Digestive Diseases and Sciences

, Volume 57, Issue 1, pp 99–108 | Cite as

A Tannic Acid-Based Medical Food, Cesinex®, Exhibits Broad-Spectrum Antidiarrheal Properties: A Mechanistic and Clinical Study

  • Aixia Ren
  • Weiqiang Zhang
  • Hugh Greg Thomas
  • Amy Barish
  • Stephen Berry
  • Jeffrey S. Kiel
  • Anjaparavanda P. Naren
Original Article



The purpose of this investigation was to evaluate the efficacy and tolerability of a tannic acid-based medical food, Cesinex®, in the treatment of diarrhea and to investigate the mechanisms underlying its antidiarrheal effect.


Cesinex® was prescribed to six children and four adults with diarrhea. Patient records were retrospectively reviewed for the primary outcome. Cesinex® and its major component, tannic acid, were tested for their effects on cholera toxin-induced intestinal fluid secretion in mice. Polarized human gut epithelial cells (HT29-CL19A cells) were used to investigate the effects of tannic acid on epithelial barrier properties, transepithelial chloride secretion, and cell viability.


Successful resolution of diarrheal symptoms was reported in nine of ten patients receiving Cesinex®. The treatment of HT29-CL19A cells with clinically relevant concentrations of tannic acid (0.01–1 mg/ml) significantly increased transepithelial resistance (TER) and inhibited the cystic fibrosis transmembrane conductance regulator (CFTR)-dependent or the calcium-activated Cl secretion. Tannic acid could also improve the impaired epithelial barrier function induced by tumor necrosis factor alpha (TNFα) and inhibited the disrupting effect of TNFα on the epithelial barrier function in these cells. Cholera toxin (CTX)-induced mouse intestinal fluid secretion was significantly reduced by the administration of Cesinex® or tannic acid. Cesinex® has high antioxidant capacity.


Cesinex® demonstrates efficacy and a good safety profile in the treatment of diarrhea. The broad-spectrum antidiarrheal effect of Cesinex® can be attributed to a combination of factors: its ability to improve the epithelial barrier properties, to inhibit intestinal fluid secretion, and the high antioxidant capacity.


Diarrhea Cesinex® Tannic acid Intestinal barrier Intestinal fluid secretion Chloride channels 





Bowel movement


Calcium-activated chloride channel


Cystic fibrosis transmembrane conductance regulator


Cholera toxin




Niflumic acid


Tannic acid


Trolox® equivalent antioxidant capacity


Transepithelial resistance


Tumor necrosis factor alpha



This work is supported by the US National Institutes of Health (NIH) (DK074996 and DK080834 to A.P.N.). Hall Bioscience partially funded the mechanistic studies (for purchasing the reagents and materials needed for the experiments).


  1. 1.
    Yan F, Polk DB. Probiotics as functional food in the treatment of diarrhea. Curr Opin Clin Nutr Metab Care. 2006;9:717–721.PubMedCrossRefGoogle Scholar
  2. 2.
    Thielman NM, Guerrant RL. Clinical practice. Acute infectious diarrhea. N Engl J Med. 2004;350:38–47.PubMedCrossRefGoogle Scholar
  3. 3.
    Esteban Carretero J, Durbán Reguera F, López-Argüeta Alvarez S, López Montes J. A comparative analysis of response to vs. ORS + gelatin tannate pediatric patients with acute diarrhea. Rev Esp Enferm Dig. 2009;101:41–48.PubMedCrossRefGoogle Scholar
  4. 4.
    Loeb H, Vandenplas Y, Würsch P, Guesry P. Tannin-rich carob pod for the treatment of acute-onset diarrhea. J Pediatr Gastroenterol Nutr. 1989;8:480–485.PubMedCrossRefGoogle Scholar
  5. 5.
    Plein K, Burkard G, Hotz J. Treatment of chronic diarrhea in Crohn disease. A pilot study of the clinical effect of tannin albuminate and ethacridine lactate. Fortschr Med. 1993;111:114–118.PubMedGoogle Scholar
  6. 6.
    Ziegenhagen DJ, Raedsch R, Kruis W. Traveler’s diarrhea in Turkey. Prospective randomized therapeutic comparison of charcoal versus tannin albuminate/ethacridine lactate. Med Klin (Munich). 1992;87:637–639.Google Scholar
  7. 7.
    Gabriel SE, Davenport SE, Steagall RJ, Vimal V, Carlson T, Rozhon EJ. A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion. Am J Physiol. 1999;276:G58–G63.PubMedGoogle Scholar
  8. 8.
    Wongsamitkul N, Sirianant L, Muanprasat C, Chatsudthipong V. A plant-derived hydrolysable tannin inhibits CFTR chloride channel: a potential treatment of diarrhea. Pharm Res. 2010;27:490–497.PubMedCrossRefGoogle Scholar
  9. 9.
    Schuier M, Sies H, Illek B, Fischer H. Cocoa-related flavonoids inhibit CFTR-mediated chloride transport across T84 human colon epithelia. J Nutr. 2005;135:2320–2325.PubMedGoogle Scholar
  10. 10.
    Namkung W, Thiagarajah JR, Phuan PW, Verkman AS. Inhibition of Ca2+-activated Cl channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. FASEB J. 2010;24:4178–4186.PubMedCrossRefGoogle Scholar
  11. 11.
    van Ampting MT, Schonewille AJ, Vink C, Brummer RJ, van der Meer R, Bovee-Oudenhoven IM. Damage to the intestinal epithelial barrier by antibiotic pretreatment of salmonella-infected rats is lessened by dietary calcium or tannic acid. J Nutr. 2010;140:2167–2172.PubMedCrossRefGoogle Scholar
  12. 12.
    Chen CH, Liu TZ, Chen CH, Wong CH, Chen CH, Lu FJ, Chen SC. The efficacy of protective effects of tannic acid, gallic acid, ellagic acid, and propyl gallate against hydrogen peroxide-induced oxidative stress and DNA damages in IMR-90 cells. Mol Nutr Food Res. 2007;51:962–968.PubMedCrossRefGoogle Scholar
  13. 13.
    Tikoo K, Tamta A, Ali IY, Gupta J, Gaikwad AB. Tannic acid prevents azidothymidine (AZT) induced hepatotoxicity and genotoxicity along with change in expression of PARG and histone H3 acetylation. Toxicol Lett. 2008;177:90–96.PubMedCrossRefGoogle Scholar
  14. 14.
    Seth A, Sheth P, Elias BC, Rao R. Protein phosphatases 2A and 1 interact with occludin and negatively regulate the assembly of tight junctions in the CACO-2 cell monolayer. J Biol Chem. 2007;282:11487–11498.PubMedCrossRefGoogle Scholar
  15. 15.
    Li C, Krishnamurthy PC, Penmatsa H, Marrs KL, Wang XQ, Zaccolo M, Jalink K, Li M, Nelson DJ, Schuetz JD, Naren AP. Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in the gut epithelia. Cell. 2007;131:940–951.PubMedCrossRefGoogle Scholar
  16. 16.
    Apak R, Güçlü K, Demirata B, Ozyürek M, Celik SE, Bektaşoğlu B, Berker KI, Ozyurt D. Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules. 2007;19:1496–1547.CrossRefGoogle Scholar
  17. 17.
    Clayburgh DR, Barrett TA, Tang Y, Meddings JB, Van Eldik LJ, Watterson DM, Clarke LL, Mrsny RJ, Turner JR. Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo. J Clin Invest. 2005;115:2702–2715.PubMedCrossRefGoogle Scholar
  18. 18.
    Graham WV, Marchiando AM, Shen L, Turner JR. No static at all. Ann N Y Acad Sci. 2009;1165:314–322.PubMedCrossRefGoogle Scholar
  19. 19.
    Weflen AW, Alto NM, Hecht GA. Tight junctions and enteropathogenic E. coli. Ann N Y Acad Sci. 2009;1165:169–174.PubMedCrossRefGoogle Scholar
  20. 20.
    Schmitz H, Fromm M, Bentzel CJ, Scholz P, Detjen K, Mankertz J, Bode H, Epple HJ, Riecken EO, Schulzke JD. Tumor necrosis factor-alpha (TNFα) regulates the epithelial barrier in the human intestinal cell line HT-29/B6. J Cell Sci. 1999;112:137–146.PubMedGoogle Scholar
  21. 21.
    Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology. 2000;118:1001–1011.PubMedCrossRefGoogle Scholar
  22. 22.
    Li C, Dandridge KS, Di A, Marrs KL, Harris EL, Roy K, Jackson JS, Makarova NV, Fujiwara Y, Farrar PL, Nelson DJ, Tigyi GJ, Naren AP. Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions. J Exp Med. 2005;202:975–986.PubMedCrossRefGoogle Scholar
  23. 23.
    Thiagarajah JR, Verkman AS. CFTR pharmacology and its role in intestinal fluid secretion. Curr Opin Pharmacol. 2003;3:594–599.PubMedCrossRefGoogle Scholar
  24. 24.
    Powell DW. Barrier function of epithelia. Am J Physiol. 1981;241:G275–G288.PubMedGoogle Scholar
  25. 25.
    Madara JL, Barenberg D, Carlson S. Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity. J Cell Biol. 1986;102:2125–2136.PubMedCrossRefGoogle Scholar
  26. 26.
    Kimura T, Higaki K. Gastrointestinal transit and drug absorption. Biol Pharm Bull. 2002;25:149–164.PubMedCrossRefGoogle Scholar
  27. 27.
    Nieto N, López-Pedrosa JM, Mesa MD, Torres MI, Fernández MI, Ríos A, Suárez MD, Gil A. Chronic diarrhea impairs intestinal antioxidant defense system in rats at weaning. Dig Dis Sci. 2000;45:2044–2050.PubMedCrossRefGoogle Scholar
  28. 28.
    Martín AR, Villegas I, Sánchez-Hidalgo M, de la Lastra CA. The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Br J Pharmacol. 2006;147:873–885.PubMedCrossRefGoogle Scholar
  29. 29.
    Souza SM, Aquino LC, Milach AC Jr, Bandeira MA, Nobre ME, Viana GS. Antiinflammatory and antiulcer properties of tannins from Myracrodruon urundeuva Allemão (Anacardiaceae) in rodents. Phytother Res. 2007;21:220–225.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Aixia Ren
    • 1
  • Weiqiang Zhang
    • 1
  • Hugh Greg Thomas
    • 2
  • Amy Barish
    • 2
  • Stephen Berry
    • 2
  • Jeffrey S. Kiel
    • 2
  • Anjaparavanda P. Naren
    • 1
  1. 1.Department of PhysiologyUniversity of Tennessee Health Science CenterMemphisUSA
  2. 2.Hall Bioscience CorporationFlowery BranchUSA

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