, Volume 41, Issue 4, pp 1276–1289 | Cite as

Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice

  • Bárbara B. Colombo
  • Victor Fattori
  • Carla F. S. Guazelli
  • Tiago H. Zaninelli
  • Thacyana T. Carvalho
  • Camila R. Ferraz
  • Allan J. C. Bussmann
  • Kenji W. Ruiz-Miyazawa
  • Marcela M. Baracat
  • Rúbia Casagrande
  • Waldiceu A. VerriJr


The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn’s disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.


inflammatory bowel syndrome inflammation inflammatory pain oxidative stress abdominal pain 



Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Central Multiusuária de Laboratórios de Pesquisa da UEL (CMLP), Fundação Araucária, and Paraná State Government.

Compliance with Ethical Standards

The proceedings of care and handling of the mice were carried out in accordance with the directions of the International Association for the Study of the Pain (IASP) and approved by the Londrina State University Ethics Committee on Animal Research and Welfare (process number: 3307.2015.37).

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    de Souza, H.S.P., and C. Fiocchi. 2015. Immunopathogenesis of IBD : Nature Publishing Group 13:13–27.
  2. 2.
    Molodecky, Natalie A., Ing Shian Soon, Doreen M. Rabi, William A. Ghali, Mollie Ferris, Greg Chernoff, Eric I. Benchimol, et al. 2012. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142. Elsevier Inc: 46–54. Scholar
  3. 3.
    Burisch, Johan, Tine Jess, Matteo Martinato, and Peter L. Lakatos. 2013. The burden of inflammatory bowel disease in Europe. Journal of Crohn's & Colitis 7. European Crohn’s and Colitis Organisation: 322–337. Scholar
  4. 4.
    Soon, Ing Shian, Natalie A. Molodecky, Doreen M. Rabi, William A. Ghali, Herman W. Barkema, and Gilaad G. Kaplan. 2012. The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis. BMC Gastroenterology 12: 51. Scholar
  5. 5.
    Abegunde, Ayokunle T., Bashir H. Muhammad, and Tauseef Ali. 2016. Preventive health measures in inflammatory bowel disease. World Journal of Gastroenterology 22. Baishideng Publishing Group Inc: 7625–7644. Scholar
  6. 6.
    Neurath, Markus F. 2014. Cytokines in inflammatory bowel disease. Nature Reviews Immunology 14. Nature Publishing Group: 329–342. Scholar
  7. 7.
    Baumgart, Daniel C., and William J. Sandborn. 2007. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 369: 1641–1657. Scholar
  8. 8.
    de Lange, Katrina M., and Jeffrey C. Barrett. 2015. Understanding inflammatory bowel disease via immunogenetics. Journal of Autoimmunity 64: 91–100. Scholar
  9. 9.
    Molodecky, Natalie A., and Gilaad G. Kaplan. 2010. Environmental risk factors for inflammatory bowel disease. Gastroenterology & Hepatology 6: 339–346. Scholar
  10. 10.
    Atreya, Raja, Michael Zimmer, Brigitte Bartsch, Maximilian J. Waldner, Imke Atreya, Helmut Neumann, Kai Hildner, et al. 2011. Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14 + macrophages. Gastroenterology 141. Elsevier Inc: 2026–2038. Scholar
  11. 11.
    Beltrán, Caroll J., Lucía E. Núñez, David Díaz-Jiménez, Nancy Farfan, Enzo Candia, Claudio Heine, Francisco López, María Julieta González, Rodrigo Quera, and Marcela A. Hermoso. 2010. Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflammatory Bowel Diseases 16: 1097–1107. Scholar
  12. 12.
    McAlindon, M.E., C.J. Hawkey, and Y.R. Mahida. 1998. Expression of interleukin 1 beta and interleukin 1 beta converting enzyme by intestinal macrophages in health and inflammatory bowel disease. Gut 42: 214–219.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lee, Cheng Hiang, Peter Hsu, Brigitte Nanan, Ralph Nanan, Melanie Wong, Kevin J. Gaskin, Rupert W. Leong, Ryan Murchie, Aleixo M. Muise, and Michael O. Stormon. 2014. Novel de novo mutations of the interleukin-10 receptor gene lead to infantile onset inflammatory bowel disease. Journal of Crohn's & Colitis 8. European Crohn’s and Colitis Organisation: 1551–1556. Scholar
  14. 14.
    Karp, Sean M., and Timothy R. Koch. 2006. Oxidative Stress and Antioxidants in Inflammatory Bowel Disease. Disease-a-Month 52: 199–207. Scholar
  15. 15.
    Pavlick, K.P., F.S. Laroux, J. Fuseler, R.E. Wolf, L. Gray, J. Hoffman, and M.B. Grisham. 2002. Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radical Biology and Medicine 33: 311–322.CrossRefPubMedGoogle Scholar
  16. 16.
    Lorincz, C., K. Szasz, and L. Kisfaludy. 1976. The synthesis of ethyl apovincaminate. Arzneimittel-Forschung 26: 1907.PubMedGoogle Scholar
  17. 17.
    Bereczki, D., and I. Fekete. 1999. Asystematic review of vinpocetine therapy in acute ischaemic stroke. European Journal of Clinical Pharmacology 55: 349–352.CrossRefPubMedGoogle Scholar
  18. 18.
    Horvath, Beata, Zsolt Marton, Robert Halmosi, Tamas Alexy, Laszlo Szapary, Judit Vekasi, Zsolt Biro, Tamas Habon, Gabor Kesmarky, and Kalman Toth. 2002. In Vitro Antioxidant Properties of Pentoxifylline, Piracetam, and Vinpocetine. Clinical Neuropharmacology 25: 37–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Ruiz-Miyazawa, Kenji W., Felipe A. Pinho-Ribeiro, Ana C. Zarpelon, Larissa Staurengo-Ferrari, Rangel L. Silva, Jose C. Alves-Filho, Thiago M. Cunha, Fernando Q. Cunha, Rubia Casagrande, and Waldiceu A. Verri. 2015. Vinpocetine reduces lipopolysaccharide-induced inflammatory pain and neutrophil recruitment in mice by targeting oxidative stress, cytokines and NF-κB. Chemico-Biological Interactions 237. Elsevier Ireland Ltd: 9–17. Scholar
  20. 20.
    Ruiz-Miyazawa, Kenji W., Ana C. Zarpelon, Felipe A. Pinho-Ribeiro, Gabriela F. Pavão-De-Souza, Rubia Casagrande, and Waldiceu A. Verri. 2015. Vinpocetine reduces carrageenan-induced inflammatory hyperalgesia in mice by inhibiting oxidative stress, cytokine production and NF-κB activation in the paw and spinal cord. PLoS One 10: 1–18. Scholar
  21. 21.
    Fattori, Victor, Sergio M. Borghi, Carla F.S. Guazelli, Andressa C. Giroldo, Jefferson Crespigio, Allan J.C. Bussmann, Letícia Coelho-Silva, et al. 2017. Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-κB activation in mice. Pharmacological Research 120. Elsevier Ltd: 10–22. Scholar
  22. 22.
    Abdel-Salam, Omar M.E. 2006. Vinpocetine and piracetam exert antinociceptive effect in visceral pain model in mice. Pharmacological Reports 58: 680–691.PubMedGoogle Scholar
  23. 23.
    Jeon, Kye-Im, Xiangbin Xu, Toru Aizawa, Jae Hyang Lim, Hirofumi Jono, Dong-Seok Kwon, Jun-Ichi Abe, Bradford C. Berk, Jian-Dong Li, and Chen Yan. 2010. Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proceedings of the National Academy of Sciences of the United States of America 107: 9795–9800. Scholar
  24. 24.
    Guazelli, Carla F.S., Victor Fattori, Barbara B. Colombo, Sandra R. Georgetti, Fabiana T.M.C. Vicentini, Rubia Casagrande, Marcela M. Baracat, and Waldiceu A. Verri Jr. 2013. Quercetin-Loaded Microcapsules Ameliorate Experimental Colitis in Mice by Anti-inflammatory and Antioxidant Mechanisms. Journal of Natural Products 76: 200–208.CrossRefPubMedGoogle Scholar
  25. 25.
    Polgár, M., L. Vereczkey, and I. Nyáry. 1985. Pharmacokinetics of vinpocetine and its metabolite, apovincaminic acid, in plasma and cerebrospinal fluid after intravenous infusion. Journal of Pharmaceutical and Biomedical Analysis 3: 131–139.CrossRefPubMedGoogle Scholar
  26. 26.
    Lee, Ji Yun, Hyo Sook Kang, Byoung Eon Park, Hyo Jin Moon, Sang Soo Sim, and Chang Jong Kim. 2009. Inhibitory effects of Geijigajakyak-Tang on trinitrobenzene sulfonic acid-induced colitis. Journal of Ethnopharmacology 126: 244–251. Scholar
  27. 27.
    Barbosa, Andre Luiz Dos Reis. 2011. Colite experimental induzida pelo ácido trinitrobenzeno sulfônico (TNBS) em ratos reduz a resposta hipernociceptiva inflamatória- papel das vias endocanabinóides, opióides endógenos e NO/GMPC/PKG/K+ATP. Universidade Federal do Ceará.Google Scholar
  28. 28.
    Pereira, L.M.S., R.C.P. Lima-Júnior, A.X.C. Bem, C.G. Teixeira, L.S. Grassi, R.P. Medeiros, R.D. Marques-Neto, R.B. Callado, K.S. Aragão, D.V.T. Wong, M.L. Vale, G.A.C. Brito, and R.A. Ribeiro. 2013. Blockade of TRPA1 with HC-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system. European Journal of Pain (United Kingdom) 17: 223–233. Scholar
  29. 29.
    Laird, J.M.A., L. Martinez-Caro, E. Garcia-Nicas, and F. Cervero. 2001. A new model of visceral pain and referred hyperalgesia in the mouse. Pain 92: 335–342. Scholar
  30. 30.
    Bernstein, Charles N., Michael Fried, J.H. Krabshuis, Henry Cohen, R. Eliakim, Suleiman Fedail, Richard Gearry, et al. 2010. World gastroenterology organization practice guidelines for the diagnosis and management of IBD in 2010. Inflammatory Bowel Diseases 16: 112–124. Scholar
  31. 31.
    Kane, S.V. 2006. Systematic review: Adherence issues in the treatment of ulcerative colitis. Alimentary Pharmacology and Therapeutics 23: 577–585. Scholar
  32. 32.
    Goldberg, Rimma, and Peter M. Irving. 2015. Toxicity and response to thiopurines in patients with inflammatory bowel disease. Expert Review of Gastroenterology & Hepatology 9: 1–10. Scholar
  33. 33.
    Hansen, Richard A., Gerald Gartlehner, Gregory E. Powell, and Robert S. Sandler. 2007. Serious Adverse Events With Infliximab: Analysis of Spontaneously Reported Adverse Events. Clinical Gastroenterology and Hepatology 5: 729–735. Scholar
  34. 34.
    Higgins, Peter D.R., Martha Skup, Parvez M. Mulani, Jay Lin, and Jingdong Chao. 2015. Increased Risk of Venous Thromboembolic Events With Corticosteroid vs Biologic Therapy for Inflammatory Bowel Disease. Clinical Gastroenterology and Hepatology 13. Elsevier, Inc: 316–321. Scholar
  35. 35.
    Lukert, B.P., and L.G. Raisz. 1990. Glucocorticoid-induced osteoporosis: pathogenesis and management. Annals of Internal Medicine 112: 352–364. Scholar
  36. 36.
    Balestreri, R., L. Fontana, and F. Astengo. 1987. A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. Journal of the American Geriatrics Society 35: 425–430.CrossRefPubMedGoogle Scholar
  37. 37.
    Thal, L.J., D.P. Salmon, B. Lasker, D. Bower, and M.R. Klauber. 1989. The safety and lack of efficacy of vinpocetine in Alzheimer’s disease. Journal of the American Geriatrics Society 37: 515–520.CrossRefPubMedGoogle Scholar
  38. 38.
    Zhang, Weiwei, Yining Huang, Ying Li, Liming Tan, Jianfei Nao, Hongtao Hu, Jingyu Zhang, Chen Li, Yuenan Kong, and Yulin Song. 2016. Efficacy and Safety of Vinpocetine as Part of Treatment for Acute Cerebral Infarction: A Randomized, Open-Label, Controlled, Multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) Trial. Clinical Drug Investigation 36. Springer International Publishing: 697–704. Scholar
  39. 39.
    Zhuang, Jianhui, Wenhui Peng, Hailing Li, Yuyan Lu, Ke Wang, Fan Fan, Shuang Li, and Yawei Xu. 2013. Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-kB dependent mechanisms in apoE−/− mice. PLoS One 8: 1–12. Scholar
  40. 40.
    Higa, A., T. Eto, and Y. Nawa. 1997. Evaluation of the role of neutrophils in the pathogenesis of acetic acid-induced colitis in mice. Scandinavian Journal of Gastroenterology 32: 564–568.CrossRefPubMedGoogle Scholar
  41. 41.
    Blake, K.M., S.O. Carrigan, A.C. Issekutz, and A.W. Stadnyk. 2004. Neutrophils migrate across intestinal epithelium using β2 integrin (CD11b/CD18)-independent mechanisms. Clinical and Experimental Immunology 136: 262–268. Scholar
  42. 42.
    Carrigan, Svetlana O., Amy L. Weppler, Andrew C. Issekutz, and Andrew W. Stadnyk. 2005. Neutrophil differentiated HL-60 cells model Mac-1 (CD11b/CD18)-independent neutrophil transepithelial migration. Immunology 115: 108–117. Scholar
  43. 43.
    Naito, Yuji, Tomohisa Takagi, and Toshikazu Yoshikawa. 2007. Molecular fingerprints of neutrophil-dependent oxidative stress in inflammatory bowel disease. Journal of Gastroenterology 42: 787–798. Scholar
  44. 44.
    Klebanoff, Seymour J. 2005. Myeloperoxidase: friend and foe. Journal of Leukocyte Biology 77: 598–625. Scholar
  45. 45.
    Krawisz, J.E., P. Sharon, and W.F. Stenson. 1984. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology 87: 1344–1350.PubMedGoogle Scholar
  46. 46.
    Pravda, Jay. 2005. Radical induction theory of ulcerative colitis. World Journal of Gastroenterology 11: 2371–2384.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Achitei, D., A. Ciobica, G. Balan, E. Gologan, C. Stanciu, and G. Stefanescu. 2013. Different profile of peripheral antioxidant enzymes and lipid peroxidation in active and non-active inflammatory bowel disease patients. Digestive Diseases and Sciences 58: 1244–1249. Scholar
  48. 48.
    Pereira, Cristiana, Rosa Coelho, Daniela Grácio, Cláudia Dias, Marco Silva, Armando Peixoto, Pedro Lopes, Carla Costa, João Paulo Teixeira, Guilherme Macedo, and Fernando Magro. 2016. DNA Damage and Oxidative DNA Damage in InflammatoryBowel Disease. Journal of Crohn's & Colitis 10: 1316–1323. Scholar
  49. 49.
    Pacher, Pál, Joseph S. Beckman, and Lucas Liaudet. 2007. Nitric oxide and peroxynitrite in health and disease. Physiological Reviews 87: 315–424. Scholar
  50. 50.
    Chiurchiu, V., and M. Maccarrone. 2011. Chronic inflammatory disorders and their redox control: from molecular mechanisms to therapeutic opportunities. Antioxidants & Redox Signaling 15: 2605–2641. Scholar
  51. 51.
    Christman, John W., and Timothy S. Blackwell. 2000. Redox Regulation of Nuclear Factor Kappa B: Therapeutic Potential for Attenuating Inflammatory Responses. Critical Care 162: 153–162.Google Scholar
  52. 52.
    Maloy, Kevin J., and Fiona Powrie. 2011. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474: 298–306. Scholar
  53. 53.
    Amrouche-Mekkioui, Ilhem, and Bahia Djerdjouri. 2012. N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice. European Journal of Pharmacology 691. Elsevier: 209–217. Scholar
  54. 54.
    Zaki, Hala Fahmy, and Rania Mohsen Abdelsalam. 2013. Vinpocetine protects against liver ischemia-reperfusion injury. Canadian Journal of Physiology and Pharmacology 91: 1064–1070. Scholar
  55. 55.
    Santos, M.S., A.I. Duarte, P.I. Moreira, and C.R. Oliveira. 2000. Synaptosomal response to oxidative stress: effect of vinpocetine. Free Radical Research 32: 57–66.CrossRefPubMedGoogle Scholar
  56. 56.
    Aghazadeh, Rahim, Mohammad Reza Zali, Ali Bahari, Kamyar Amin, Farzin Ghahghaie, and Farzad Firouzi. 2005. Inflammatory bowel disease in Iran: A review of 457 cases. Journal of Gastroenterology and Hepatology (Australia) 20: 1691–1695. Scholar
  57. 57.
    Wagtmans, M.J., H.W. Verspaget, C.B.H.W. Lamers, and R.A. van Hogezand. 1998. Crohn’s Disease in the Elderly: A Comparison With Young Adults. Journal of Clinical Gastroenterology 27: 129–133.CrossRefPubMedGoogle Scholar
  58. 58.
    Regueiro, Miguel, Julia B. Greer, and Eva Szigethy. 2017. Etiology and Treatment of Pain and Psychosocial Issues in Patients with Inflammatory Bowel Diseases. Gastroenterology 152. Elsevier Ltd: 430–439. Scholar
  59. 59.
    Binshtok, A.M., H. Wang, and K. Zimmermann. 2008. Nociceptors Are Interleukin-1ßSensors. J Neurosci 28: 14062–14073. Nociceptors.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Jin, X. 2006. Acute p38-Mediated Modulation of Tetrodotoxin-Resistant Sodium Channels in Mouse Sensory Neurons by Tumor Necrosis Factor-α. Journal of Neuroscience 26: 246–255. Scholar
  61. 61.
    Wright, A. 1999. Recent concepts in the neurophysiology of pain. Manual Therapy 4: 196–202. Scholar
  62. 62.
    Zarpelon, A.C., T.M. Cunha, J.C. Alves-Filho, L.G. Pinto, S.H. Ferreira, D. Xu I B McInnes, F.Y. Liew, F.Q. Cunha, and W.A. Verri. 2013. IL-33/ST2 signalling contributes to carrageenin-induced innate inflammation and inflammatory pain: Role of cytokines, endothelin-1 and prostaglandin E2. British Journal of Pharmacology 169: 90–101. Scholar
  63. 63.
    Yamacita-Borin, Fabiane Y., Ana C. Zarpelon, Felipe A. Pinho-Ribeiro, Victor Fattori, Jose C. Alves-Filho, Fernando Q. Cunha, Thiago M. Cunha, Rubia Casagrande, and Waldiceu A. Verri. 2015. Superoxide anion-induced pain and inflammation depends on TNFα/TNFR1 signaling in mice. Neuroscience Letters 605. Elsevier Ireland Ltd: 53–58. Scholar
  64. 64.
    Magro, D.A.C., M.S.N. Hohmann, S.S. Mizokami, T.M. Cunha, J.C. Alves-Filho, R. Casagrande, S.H. Ferreira, F.Y. Liew, F.Q. Cunha, and A. Verri Jr. 2013. An interleukin-33/ST2 signaling deficiency reduces overt pain-like behaviors in mice. Brazilian Journal of Medical and Biological Research 46: 601–606. Scholar
  65. 65.
    Ma, Fei, Liping Zhang, and Karin N. Westlund. 2009. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons. Molecular Pain 5: 31. Scholar
  66. 66.
    Salvemini, Daniela, Joshua W. Little, Timothy Doyle, and William L. Neumann. 2011. Roles of reactive oxygen and nitrogen species in pain. Free Radical Biology & Medicine 51: 951–966. Scholar
  67. 67.
    Wang, Zq, Frank Porreca, and Salvatore Cuzzocrea. 2004. A newly identified role for superoxide in inflammatory pain. The Journal of Pharmacology and Experimental Therapeutics 309: 869–878. Scholar
  68. 68.
    Maioli, N.A., A.C. Zarpelon, S.S. Mizokami, C. Calixto-Campos, C.F.S. Guazelli, M.S.N. Hohmann, F.A. Pinho-Ribeiro, T.T. Carvalho, M.F. Manchope, C.R. Ferraz, R. Casagrande, and W.A. Verri Jr. 2015. The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2. Brazilian Journal of Medical and Biological Research 48: 321–331. Scholar
  69. 69.
    Zhou, Xiaoping, X.W. Dong, and James Crona. 2003. Vinpocetine is a potent blocker of rat NaV1. 8 tetrodotoxin-resistant sodium channels. Journal of Pharmacology and Experimental Therapeutics 306: 498–504. Scholar
  70. 70.
    Knyihar-Csillik, Elizabeth, Laszlo Vecsei, Andras Mihaly, Robert Fenyo, Ibolya Farkas, Beata Krisztin-Peva, and Bertalan Csillik. 2007. Effect of vinpocetine on retrograde axoplasmic transport. Annals of Anatomy 189: 39–45. Scholar
  71. 71.
    Akbar, A., Y. Yiangou, P. Facer, J.R.F. Walters, P. Anand, and S. Ghosh. 2008. Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain. Gut 57: 923–929. Scholar
  72. 72.
    Ludwiczek, O., E. Vannier, I. Borggraefe, A. Kaser, B. Siegmund, C.A. Dinarello, and Herbert Tilg. 2004. Imbalance between interleukin-1 agonists and antagonists: Relationship to severity of inflammatory bowel disease. Clinical and Experimental Immunology 138: 323–329. Scholar
  73. 73.
    Steidler, L., W. Hans, L. Schotte, S. Neirynck, F. Obermeier, W. Falk, W. Fiers, and E. Remaut. 2000. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289: 1352–1355.CrossRefPubMedGoogle Scholar
  74. 74.
    Li, Zhi, De Kui Zhang, Wen Quan Yi, Qin Ouyang, You Qin Chen, and Hua Tian Gan. 2008. NF-KB p65 Antisense Oligonucleotides May Serve as a Novel Molecular Approach for the Treatment of Patients with Ulcerative Colitis. Archives of Medical Research 39. Elsevier Inc: 729–734. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Departamento de Ciências Patológicas, Centro de Ciências BiológicasUniversidade Estadual de LondrinaLondrinaBrazil
  2. 2.Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Hospital UniversitárioUniversidade Estadual de LondrinaLondrinaBrazil

Personalised recommendations