Protective effects of glycyrrhizic acid by rectal treatment on a TNBS-induced rat colitis model
Ying Liu, Jin Xiang, Min Liu, Shi Wang, Robert J. Lee,
Hong Ding,
Robert J. Lee
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA
Search for more papers by this authorCorresponding Author
Hong Ding
College of Pharmacy, Wuhan University, Wuhan, China
Hong Ding, College of Pharmacy, Wuhan University, Wuhan 430072, China. E-mail: [email protected]Search for more papers by this authorYing Liu, Jin Xiang, Min Liu, Shi Wang, Robert J. Lee,
Hong Ding,
Robert J. Lee
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA
Search for more papers by this authorCorresponding Author
Hong Ding
College of Pharmacy, Wuhan University, Wuhan, China
Hong Ding, College of Pharmacy, Wuhan University, Wuhan 430072, China. E-mail: [email protected]Search for more papers by this authorAbstract
Objectives The research compared rectal and oral treatments with glycyrrhizic acid for trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.
Methods Wistar rats were randomly divided into seven groups: one normal and six with colitis, including TNBS, glycyrrhizic acid (2, 10 and 50 mg/kg, rectally treated and 10 mg/kg, orally treated) and sulfasalazine (positive control, 225 mg/kg rectally treated) groups. Colitis was induced by colonic administration of TNBS in 30% ethanol.
Key findings There were significant pathological changes in colon in TNBS-treated groups, and rectal glycyrrhizic acid significantly attenuated colitis. Myeloperoxidase, tumour necrosis factor-α and interleukin-1β of colon tissue or serum in the rectal glycyrrhizic acid groups were markedly reduced when compared with the TNBS group, and lower than in the orally treated glycyrrhizic acid group. It was further noted that, in vitro, glycyrrhizic acid (up to 100 µg/ml) inhibited interleukin-6 and elevated interleukin-10 production in lipopolysaccharide-activated macrophages, and significantly inhibited proliferation of spleen lymphocytes, suggesting the immunoregulatory function of glycyrrhizic acid.
Conclusions Rectally administered glycyrrhizic acid has significant protective effects against TNBS-induced colitis in rats, and the rectal route may be a complementary treatment for inflammatory bowel disease.
References
- 1 Martin AR et al. The cyclo-oxygenase-2 inhibitor, rofecoxib, attenuates mucosal damage due to colitis induced by trinitrobenzene sulphonic acid in rats. Eur J Pharmacol 2003; 481: 281–291.
- 2 Qin OY et al. Management consensus of inflammatory bowel disease for the Asia-Pacific region. J Gastroenterol Hepatol 2006; 21: 1772–1782.
- 3 Westbrook AM et al. Intestinal mucosal inflammation leads to systemic genotoxicity in mice. Cancer Res 2009; 69: 4827–4834.
- 4 Inoue S et al. Characterization of cytokine expression in the rectal mucosa of ulcerative colitis: correlation with disease activity. Am J Gastroenterol 1999; 94: 2441–2446.
- 5 Katz JA et al. Pathogenesis of inflammatory bowel disease. Curr Opin Gastroenterol 1999; 15: 291–297.
- 6 Ogata H, Hibi T. Cytokine and anti-cytokine therapies for inflammatory bowel disease. Curr Pharm Des 2003; 9: 1107–1113.
- 7 Vermeire S et al. Review article: altering the natural history of Crohn's disease-evidence for and against current therapies. Aliment Pharmacol Ther 2007; 25: 3.
- 8 Yadav VR et al. Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti-inflammatory activity in rat colitis model. AAPS PharmSciTech 2009; 10: 752–762.
- 9 Shanahan F. Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics. Gastroenterology 2001; 120: 622–635.
- 10 Hagar HH et al. Ameliorative effect of pyrrolidinedithiocarbamate on acetic acid-induced colitis in rats. Eur J Pharmacol 2007; 554: 69–77.
- 11 Chung JG et al. Inhibition of N-acetyltransferase activity and DNA-2-aminofluorene adducts by glycyrrhizic acid in human colon tumour cells. Food Chem Toxicol 2000; 38: 163–172.
- 12 Hoever G et al. Antiviral activity of glycyrrhizic acid derivatives against SARS – coronavirus. J Med Chem 2005; 48: 1256–1259.
- 13 Abe K et al. Glycyrrhizin prevents of lipopolysaccharide/d-galactosamine-induced liver injury through down-regulation of matrix metalloproteinase-9 in mice. J Pharm Pharmacol 2008; 60: 91.
- 14 Yuan H et al. Anti-inflammatory effect of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis. World J Gastroenterol 2006; 12: 4578–4581.
- 15 Elliott DE et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol 2003; 284: G385–G391.
- 16 Arita M et al. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci USA 2005; 102: 7671–7676.
- 17 Bouma G et al. Experimental murine colitis is regulated by two genetic loci, including one on chromosome 11 that regulates IL-12 responses. Gastroenterology 2002; 123: 554–565.
- 18 Lee S et al. 2′, 4′, 6′-Tris (methoxymethoxy) chalcone protects against trinitrobenzene sulfonic acid-induced colitis and blocks tumor necrosis factor- -induced intestinal epithelial inflammation via heme oxygenase 1-dependent and independent pathways. Biochem Pharmacol 2007; 74: 870–880.
- 19 Chevalier E et al. Beneficial effect of trimebutine and N-monodesmethyl trimebutine on trinitrobenzene sulfonic acid-induced colitis in rats. Life Sci 2004; 76: 319–329.
- 20 Lowry O et al. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–275.
- 21 Misra H, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247: 3170–3175.
- 22 Ohkawa H et al. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351–358.
- 23 Mahgoub AA et al. Evaluating the prophylactic potential of zafirlukast against the toxic effects of acetic acid on the rat colon. Toxicol Lett 2003; 145: 79–87.
- 24 Jagtap AG et al. Effect of polyherbal formulation on experimental models of inflammatory bowel diseases. J Ethnopharmacol 2004; 90: 195–204.
- 25 Ha CL et al. Immunomodulatory effect of Glossogyne tenuifolia in murine peritoneal macrophages and splenocytes. J Ethnopharmacol 2006; 107: 116–125.
- 26 Hansen MB et al. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 1989; 119: 203–210.
- 27 Zimecki M et al. Bacteriophages provide regulatory signals in mitogen-induced murine splenocyte proliferation. Cell Mol Biol Lett 2003; 8: 699–712.
- 28 Appleyard CB, Wallace JL. Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugs. Am J Physiol 1995; 269: G119–G11G.
- 29 Martin AR et al. Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. Biochem Pharmacol 2004; 67: 1399–1410.
- 30 Gearry RB et al. High incidence of Crohn's disease in Canterbury, New Zealand: results of an epidemiologic study. Inflamm Bowel Dis 2006; 12: 936–943.
- 31 Davidson N et al. T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. J Exp Med 1996; 184: 241–251.
- 32 Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis 2000; 6: 21–33.
- 33 Burich A et al. Helicobacter-induced inflammatory bowel disease in IL-10-and T cell-deficient mice. Am J Physiol Gastrointest Liver Physiol 2001; 281: G764–G778.
- 34 Liu BG et al. Altered protein profile of lymphocytes in an antigen-specific model of colitis: a comparative proteomic study. Inflamm Res 2007; 56: 377–384.
- 35 Boyle NT, Connor TJ. MDMA (‘Ecstasy’) suppresses innate IFN-gamma production and signalling, and inhibits MHC II expression on APCs. Eur Neuropsychopharmacol 2006; 16(Suppl. 1): 25–26.
- 36 Feng C et al. 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: 1292–1298.
- 37 Neurath MF. Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question. Trends Immunol 2001; 22: 225–225.
- 38 Chen KY et al. Activation of nuclear factor-kappa B and effects of pyrrolidine ithiocarbamate on TNBS-induced rat colitis. World J Gastroenterol 2005; 11: 1508–1514.
- 39 Bossone C et al. Alterations in spontaneous contractions in vitro after repeated inflammation of rat distal colon. Am J Physiol Gastrointest Liver Physiol 2001; 280: G949–G957.
- 40 Arulampalam V, Pettersson S. Uncoupling the p38 MAPK kinase in IBD: a double edged sword? Gut 2002; 50: 446–447.
- 41 Siegmund B. Interleukin-1 beta converting enzyme (caspase-1) in intestinal inflammation. Biochem Pharmacol 2002; 64: 1–8.
- 42 Maihofner C et al. Expression of cyclooxygenase-2 parallels expression of interleukin-1beta, interleukin-6 and NF-kappaB in human colorectal cancer. Carcinogenesis 2003; 24: 665–671.
- 43 Duque J et al. Up-regulation of cyclooxygenase-2 by interleukin-1 beta in colon carcinoma cells. Cell Signal 2006; 18: 1262–1269.
- 44 Travis S et al. RDP58 is a novel and potentially effective oral therapy for ulcerative colitis. Inflamm Bowel Dis 2005; 11: 713–719.
- 45 Størmer F et al. Glycyrrhizic acid in liquorice – evaluation of health hazard. Food Chem Toxicol 1993; 31: 303–312.
- 46 Saito T et al. An autopsy case of licorice-induced hypokalemic rhabdomyolysis associated with acute renal failure: special reference to profound calcium deposition in skeletal and cardiac muscle. Nippon Jinzo Gakkai Shi 1994; 36: 1308–1314.
- 47 Gomez-Sanchez E, Gomez-Sanchez C. Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. Am J Physiol Endocrinol Metab 2006; 263: E1125.
