholar
  2. 2.
    Oosterveer MH, Van Dijk TH, Tietge UJ, Boer T, Havinga R, Stellaard F, Groen AK, Kuipers F, Reijngoud D-J (2009) High fat feeding induces hepatic fatty acid elongation in mice. PLoS ONE 4(6):e6066CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Hübscher S (2006) Histological assessment of non-alcoholic fatty liver disease. Histopathology 49(5):450–465CrossRefPubMedGoogle Scholar
  4. 4.
    Wu X, Zhang L, Gurley E, Studer E, Shang J, Wang T, Wang C, Yan M, Jiang Z, Hylemon PB (2008) Prevention of free fatty acid–induced hepatic lipotoxicity by 18β-glycyrrhetinic acid through lysosomal and mitochondrial pathways. Hepatology 47(6):1905–1915CrossRefPubMedGoogle Scholar
  5. 5.
    Sacco R, Pucci L, Sivozhelezov V, Pellegrini L, Giacomelli L, Longo V (2015) Prevention of vascular damage with Lisosan G wheat extract: the in vitro basis for a clinical investigation. Eur Rev Med Pharmacol Sci 19(8):1517–1519PubMedGoogle Scholar
  6. 6.
    Fernando HA, Chandramouli C, Rosli D, Lam YL, Yong ST, Yaw HP, Ton SH, Kadir KA, Sainsbury A (2014) Glycyrrhizic acid can attenuate metabolic deviations caused by a high-sucrose diet without causing water retention in male Sprague-Dawley rats. Nutrients 6(11):4856–4871CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    El-Magd NFA, El-Karef A, El-Shishtawy MM, Eissa LA (2015) Hepatoprotective effects of glycyrrhizin and omega-3 fatty acids on Nuclear Factor-kappa B pathway in thioacetamide-induced fibrosis in rats. Egypt J Basic Appl Sci 2(2):65–74CrossRefGoogle Scholar
  8. 8.
    Pecqueur C, Alves-Guerra M-C, Gelly C, Lévi-Meyrueis C, Couplan E, Collins S, Ricquier D, Bouillaud F, Miroux B (2001) Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation. J Biol Chem 276(12):8705–8712CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Echtay KS, Murphy MP, Smith RA, Talbot DA, Brand MD (2002) Superoxide activates mitochondrial uncoupling protein 2 from the matrix side Studies using targeted antioxidants. J Biol Chem 277(49):47129–47135CrossRefPubMedGoogle Scholar
  10. 10.
    Brand MD, Esteves TC (2005) Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3. Cell Metab 2(2):85–93CrossRefPubMedGoogle Scholar
  11. 11.
    O’Connor E (2019) The role of mitochondrial uncoupling protein 3 in T cell function. Doctoral dissertation, The University of DublinGoogle Scholar
  12. 12.
    Fülöp P, Derdák Z, Sheets A, Sabo E, Berthiaume EP, Resnick MB, Wands JR, Paragh G, Baffy G (2006) Lack of UCP2 reduces fas-mediated liver injury in ob/ob mice and reveals importance of cell-specific UCP2 expression. Hepatology 44(3):592–601CrossRefPubMedGoogle Scholar
  13. 13.
    Dludla PV, Nkambule BB, Tiano L, Louw J, Jastroch M, Mazibuko-Mbeje SE (2018) Uncoupling proteins as a therapeutic target to protect the diabetic heart. Pharmacol Res 137:11–24CrossRefPubMedGoogle Scholar
  14. 14.
    Heinitz S, Piaggi P, Yang S, Bonfiglio S, Steel J, Krakoff J, Votruba SB (2018) Response of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction. Int J Obes 42(5):974–984CrossRefGoogle Scholar
  15. 15.
    Hu Y-W, Zhang P, Yang J-Y, Huang J-L, Ma X, Li S-F, Zhao J-Y, Hu Y-R, Wang Y-C, Gao J-J (2014) Nur77 decreases atherosclerosis progression in apoE–/– mice fed a high-fat/high-cholesterol diet. PLoS ONE 9(1):e87313CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Karkhaneh L, Yaghmaei P, Parivar K, Sadeghizadeh M, Ebrahim-Habibi A (2016) Effect of trans-chalcone on atheroma plaque formation, liver fibrosis and adiponectin gene expression in cholesterol-fed NMRI mice. Pharmacol Rep 68(4):720–727CrossRefPubMedGoogle Scholar
  17. 17.
    Singh S, Bigoniya P, Shrivastava B, Sharma J (2016) Hypo-glycemic profile of gymnemic acid and glycyrrhizic acid on high fructose diet related obesity induced diabetes. Int J Med Pharm Sci (IJMPS) 6(3):61–84Google Scholar
  18. 18.
    Najafian M, Ebrahim-Habibi A, Yaghmaei P, Parivar K, Larijani B (2010) Core structure of flavonoids precursor as an antihyperglycemic and antihyperlipidemic agent: an in vivo study in rats. Acta Biochim Pol 57(4):553CrossRefPubMedGoogle Scholar
  19. 19.
    Najafian M, Ebrahim-Habibi A, Hezareh N, Yaghmaei P, Parivar K, Larijani B (2011) Trans-chalcone: a novel small molecule inhibitor of mammalian alpha-amylase. Mol Biol Rep 38(3):1617–1620CrossRefPubMedGoogle Scholar
  20. 20.
    Sil R, Ray D, Chakraborti AS (2013) Glycyrrhizin ameliorates insulin resistance, hyperglycemia, dyslipidemia and oxidative stress in fructose-induced metabolic syndrome-X in rat model. Indian J Exp Biol 51(2):129–138PubMedGoogle Scholar
  21. 21.
    Yazdanparast R, Bahramikia S, Ardestani A (2008) Nasturtium officinale reduces oxidative stress and enhances antioxidant capacity in hypercholesterolaemic rats. Chem Biol Interact 172(3):176–184CrossRefPubMedGoogle Scholar
  22. 22.
    Chung AP, Gurtu S, Chakravarthi S, Moorthy M, Palanisamy UD (2018) Geraniin protects high-fat diet-induced oxidative stress in Sprague Dawley rats. Front Nutr 5:17CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Cheng HS, Yaw HP, Ton SH, Choy SM, Kong JMXF, Kadir KA (2016) Glycyrrhizic acid prevents high calorie diet–induced metabolic aberrations despite the suppression of peroxisome proliferator-activated receptor γ expression. Nutrition 32(9):995–1001CrossRefPubMedGoogle Scholar
  24. 24.
    Chavin KD, Yang S, Lin HZ, Chatham J, Chacko VP, Hoek JB, Walajtys-Rode E, Rashid A, Chen C-H, Huang C-C (1999) Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J Biol Chem 274(9):5692–5700CrossRefPubMedGoogle Scholar
  25. 25.
    Horimoto M, Fülöp P, Derdák Z, Wands JR, Baffy G (2004) Uncoupling protein-2 deficiency promotes oxidant stress and delays liver regeneration in mice. Hepatology 39(2):386–392CrossRefPubMedGoogle Scholar
  26. 26.
    Ajith TA (2018) Role of mitochondria and mitochondria-targeted agents in non-alcoholic fatty liver disease. Clin Exp Pharmacol Physiol 45(5):413–421CrossRefPubMedGoogle Scholar
  27. 27.
    Nazari S, Rameshrad M, Hosseinzadeh H (2017) Toxicological effects of Glycyrrhiza glabra (Licorice): a review. Phytother Res 31:1635–1650CrossRefPubMedGoogle Scholar

Copyright information

© The National Academy of Sciences, India 2019

Authors and Affiliations

  1. 1.Department of Biology, Science and Research BranchIslamic Azad UniversityTehranIran
  2. 2.Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran
  3. 3.Department of Andrology, Reproductive Biomedicine Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran
  4. 4.Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences InstituteTehran University of Medical SciencesTehranIran
  5. 5.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran

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