Polydatin Ameliorates DSS-Induced Colitis in Mice through Inhibition of Nuclear Factor-kappaB Activation

Abstract

Nuclear factor-κB (NF-κB) plays a pivotal role in the regulation of immune and inflammatory responses. The real-time expression level of NF-κB reflects the development of ulcerative colitis (UC). Polydatin has vast pharmacological activities, including inhibiting the production of inflammatory mediators, inducing the production of antioxidants, regulating immune function, etc. The purpose of this study was to investigate the potential inhibitory effects of polydatin on NF-κB pathway activation in a mouse UC model. The results showed that polydatin treatment downregulated NF-κB p65 activity and expression, blocked the expression of TNF-α, IL-6 and IL-1β at both mRNA and protein levels, decreased myeloperoxidase (MPO) activity, and alleviated inflammatory damage of colitis in mice with UC (p < 0.05), suggesting that the anti-inflammation effects of polydatin can be attributed, at least partially, to the blocking of the NF-κB pathway.

Key words

nuclear factor‐κB - polydatin - resveratrol - ulcerative colitis

References

• 1 Sartor R B. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics and prebiotics.  Gastroenterology. 2004;  126 1620-1633
• 2 De Hertogh G, Aerssens J, Geboes K P, Geboes K. Evidence for the involvement of infectious agents in the pathogenesis of Crohn's disease.  World J Gastroenterol. 2008;  14 845-852
• 3 Araki Y, Andoh A, Fujiyama Y. The free radical scavenger edaravone suppresses experimental dextran sulphate sodiuminduced colitis in rats.  Int J Mol Med. 2003;  12 125-129
• 4 Zhang D K, Cheng L N, Huang X L, Shi W, Xiang J Y, Gan H T. Tetrandrine ameliorates dextran-sulfate-sodium-induced colitis in mice through inhibition of nuclear factor -kappaB activation.  Int J Colorectal Dis. 2009;  24 5-12
• 5 Head K, Jurenka J S. Inflammatory bowel disease. Part II: Crohn's disease – pathophysiology and conventional and alternative treatment options.  Altern Med Rev. 2004;  9 360-401
• 6 Karin M. The beginning of the end: IκB kinase and NF-κB activation.  J Biol Chem. 1999;  274 27339-27342
• 7 Yang J, Cui S L, Long Y M. Experimental study on micromolecule polypeptide combining with NEMO-binding domain treating on rats of ulcerative colitis.  J Guangdong Pharm Coll. 2009;  25 180-183
• 8 Ogata H, Hibi T. Cytokine and anti-cytokine therapies for inflammatory bowel disease.  Curr Pharm Des. 2003;  9 1107-1113
• 9 Xie Y N, Wu Z J, Zhao H L. Study on the role of curcumin for treating trinitrobenzenesulphonic acid (TNBS)-induced ulcerative colitis in mice.  Pract J Med Pharm. 2009;  26 46-48
• 10 Ohkusa T, Yoshida T, Sato N, Watanabe S, Tajiri H, Okayasu I. Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion: a possible pathogenic mechanism of ulcerative colitis.  J Med Microbiol. 2009;  58 535-545
• 11 Chen J, Gao M L, Bai X R. Expression of NF-κB and cytokines in human ulcerative colitis and its significance.  World J Gastroenterol. 2009;  17 209-212
• 12 Xu X X, Wang X Y, Tan B, Shen K, Zhong C H, Weng H A, He Z J, Lai F H, Liu L X. Effects of polydatin on inflammatory response in MODS rats.  World J Med Today. 2007;  8 3-5
• 13 Kerem Z, Bilkis I, Flaishman M A, Sivan L. Antioxidant activity and inhibition of alpha-glucosidase by trans-resveratrol, piceid, and a novel trans-stilbene from the roots of Israeli Rumex bucephalophorus L.  J Agric Food Chem. 2006;  54 1243-1247
• 14 Shu S Y, Wang X Y, Ling Z Y, Lu Z Y. Effect of polydatin on phospholipase A2 in lung tissues in rats with endotoxic shock.  Chin J Traumatol. 2004;  7 239-243
• 15 Wang Y X, Kang S H, Zhang Q F, Xu R H. The effect of polydatin on anti-cancer and cancer cell cycle in transplanted swelling mice.  Zhejiang J Integr Trad Chin Western Med. 2003;  13 287-289
• 16 Chen L Y, Han J C, Liang B. Effect of polydatin on expression of p 53 in chronic hypoxic rats.  Shandong Med J. 2006;  46 19-20
• 17 Huang Z S, Wang Z W, Liu M P, Zhong S Q, Li Q M, Rong X L. Protective effects of polydatin against CCl₄-induced injury to primarily cultured rat hepatocytes.  World J Gastroenterol. 1999;  5 41-44
• 18 Du J, Sun L N, Xing W W, Huang B K, Jia M, Wu J Z, Zhang H, Qin L P. Lipid-lowering effects of polydatin from Polygonum cuspidatum in hyperlipidemic hamsters.  Phytomedicine. 2009;  16 652-658
• 19 Singh U P, Singh N P, Singh B, Hofseth L J, Price R L, Nagarkatti M, Nagarkatti P S. Resveratrol (trans-3,5,4′-trihydroxystilbene) induces SIRT1 and down-regulates NF-κB activation to abrogate DSS-induced colitis.  J Pharmacol Exp Ther. ;  DOI: 10.1124/jpet.109.160838 , advance online publication 25 November 2009
  
• 20 Kineman B D, Au A, Paiva N L, Kaiser M S, Brummer E C, Birt D F. Transgenic alfalfa that accumulates piceid (trans-resveratrol 3-O-beta-D-glucopyranoside) requires the presence of beta-glucosidase to inhibit the formation of aberrant crypt foci in the colon of CF-1 mice.  Nutr Cancer. 2007;  58 66-74
• 21 Cooper H S, Murthy S N, Shah R S, Sedergran D J. Clinicopathologic study of dextran sulfate sodium experimental murine colitis.  Lab Invest. 1993;  69 238-249
• 22 Hirata I, Yasumoto S, Toshina K, Inoue T, Nishikawa T, Murano N, Murano M, Wang F Y, Katsu K. Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis.  World J Gastroenterol. 2007;  13 1666-1671
• 23 Renard P, Ernest I, Houbion A, Art M, Le Calvez H, Raes M, Remacle J. Development of a sensitive multi-well colorimetric assay for active NFkappaB.  Nucleic Acids Res. 2001;  29 21
• 24 Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle P A, Schölmerich J, Gross V. Nuclear factor-κB is activated in macrophages and epithelial cells of inflamed intestinal mucosa.  Gastroenterology. 1998;  115 537-569
• 25 Li Z, Zhang D K, Yi W Q, Ou Y Q, Chen Y Q, Gan H T. NF-kappaB p 65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with ulcerative colitis.  Arch Med Res. 2008;  39 729-734
• 26 Gan H T, Ou Y Q, Jia D Q. Activation of nuclear factor-κB and its relationship with cytokine gene expression in colonic mucosa of ulcerative colitis patients.  Chin J Intern Med. 2002;  82 384-388
• 27 Dal Sasso M, Culici M, Guffanti E E, Bianchi T, Fonti E, Braga P C. A combination of budesonide and the SH-metabolite I of erdosteine acts synergistically in reducing chemiluminescence during human neutrophil respiratory burst.  Pharmacology. 2005;  74 127-134
• 28 Zhang J C, Chen K J, Zheng G J. Regulatory effect of Chinese herbal compound for detoxifying and activating blood circulation on expression of NF-kappaB and MMP-9 in aorta of apolipoprotein E gene knocked-out mice.  Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007;  27 40-44
• 29 Hajj Hussein I A, Tohme R, Barada K, Mostafa M H, Freund J N, Jurjus R A, Karam W, Jurjus A. Inflammatory bowel disease in rats: bacterial and chemical interaction.  World J Gastroenterol. 2008;  14 4028-4039
• 30 Camuesco D, Gálvez J, Nieto A, Comalada M, Rodríguez-Cabezas M E, Concha A, Xaus J, Zarzuelo A. Dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, attenuates colonic inflammation in rats with DSS-induced colitis.  J Nutr. 2005;  135 687-694
• 31 Sener G, Aksoy H, Sehirli O, Yüksel M, Aral C, Gedik N, Cetinel S, Yeğen B C. Erdosteine prevents colonic inflammation through its antioxidant and free radical scavenging activities.  Dig Dis Sci. 2007;  52 2122-2132
• 32 Fabris S, Momo F, Ravagnan G, Stevana R. Antioxidant properties of resveratrol and piceid on lipid peroxidation in micelles and monolamellar liposomes.  Biophys Chem. 2008;  135 76-83
• 33 Eaden J A, Abrams K R, Mayberry J F. The risk of colorectal cancer in ulcerative colitis: a meta-analysis.  Gut. 2001;  48 526-535