Food Science and Biotechnology

, Volume 25, Issue 1, pp 253–260 | Cite as

Chlorogenic acid decreased intestinal permeability and ameliorated intestinal injury in rats via amelioration of mitochondrial respiratory chain dysfunction

  • Yan Zhou
  • Zheng RuanEmail author
  • Lili Zhou
  • Yuhui Yang
  • Shumei Mi
  • Zeyuan Deng
  • Yulong Yin


Chlorogenic acid (CGA), an abundant polyphenol compound in plants, exhibits anti-oxidant effects. The protective effect of CGA in the rat intestine with endotoxin infusion was evaluated. CGA administration ameliorated endotoxin-induced intestinal injury, and decreased the ratio of lactulose/mannitol, the ileum pathological grade, the myeloperoxidase activity in the ileum, and the malondialdehyde content in the ileum and in ileum mitochondria. The small intestine weight, activities of alkaline phosphatase and superoxide dismutase in the ileum, and β-nicotinamide adenine dinucleotide reduce form (NADH) dehydrogenase and succinate dehydrogenase activities in ileum mitochondria were increased. Intestinal permeability was positively correlated with intestinal mitochondrial injury indicated as the level of malondialdehyde in ileum mitochondria, and negatively correlated with NADH dehydrogenase activity. Dietary administration of CGA protected against increased intestinal permeability caused by endotoxin infusion. The protective effect of CGA was probably associated with a decrease in mitochondrial lipid peroxidation levels and an increase in NADH dehydrogenase activity.


Chlorogenic acid intestinal permeability intestinal injury mitochondria respiration chain enzyme 


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  1. 1.
    Groschwitz KR, Hogan SP. Intestinal barrier function: Molecular regulation and disease pathogenesis. J. Allergy Clin. Immun. 124: 3–20 (2009)CrossRefGoogle Scholar
  2. 2.
    Büning C, Geissler N, Prager M, Sturm A, Baumgart DC, Büttner J, Bühner S, Haas V, Lochs H. Increased small intestinal permeability in ulcerative colitis: Rather genetic than environmental and a risk factor for extensive disease? Inflamm. Bowel Dis. 18: 1932–1939 (2012)CrossRefGoogle Scholar
  3. 3.
    Rao RK, Seth A, Sheth P. Recent advances in alcoholic liver disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease. Am. J. Physiol-Gastr. L. 286: G881–G884 (2004)Google Scholar
  4. 4.
    Ammori BJ, Leeder PC, King RF, Barclay GR, Martin IG, Larvin M, McMahon MJ. Early increase in intestinal permeability in patients with severe acute pancreatitis: Correlation with endotoxemia, organ failure, and mortality. J. Gastrointest. Surg. 3: 252–262 (1999)CrossRefGoogle Scholar
  5. 5.
    Lewis K, McKay DM. Metabolic stress evokes decreases in epithelial barrier function. Ann. NY Acad. Sci. 1165: 327–337 (2009)CrossRefGoogle Scholar
  6. 6.
    Kowaltowski AJ, Vercesi AE. Mitochondrial damage induced by conditions of oxidative stress. Free Radical Bio. Med. 26: 463–471 (1999)CrossRefGoogle Scholar
  7. 7.
    Nazli A, Yang PC, Jury J, Howe K, Watson JL, Söderholm JD, Sherman PM, Perdue MH, McKay DM. Epithelia under metabolic stress perceive commensal bacteria as a threat. Am. J. Pathol. 164: 947–957 (2004)CrossRefGoogle Scholar
  8. 8.
    Sifroni KG, Damiani CR, Stoffel C, Cardoso MR, Ferreira GK, Jeremias IC, Rezin GT, Scaini G, Schuck PF, Dal-Pizzol F, Streck EL. Mitochondrial respiratory chain in the colonic mucosal of patients with ulcerative colitis. Mol. Cell. Biochem. 342: 111–115 (2010)CrossRefGoogle Scholar
  9. 9.
    Taha R, Seidman E, Mailhot G, Boudreau F, Gendron FP, Beaulieu JF, Ménard D, Delvin E, Amre D, Levy E. Oxidative stress and mitochondrial functions in the intestinal Caco-2/15 cell line. PLoS ON. 5: e11817 (2010)CrossRefGoogle Scholar
  10. 10.
    Carrasco-Pozo C, Gotteland M, Speisky H. Apple peel polyphenol extract protects against indomethacin-induced damage in Caco-2 cells by preventing mitochondrial complex I inhibition. J. Agr. Food Chem. 59: 11501–11508 (2011)CrossRefGoogle Scholar
  11. 11.
    Valenti D, De Rasmo D, Signorile A, Rossi L, de Bari L, Scala I, Granese B, Papa S, Vacca RA. Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down's syndrome. BBA-Mol. Basis. Dis. 1832: 542–552 (2013)CrossRefGoogle Scholar
  12. 12.
    Clifford MN. Chlorogenic acids and other cinnamates-nature, occurrence and dietary burden. J. Sci. Food Agr. 79: 362–372 (1999)CrossRefGoogle Scholar
  13. 13.
    Xu Y, Chen J, Yu X, Tao W, Jiang F, Yin Z, Liu C. Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice. Inflamm. Res. 59: 871–877 (2010)CrossRefGoogle Scholar
  14. 14.
    Shan J, Fu J, Zhao Z, Kong X, Huang H, Luo L, Yin Z. Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in RAW264.7 cells through suppressing NF-κB and JNK/AP-1 activation. Int. Immunopharmacol. 9: 1042–1048 (2009)CrossRefGoogle Scholar
  15. 15.
    Rodriguez de Sotillo DV, Hadley M. Chlorogenic acid modifies plasma and liver concentrations of: cholesterol, triacylglycerol, and minerals in (fa/fa) Zucker rats. J. Nutr. Biochem. 13: 717–726 (2002)CrossRefGoogle Scholar
  16. 16.
    Shin HS, Satsu H, Bae MJ, Zhao Z, Ogiwara H, Totsuka M, Shimizu M. Antiinflammatory effect of chlorogenic acid on the IL-8 production in Caco-2 cells and the dextran sulphate sodium-induced colitis symptoms in C57BL/6 mice. Food Chem. 168: 167–175 (2015)CrossRefGoogle Scholar
  17. 17.
    Kobroob A, Chattipakorn N, Wongmekiat O. Caffeic acid phenethyl ester ameliorates cadmium-induced kidney mitochondrial injury. Chem.-Biol. Interact. 200: 21–27 (2012)CrossRefGoogle Scholar
  18. 18.
    Valoti M, Morón JA, Benocci A, Sgaragli G, Unzeta M. Evidence of a coupled mechanism between monoamine oxidase and peroxidase in the metabolism of tyramine by rat intestinal mitochondria. Biochem. Pharmacol. 55: 37–43 (1998)CrossRefGoogle Scholar
  19. 19.
    Ruan Z, Liu S, Zhou Y, Mi S, Liu G, Wu X, Yao K, Assaad H, Deng Z, Hou Y, Wu G, Yin Y. Chlorogenic acid decreases intestinal permeability and increases expression of intestinal tight junction proteins in weaned rats challenged with LPS. PLos ON. 9: e97815 (2014)CrossRefGoogle Scholar
  20. 20.
    Ruan Z, Yang Y, Wen Y, Zhou Y, Fu X, Ding S, Liu G, Yao K, Wu X, Deng Z, Wu G, Yin Y. Metabolomic analysis of amino acid and fat metabolism in rats with Ltryptophan administration. Amino Acid. 46: 2681–2691 (2014)CrossRefGoogle Scholar
  21. 21.
    Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states: I. A morphological, hemodynamic, and metabolic reappraisal. Arch. Surg.-Chicag. 101: 478–483 (1970)CrossRefGoogle Scholar
  22. 22.
    Singer TP. Determination of the Activity of Succinate, NADH, Choline, and α-Glycerophosphate Dehydrogenases. Method. Biochem. Anal. 22: 123–175 (1974)CrossRefGoogle Scholar
  23. 23.
    Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J. Invest. Dermatol. 78: 206–209 (1982)CrossRefGoogle Scholar
  24. 24.
    Poelstra K, Bakker WW, Klok PA, Kamps JA, Hardonk MJ, Meijer DK. Dephosphorylation of endotoxin by alkaline phosphatase in vivo. Am. J. Pathol. 151: 1163 (1997)Google Scholar
  25. 25.
    Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol. 4: 430–435 (1996)CrossRefGoogle Scholar
  26. 26.
    Purohit V, Bode JC, Bode C, Brenner DA, Choudhry MA, Hamilton F, Kang YJ, Keshavarzian A, Rao R, Sartor RB, Swanson C, Turner JR. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcoho. 42: 349–361 (2008)CrossRefGoogle Scholar
  27. 27.
    Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis P, Flint HJ. Human colonic microbiota associated with diet, obesity and weight loss. Int. J. Obesit. 32: 1720–1724 (2008)CrossRefGoogle Scholar
  28. 28.
    O'Dwyer ST, Michie HR, Ziegler TR, Revhaug A, Smith RJ, Wilmore DW. A single dose of endotoxin increases intestinal permeability in healthy humans. Arch. Surg.-Chicag. 123: 1459–1464 (1988)CrossRefGoogle Scholar
  29. 29.
    Mangell P, Mihaescu A, Wang Y, Schramm R, Jeppsson B, Thorlacius H. Critical role of P-selectin-dependent leukocyte recruitment in endotoxin-induced intestinal barrier dysfunction in mice. Inflamm. Res. 56: 189–194 (2007)CrossRefGoogle Scholar
  30. 30.
    Zhou Q, Zhang B, Verne GN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pai. 146: 41–46 (2009)CrossRefGoogle Scholar
  31. 31.
    Campbell EL, MacManus CF, Kominsky DJ, Keely S, Glover LE, Bowers BE, Scully M, Bruyninckx WJ, Colgan SP. Resolvin E1-induced intestinal alkaline phosphatase promotes resolution of inflammation through LPS detoxification. P. Natl. Acad. Sci. US. 107: 14298–14303 (2010)CrossRefGoogle Scholar
  32. 32.
    Kowaltowski AJ, Castilho RF, Vercesi AE. Mitochondrial permeability transition and oxidative stress. FEBS Lett. 495: 12–15 (2001)CrossRefGoogle Scholar
  33. 33.
    Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, Pakay JL, Parker, N. Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radical Bio. Med. 37: 755–767 (2004)CrossRefGoogle Scholar
  34. 34.
    Unno N, Wang H, Menconi MJ, Tytgat SH, Larkin V, Smith M, Morin MJ, Chavez A, Hodin RA, Fink MP. Inhibition of inducible nitric oxide synthase ameliorates endotoxin-induced gut mucosal barrier dysfunction in rats. Gastroenterolog. 113: 1246–1257 (1997)CrossRefGoogle Scholar
  35. 35.
    Crouser ED, Julian MW, Blaho DV, Pfeiffer DR. Endotoxin-induced mitochondrial damage correlates with impaired respiratory activity. Crit. Care Med. 30: 276–284 (2002)CrossRefGoogle Scholar
  36. 36.
    Uraz S, Tahan G, Aytekin H, Tahan V. N-acetylcysteine expresses powerful antiinflammatory and antioxidant activities resulting in complete improvement of acetic acid-induced colitis in rats. Scand. J. Clin. Lab. Inv. 73: 61–66 (2013)CrossRefGoogle Scholar
  37. 37.
    Zhou QQ, Yang DZ, Luo YJ, Li SZ, Liu FY, Wang GS. Over-starvation aggravates intestinal injury and promotes bacterial and endotoxin translocation under high-altitude hypoxic environment. World J. Gastroentero. 17: 1584 (2011)CrossRefGoogle Scholar
  38. 38.
    Song P, Zhang R, Wang X, He P, Tan L, Ma X. Dietary grape-seed procyanidins decreased postweaning diarrhea by modulating intestinal permeability and suppressing oxidative stress in rats. J. Agr. Food Chem. 59: 6227–6232 (2011).CrossRefGoogle Scholar
  39. 39.
    Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS ON. 6: e28032 (2011)CrossRefGoogle Scholar
  40. 40.
    Wang A, Keita ÅV, Phan V, McKay CM, Schoultz I, Lee J, Murphy MP, Fernando M, Ronaghan N, Balce D, Yates R, Dicay M, Beck PL, MacNaughton WK, Söderholm JD, McKay DM. Targeting mitochondria-derived reactive oxygen species to reduce epithelial barrier dysfunction and colitis. Am. J. Pathol. 184: 2516–2527 (2014)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Yan Zhou
    • 1
    • 2
  • Zheng Ruan
    • 1
    • 2
    Email author
  • Lili Zhou
    • 1
    • 2
  • Yuhui Yang
    • 1
    • 2
  • Shumei Mi
    • 1
    • 2
  • Zeyuan Deng
    • 1
    • 2
  • Yulong Yin
    • 1
    • 2
    • 3
  1. 1.State Key Laboratory of Food Science and TechnologyNanchang UniversityNanchangChina
  2. 2.School of Food Science and TechnologyNanchang UniversityNanchangChina
  3. 3.Institute of Subtropical AgricultureChinese Academy of SciencesChangshaChina

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