Amal Ragab, Nasr Nasr, Khalid Kahilo


Glycyrrhizc acid (GA) is one of the herbal plants with a proved hepato-protective effect. The current study was carried out to estimate the hepato-protective effect of GA against liver fibrosis and to disclose its mode of action. Thirty two male albino rats were randomly distributed into 4 groups (n=8), i.e., control group, GA group, CCl4 group and CCl4 + GA group. Liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), liver histopathology, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CT) and gene expression of integrin subunit β like 1 (ITGBL1) were analyzed. The obtained data revealed that GA remarkably protected CCl4-induced liver injury as reflected by reduced AST, ALT, GGT, and fibrosis compared with the CCl4-only group. Moreover, GA significantly reduced the levels of MDA, as well as increased the activity of SOD and CT. Consequently, GA prevents CCl4-induced fibrosis in rats. The prophylactic action of GA against liver fibrosis was mediated through its antioxidant and anti-inflammatory activities. Additionally, GA downregulated fibrogenic ITGBL1.

Key words: glycyrrhizc acid; ITGBL1; liver fibrosis; integrins

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Anthony P P, Ishak K G, Nayak N C, Poulsen H E, Scheuer P J, Sobin L H. The morphology of cirrhosis. Recommendations on definition, nomenclature, and classification by a working group sponsored by the World Health Organization, J Clin Pathol 1978; 31(5): 395–414.

Buti M, Fung S, Gane E, Afdhal N H, Flisiak R, Gurel S, Flaherty J F, Martins E B, Yee L J, Dinh P, Bornstein J D, Mani Subramanian G, Janssen H L, George J, Marcellin P. Long-term clinical outcomes in cirrhotic chronic hepatitis B patients treated with tenofovir disoproxil fumarate for up to 5 years, Hepatol Int 2015; 9(2): 243–50.

Blachier M, Leleu H, Peck-Radosavljevic M, Valla D C, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data, J Hepatol 2013; 58(3): 593–608.

Disease G B D, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016, Lancet 2017; 390(10100): 1211–59.

Heidelbaugh J J, Bruderly M. Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation, Am Fam Physician 2006; 74(5): 756-62.

Hernandez-Gea V, Friedman S L. Pathogenesis of liver fibrosis, Annu Rev Pathol 2011; 6: 425–56.

Pellicoro A, Ramachandran P, Iredale J P, Fallowfield J A. Liver fibrosis and repair: immune regulation of wound healing in a solid organ, Nat Rev Immunol 2014; 14(3): 181–94.

Luo B H, Springer T A. Integrin structures and conformational signaling, Curr Opin Cell Biol 2006; 18(5): 579–86.

Conroy K P, Kitto L J, Henderson N C. alphav integrins: key regulators of tissue fibrosis, Cell Tissue Res 2016; 365(3): 511–9.

Patsenker E, Popov Y, Stickel F, Jonczyk A, Goodman S L, Schuppan D. Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression, Gastroenterology 2008; 135(2): 660–70.

Wang M, Gong Q, Zhang J, Chen L, Zhang Z, Lu L, Yu D, Han Y, Zhang D, Chen P, Zhang X, Yuan Z, Huang J, Zhang X. Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis, Sci Rep 2017; 7: 43446.

Elgazar A A, Selim N M, Abdel-Hamid N M, El-Magd M A, El Hefnawy H M. Isolates from Alpinia officinarum Hance attenuate LPS induced inflammation in HepG2: Evidence from In Silico and In Vitro Studies, Phytotherapy Research 2018; 32(7): 1273–88.

Del Prete A, Scalera A, Iadevaia M D, Miranda A, Zulli C, Gaeta L, Tuccillo C, Federico A, Loguercio C. Herbal products: benefits, limits, and applications in chronic liver disease, Evid Based Complement Alternat Med 2012; 2012: 837939.

Hanje A J, Fortune B, Song M, Hill D, McClain C. The use of selected nutrition supplements and complementary and alternative medicine in liver disease, Nutr Clin Pract 2006; 21(3): 255–72.

Feng C, Wang H, Yao C, Zhang J, Tian Z. Diammonium glycyrrhizinate, a component of traditional Chinese medicine Gan-Cao, prevents murine T-cell-mediated fulminant hepatitis in IL-10- and IL-6-dependent manners, Int Immunopharmacol 2007; 7(10): 1292–8.

van Rossum T G, Vulto A G, de Man R A, Brouwer J T, Schalm S W. Review article: glycyrrhizin as a potential treatment for chronic hepatitis C, Aliment Pharmacol Ther 1998; 12(3): 199–205.

Constandinou C, Henderson N, Iredale J P. Modeling liver fibrosis in rodents, Methods Mol Med 2005; 117: 237–50.

Alzahrani F A, El-Magd M A, Abdelfattah-Hassan A, Saleh A A, Saadeldin I M, El-Shetry E S, Badawy A A, Alkarim S. Potential Effect of Exosomes Derived from Cancer Stem Cells and MSCs on Progression of DEN-Induced HCC in Rats, Stem Cells International 2018; 2018: 17

El-Bayomi K M, Saleh A A, Awad A, El-Tarabany M S, El-Qaliouby H S, Afifi M, El-Komy S, Essawi W M, Almadaly E A, El-Magd M A. Association of CYP19A1 gene polymorphisms with anoestrus in water buffaloes, Reproduction, Fertility and Development 2018; 30(3): 487–497.

Abd-Allah S H, Shalaby S M, Abd-Elbary E, Saleh A A, El-Magd M A. Human peripheral blood CD34+ cells attenuate oleic acid-induced acute lung injury in rats, Cytotherapy 2015; 17(4): 443–53.

Bancroft J D, Stevens A, Turner D R, Theory and practice of histological techniques, Fourth Edition ed., Churchill Livingstone, New York, 1996.

Chatterjee R, Mitra A. An overview of effective therapies and recent advances in biomarkers for chronic liver diseases and associated liver cancer, Int Immunopharmacol 2015; 24(2): 335–345.

Paquet K J, Kamphausen U. The carbon-tetrachloride-hepatotoxicity as a model of liver damage. First report: Long-time biochemical changes, Acta Hepatogastroenterol (Stuttg) 1975; 22(2): 84–8.

Li X X, Zheng Q C, Wang Y, Zhang H X. Theoretical insights into the reductive metabolism of CCl4 by cytochrome P450 enzymes and the CCl4-dependent suicidal inactivation of P450, Dalton Trans 2014; 43(39): 14833–40.

Chen P J, Huang C, Meng X M, Li J. Epigenetic modifications by histone deacetylases: Biological implications and therapeutic potential in liver fibrosis, Biochimie 2015; 116: 61–9.

Santos J C, Valentim I B, de Araujo O R, Ataide Tda R, Goulart M O. Development of nonalcoholic hepatopathy: contributions of oxidative stress and advanced glycation end products, Int J Mol Sci 2013; 14(10): 19846–66.

Elpek G O. Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update, World J Gastroenterol 2014; 20(23): 7260–76.

Reeves H L, Friedman S L. Activation of hepatic stellate cells--a key issue in liver fibrosis, Front Biosci 2002; 7: d808–26.

Friedman S L. Mechanisms of hepatic fibrogenesis, Gastroenterology 2008; 134(6): 1655–69.

Wan X Y, Luo M, Li X D, He P. Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine, Chem Biol Interact 2009; 181(1): 15–9.

Rahman S, Sultana S. Chemopreventive activity of glycyrrhizin on lead acetate mediated hepatic oxidative stress and its hyperproliferative activity in Wistar rats, Chem Biol Interact 2006; 160(1): 61–9.

Tu C T, Li J, Wang F P, Li L, Wang J Y, Jiang W. Glycyrrhizin regulates CD4+T cell response during liver fibrogenesis via JNK, ERK and PI3K/AKT pathway, Int Immuno-pharmacol 2012; 14(4): 410–21.



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