Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice

  • Taya, Sirinya (Department of Molecular Pathology, Osaka City University Graduate School of Medicine) ;
  • Kakehashi, Anna (Department of Molecular Pathology, Osaka City University Graduate School of Medicine) ;
  • Wongpoomchai, Rawiwan (Department of Biochemistry, Faculty of Medicine, Chiang Mai University) ;
  • Gi, Min (Department of Molecular Pathology, Osaka City University Graduate School of Medicine) ;
  • Ishii, Naomi (Department of Molecular Pathology, Osaka City University Graduate School of Medicine) ;
  • Wanibuchi, Hideki (Department of Molecular Pathology, Osaka City University Graduate School of Medicine)
  • Published : 2016.06.01


Ulcerative colitis (UC) results from colonic epithelial barrier defects and impaired mucosal immune responses. In this study, we aimed to investigate the modifying effects of a Spirogyra neglecta extract (SNE), a polysaccharide extract (PE) and a chloroform fraction (CF) on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the mechanisms. To induce colitis, ICR mice received 3% DSS in their drinking water for 7 days. Seven days preceding the DSS treatment, oral administration of SNE, PE and CF at doses of 50, 25 and 0.25 mg/kg body weight (low dose), 200, 100 and 1 mg/kg body weight (high dose) and vehicle was started and continued for 14 days. Histologic findings showed that DSS-induced damage of colonic epithelial structure and inflammation was attenuated in mice pre-treated with SNE, PE and CF. Furthermore, SNE and PE significantly protected colonic epithelial cells from DSS-induced cell cycle arrest, while SNE, PE and CF significantly diminished apoptosis. Proteome analysis demonstrated that SNE and PE might ameliorate DSS-induced colitis by inducing antioxidant enzymes, restoring impaired mitochondria function, and regulating inflammatory cytokines, proliferation and apoptosis. These results suggest that SNE and PE could prevent DSS-induced colitis in ICR mice by protection against and/or aiding recovery from damage to the colonic epithelium, reducing ROS and maintaining normal mitochondrial function and apoptosis.


Supported by : Japanese Association of University Women (JAUW)


  1. Araki Y, Mukaisyo K, Sugihara H, et al (2010). Increased apoptosis and decreased proliferation of colonic epithelium in dextran sulfate sodium-induced colitis in mice. Oncol Rep, 24, 869-74.
  2. Ardizzone S, Bianchi Porro G (2005). Biologic therapy for inflammatory bowel disease. Drugs, 65, 2253-86.
  3. Balkwill F (2006). TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev, 25, 409-16.
  4. Baribault H, Penner J, Iozzo RV, et al (1994). Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice. Genes Dev, 8, 2964-73.
  5. Baumgart DC, Sandborn WJ (2007). Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet, 369, 1641-57.
  6. Chattopadhyay N, Ghosh T, Sinha S, et al (2010). Polysaccharides from Turbinaria conoides: Structural features and antioxidant capacity. Food Chemistry, 118, 823-9.
  7. Chen Y, Ferguson SS, Negishi M, et al (2004). Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor. J Pharmacol Exp Ther, 308, 495-501.
  8. Cho EJ, Shin JS, Noh YS, et al (2011). Anti-inflammatory effects of methanol extract of Patrinia scabiosaefolia in mice with ulcerative colitis. J Ethnopharmacol, 136, 428-35.
  9. Chu EC, Chai J, Ahluwalia A, et al (2007). Mesalazine downregulates c-Myc in human colon cancer cells. A key to its chemopreventive action? Aliment Pharmacol Ther, 25, 1443-9.
  10. Cooper HS, Murthy SN, Shah RS, et al (1993). Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest, 69, 238-49.
  11. Coulombe PA, Omary MB (2002). ‘Hard' and ‘soft' principles defining the structure, function and regulation of keratin intermediate filaments. Curr Opin Cell Biol, 14, 110-22.
  12. Damiani CR, Benetton CA, Stoffel C, et al (2007). Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodium. J Gastroenterol Hepatol, 22, 1846-51.
  13. De Robertis M, Massi E, Poeta ML, et al (2011). The AOM/DSS murine model for the study of colon carcinogenesis: From pathways to diagnosis and therapy studies. J Carcinog, 10, 9.
  14. Ding Y, Lu B, Chen D, et al (2010). Proteomic analysis of colonic mucosa in a rat model of irritable bowel syndrome. Proteomics, 10, 2620-30.
  15. Gluckmann M, Fella K, Waidelich D, et al (2007). Prevalidation of potential protein biomarkers in toxicology using iTRAQ reagent technology. Proteomics, 7, 1564-74.
  16. Habtezion A, Toivola DM, Butcher EC, et al (2005). Keratin- 8-deficient mice develop chronic spontaneous Th2 colitis amenable to antibiotic treatment. J Cell Sci, 118, 1971-80.
  17. Hans W, Scholmerich J, Gross V, et al (2000). The role of the resident intestinal flora in acute and chronic dextran sulfate sodium-induced colitis in mice. Eur J Gastroenterol Hepatol, 12, 267-73.
  18. Hendrickson BA, Gokhale R, Cho JH (2002). Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev, 15, 79-94.
  19. Hsieh SY, Shih TC, Yeh CY, et al (2006). Comparative proteomic studies on the pathogenesis of human ulcerative colitis. Proteomics, 6, 5322-31.
  20. Itzkowitz SH, Yio X (2004). Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol, 287, 7-17.
  21. Iwamoto M, Koji T, Makiyama K, et al (1996). Apoptosis of crypt epithelial cells in ulcerative colitis. J Pathol, 180, 152-9.<152::AID-PATH649>3.0.CO;2-Y
  22. Kaser A, Zeissig S, Blumberg RS (2010). Inflammatory bowel disease. Annu Rev Immunol, 28, 573-621.
  23. Kitajima S, Takuma S, Morimoto M (2000). Histological analysis of murine colitis induced by dextran sulfate sodium of different molecular weights. Experimental Animals, 49, 9-15.
  24. Kwon KH, Murakami A, Tanaka T, et al (2005). Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of pro-inflammatory gene expression. Biochemical Pharmacol, 69, 395-406.
  25. Lee HJ, Lee HG, Choi KS, et al (2013). Diallyl trisulfide suppresses dextran sodium sulfate-induced mouse colitis: NF-kappaB and STAT3 as potential targets. Biochem Biophys Res Commun, 437, 267-73.
  26. Lin JJ, Warren KS, Wamboldt DD, et al (1997). Tropomyosin isoforms in nonmuscle cells. Int Rev Cytol, 170, 1-38.
  27. Martinez-Augustin O, Merlos M, Zarzuelo A, et al (2008). Disturbances in metabolic, transport and structural genes in experimental colonic inflammation in the rat: a longitudinal genomic analysis. BMC Genomics, 9, 490.
  28. Medhi B, Prakash A, Avti PK, et al (2008). Effect of Manuka honey and sulfasalazine in combination to promote antioxidant defense system in experimentally induced ulcerative colitis model in rats. Indian J Exp Biol, 46, 583-90.
  29. Ngo DH, Kim SK (2013). Sulfated polysaccharides as bioactive agents from marine algae. Int J Biol Macromol, 62, 70-5.
  30. Nishikawa M, Oshitani N, Matsumoto T, et al (2005). Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis. Br J Cancer, 93, 331-7.
  31. Ontawong A, Saowakon N, Vivithanaporn P, et al (2013). Antioxidant and renoprotective effects of Spirogyra neglecta (Hassall) Kutzing extract in experimental type 2 diabetic rats. Biomed Res Int, 2013, 820786.
  32. Owens DW, Wilson NJ, Hill AJ, et al (2004). Human keratin 8 mutations that disturb filament assembly observed in inflammatory bowel disease patients. J Cell Sci, 117, 1989-99.
  33. Paradossi G, Cavalieri F, Pizzoferrato L, et al (1999). A physico-chemical study on the polysaccharide ulvan from hot water extraction of the macroalga Ulva. Int J Biological Macromolecules, 25, 309-15.
  34. Ponzielli R, Katz S, Barsyte-Lovejoy D, et al (2005). Cancer therapeutics: targeting the dark side of Myc. Eur J Cancer, 41, 2485-501.
  35. Rana SV, Sharma S, Prasad KK, et al (2014). Role of oxidative stress & antioxidant defence in ulcerative colitis patients from north India. Indian J Med Res, 139, 568-71.
  36. Riezzo I, Turillazzi E, Bello S, et al (2014). Chronic nandrolone administration promotes oxidative stress, induction of proinflammatory cytokine and TNF-alpha mediated apoptosis in the kidneys of CD1 treated mice. Toxicol Appl Pharmacol, 280, 97-106.
  37. Rubin DC, Shaker A, Levin MS (2012). Chronic intestinal inflammation: inflammatory bowel disease and colitisassociated colon cancer. Front Immunol, 3, 107.
  38. Shao P, Chen X, Sun P (2014). Chemical characterization, antioxidant and antitumor activity of sulfated polysaccharide from Sargassum horneri. Carbohydr Polym, 105, 260-9.
  39. Sifroni KG, Damiani CR, Stoffel C, et al (2010). Mitochondrial respiratory chain in the colonic mucosal of patients with ulcerative colitis. Mol Cell Biochem, 342, 111-5.
  40. Song X, Bandow J, Sherman J, et al (2008). iTRAQ experimental design for plasma biomarker discovery. J Proteome Res, 7, 2952-8.
  41. Sturgill MG, Lambert GH (1997). Xenobiotic-induced hepatotoxicity: mechanisms of liver injury and methods of monitoring hepatic function. Clin Chem, 43, 1512-26.
  42. Terzic J, Grivennikov S, Karin E, et al (2010). Inflammation and colon cancer. Gastroenterol, 138, 2101-14.
  43. Tessner TG, Cohn SM, Schloemann S, et al (1998). Prostaglandins prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice. Gastroenterol, 115, 874-82.
  44. Thumvijit T, Taya S, Punvittayagul C, et al (2014). Cancer chemopreventive effect of Spirogyra neglecta (Hassall) Kutzing on diethylnitrosamine-induced hepatocarcinogenesis in rats. Asian Pac J Cancer Prev, 15, 1611-6.
  45. Thumvijit T, Thuschana W, Amornlerdpison D, et al (2013). Evaluation of hepatic antioxidant capacities of Spirogyra neglecta (Hassall) Kutzing in rats. Interdiscip Toxicol, 6, 152-6.
  46. Treton X, Pedruzzi E, Cazals-Hatem D, et al (2011). Altered endoplasmic reticulum stress affects translation in inactive colon tissue from patients with ulcerative colitis. Gastroenterol, 141, 1024-35.
  47. Wijesekara I, Pangestuti R, Kim SK (2011). Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae. Carbohydrate Polymers, 84, 14-21.
  48. Wirtz S, Neufert C, Weigmann B, et al (2007). Chemically induced mouse models of intestinal inflammation. Nat Protoc, 2, 541-6.
  49. Yousef M, Pichyangkura R, Soodvilai S, et al (2012). Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: Therapeutic efficacy and possible mechanisms of action. Pharmacological Res, 66, 66-79.
  50. Zhao L, Wu H, Zhao A, et al (2014). The in vivo and in vitro study of polysaccharides from a two-herb formula on ulcerative colitis and potential mechanism of action. J Ethnopharmacol, 153, 151-9.