Natural polyphenols for the prevention of irritable bowel syndrome: molecular mechanisms and targets; a comprehensive review

  • Nazanin Momeni Roudsari
  • Naser-Aldin Lashgari
  • Saeideh Momtaz
  • Mohammad Hosein FarzaeiEmail author
  • André M. Marques
  • Amir Hossein AbdolghaffariEmail author
Review article


Irritable bowel syndrome (IBS) is a well diagnosed disease, thoroughly attributed to series of symptoms criteria that embrace a broad range of abdominal complainers. Such criteria help to diagnosis the disease and can guide controlled clinical trials to seek new therapeutic agents. Accordingly, a verity of mechanisms and pathophysiological conditions including inflammation, oxidative stress, lipid peroxidation and different life styles are involved in IBS. Predictably, diverse therapeutic approaches are available and prescribed by clinicians due to major manifestations (i.e., diarrhea-predominance, constipation-predominance, abdominal pain and visceral hypersensitivity), psychological disturbances, and patient preferences between herbal treatments versus pharmacological therapies, dietary or microbiological approaches. Herein, we gathered the latest scientific data between 1973 and 2019 from databases such as PubMed, Google Scholar, Scopus and Cochrane library on relevant studies concerning beneficial effects of herbal treatments for IBS, in particular polyphenols. This is concluded that polyphenols might be applicable for preventing IBS and improving the IBS symptoms, mainly through suppressing the inflammatory signaling pathways, which nowadays are known as novel platform for the IBS management.


Gastroenterology Irritable bowel syndrome Mechanism Inflammation and oxidative stress Herbal therapy Polyphenols 



  1. 1.
    Wessely S, White PD. There is only one functional somatic syndrome. Br J Psychiatry. 2004;185(2):95–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Mayer EA. Irritable bowel syndrome. N Engl J Med. 2008;358(16):1692–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Spiegel B, et al. Predictors of patient-assessed illness severity in irritable bowel syndrome. Am J Gastroenterol. 2008;103(10):2536.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Trinkley KE, Nahata MC. Treatment of irritable bowel syndrome. J Clin Pharm Ther. 2011;36(3):275–82.CrossRefPubMedGoogle Scholar
  5. 5.
    Longstreth GF, et al. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91.CrossRefPubMedGoogle Scholar
  6. 6.
    Spiegel BM, et al. Is irritable bowel syndrome a diagnosis of exclusion?: a survey of primary care providers, gastroenterologists, and IBS experts. Am J Gastroenterol. 2010;105(4):848.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mearin F, Lacy BE. Diagnostic criteria in IBS: useful or not? Neurogastroenterol Motil. 2012;24(9):791–801.CrossRefPubMedGoogle Scholar
  8. 8.
    Whitehead WE, Drossman DA. Validation of symptom-based diagnostic criteria for irritable bowel syndrome: a critical review. Am J Gastroenterol. 2010;105(4):814.CrossRefPubMedGoogle Scholar
  9. 9.
    Whitehead W, et al. Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome. Aliment Pharmacol Ther. 2006;24(1):137–46.CrossRefPubMedGoogle Scholar
  10. 10.
    Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol. 2014;6:71–80.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Lovell, R.M. and A.C. Ford, Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol, 2012. 10(7): p. 712–721.e4.Google Scholar
  12. 12.
    Pauls R, Max J. Symptoms and dietary practices of irritable bowel syndrome patients compared to controls: results of a USA national survey. Minerva Gastroenterol Dietol. 2019;65(1):1–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Jones MP, et al. Development and initial validation of a measure of perceived stigma in irritable bowel syndrome. Psychol Health Med. 2009;14(3):367–74.CrossRefPubMedGoogle Scholar
  14. 14.
    Dancey C, et al. Perceived stigma, illness intrusiveness and quality of life in men and women with irritable bowel syndrome. Psychol Health Med. 2002;7(4):381–95.CrossRefGoogle Scholar
  15. 15.
    Nettleton S. ‘I just want permission to be ill’: towards a sociology of medically unexplained symptoms. Soc Sci Med. 2006;62(5):1167–78.CrossRefPubMedGoogle Scholar
  16. 16.
    Farmer J, et al. Rural/urban differences in accounts of patients’ initial decisions to consult primary care. Health Place. 2006;12(2):210–21.CrossRefPubMedGoogle Scholar
  17. 17.
    Cummings KM, Becker MH, Maile MC. Bringing the models together: an empirical approach to combining variables used to explain health actions. J Behav Med. 1980;3(2):123–45.CrossRefPubMedGoogle Scholar
  18. 18.
    Zola IK. Pathways to the doctor—from person to patient. Soc Sci Med (1967). 1973;7(9):677–89.CrossRefGoogle Scholar
  19. 19.
    Cann P, et al. Role of loperamide and placebo in management of irritable bowel syndrome (IBS). Dig Dis Sci. 1984;29(3):239–47.CrossRefPubMedGoogle Scholar
  20. 20.
    Efskind P, Bernklev T, Vatn M. A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol. 1996;31(5):463–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Pasricha PJ. Desperately seeking serotonin… a commentary on the withdrawal of tegaserod and the state of drug development for functional and motility disorders. Gastroenterology. 2007;132(7):2287–90.CrossRefPubMedGoogle Scholar
  22. 22.
    Abbas Z, et al. Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: a randomized trial. Eur J Gastroenterol Hepatol. 2014;26(6):630–9.PubMedGoogle Scholar
  23. 23.
    Trinkley KE, Nahata MC. Medication management of irritable bowel syndrome. Digestion. 2014;89(4):253–67.CrossRefPubMedGoogle Scholar
  24. 24.
    Kułak-Bejda A, Bejda G, Waszkiewicz N. Antidepressants for irritable bowel syndrome—a systematic review. Pharmacol Rep. 2017;69(6):1366–79.CrossRefPubMedGoogle Scholar
  25. 25.
    Clouse R. Antidepressants for irritable bowel syndrome. Gut. 2003;52(4):598–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Nee J, Zakari M, Lembo AJ. Novel therapies in IBS-D treatment. Curr Treat Options Gastroenterol. 2015;13(4):432–40.CrossRefPubMedGoogle Scholar
  27. 27.
    Lee K, Kim J, Cho S. Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2005;22(10):981–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Crofford LJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52(4):1264–73.CrossRefPubMedGoogle Scholar
  29. 29.
    Goldenberg DL. Pain/depression dyad: a key to a better understanding and treatment of functional somatic syndromes. Am J Med. 2010;123(8):675–82.CrossRefPubMedGoogle Scholar
  30. 30.
    Häuser W, Petzke F, Sommer C. Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome. J Pain. 2010;11(6):505–21.CrossRefPubMedGoogle Scholar
  31. 31.
    Whorwell PJ, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101(7):1581.CrossRefPubMedGoogle Scholar
  32. 32.
    Enck P, et al. Randomized controlled treatment trial of irritable bowel syndrome with a probiotic E.-coli preparation (DSM17252) compared to placebo. Z Gastroenterol. 2009;47(2):209.CrossRefPubMedGoogle Scholar
  33. 33.
    Drouault-Holowacz S, et al. A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome. Gastroenterol Clin Biol. 2008;32(2):147–52.CrossRefPubMedGoogle Scholar
  34. 34.
    Kajander K, et al. Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther. 2008;27(1):48–57.CrossRefPubMedGoogle Scholar
  35. 35.
    O’Mahony L, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128(3):541–51.CrossRefPubMedGoogle Scholar
  36. 36.
    Cappello G, et al. Peppermint oil (Mintoil®) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial. Dig Liver Dis. 2007;39(6):530–6.CrossRefPubMedGoogle Scholar
  37. 37.
    Liu J-H, et al. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol. 1997;32(6):765.CrossRefPubMedGoogle Scholar
  38. 38.
    Evans M, Wotring R. Polyphenol-reactive oxygen species compositions and methods. United States Patent Application 16/143,398.Google Scholar
  39. 39.
    Salah N, et al. Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys. 1995;322(2):339–46.CrossRefPubMedGoogle Scholar
  40. 40.
    Pastoriza S, et al. Healthy properties of green and white teas: an update. Food Funct. 2017;8(8):2650–62.CrossRefPubMedGoogle Scholar
  41. 41.
    Park S-J, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012;148(3):421–33.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Ray NB, et al. Bioactive Olive Oil Polyphenols in the promotion of health. The role of functional food security in global health. Cambridge: Academic Press; 2019. p. 623–7.Google Scholar
  43. 43.
    Igwe EO, et al. A systematic literature review of the effect of anthocyanins on gut microbiota populations. J Hum Nutr Diet. 2019;32(1):53–62.CrossRefPubMedGoogle Scholar
  44. 44.
    Talbott SM, et al. Effect of coordinated probiotic/prebiotic/phytobiotic supplementation on microbiome balance and psychological mood state in healthy stressed adults. Funct Foods Health Dis. 2019;9(4):265–75.CrossRefGoogle Scholar
  45. 45.
    Nelkowska DD. Importance of personal resources for the quality of life of patients with irritable bowel syndrome (IBS). Journal of Education, Health and Sport. 2019;9(4):442–53.Google Scholar
  46. 46.
    Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Med Cell Longev. 2009;2(5):270–8.CrossRefGoogle Scholar
  47. 47.
    Kondratyuk TP, Pezzuto JM. Natural product polyphenols of relevance to human health. Pharm Biol. 2004;42(sup1):46–63.CrossRefGoogle Scholar
  48. 48.
    Scalbert A, et al. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr. 2005;45(4):287–306.CrossRefPubMedGoogle Scholar
  49. 49.
    Vitrac X, et al. Direct liquid chromatographic analysis of resveratrol derivatives and flavanonols in wines with absorbance and fluorescence detection. Anal Chim Acta. 2002;458(1):103–10.CrossRefGoogle Scholar
  50. 50.
    Barahona MJ, et al. Design and implementation of novel nutraceuticals and derivatives for treating intestinal disorders. Future Med Chem. 2019;11(08):847–55.Google Scholar
  51. 51.
    Spencer JP, et al. Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research. Br J Nutr. 2008;99(1):12–22.CrossRefPubMedGoogle Scholar
  52. 52.
    Luqman S, Rizvi SI. Protection of lipid peroxidation and carbonyl formation in proteins by capsaicin in human erythrocytes subjected to oxidative stress. Phytother Res. 2006;20(4):303–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Pandey KB, Rizvi SI. Protective effect of resveratrol on markers of oxidative stress in human erythrocytes subjected to in vitro oxidative insult. Phytother Res. 2010;24(S1):S11–4.CrossRefPubMedGoogle Scholar
  54. 54.
    Pandey KB, Mishra N, Rizvi SI. Protective role of myricetin on markers of oxidative stress in human erythrocytes subjected to oxidative stress. Nat Prod Commun. 2009;4(2):221–6.PubMedGoogle Scholar
  55. 55.
    Prade RA, et al. Pectins, pectinases and plant-microbe interactions. Biotechnol Genet Eng Rev. 1999;16(1):361–92.CrossRefPubMedGoogle Scholar
  56. 56.
    Sinagra E, et al. Inflammation in irritable bowel syndrome: myth or new treatment target? World J Gastroenterol. 2016;22(7):2242.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Choghakhori R, et al. Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: association with digestive symptoms and quality of life. Cytokine. 2017;93:34–43.CrossRefPubMedGoogle Scholar
  58. 58.
    Kamatou GP, et al. Menthol: a simple monoterpene with remarkable biological properties. Phytochemistry. 2013;96:15–25.CrossRefPubMedGoogle Scholar
  59. 59.
    Yu F-Y, et al. Effects of baicalin in CD4+ CD29+ T cell subsets of ulcerative colitis patients. World J Gastroenterol. 2014;20(41):15299.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Scully P, et al. Plasma cytokine profiles in females with irritable bowel syndrome and extra-intestinal co-morbidity. Am J Gastroenterol. 2010;105(10):2235.CrossRefPubMedGoogle Scholar
  61. 61.
    Schuhmacher A, Reichling J, Schnitzler P. Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro. Phytomedicine. 2003;10(6/7):504.CrossRefPubMedGoogle Scholar
  62. 62.
    Schmulson M, et al. Lower serum IL-10 is an independent predictor of IBS among volunteers in Mexico. Am J Gastroenterol. 2012;107(5):747.CrossRefPubMedGoogle Scholar
  63. 63.
    Collins S, Piche T, Rampal P. The putative role of inflammation in the irritable bowel syndrome. Gut. 2001;49(6):743–5.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Spiller R, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut. 2007;56(12):1770–98.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Hong SW, et al. Aloe vera is effective and safe in short-term treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Neurogastroenterol Motil. 2018;24(4):528–35.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Hughes PA, et al. Sensory neuro-immune interactions differ between irritable bowel syndrome subtypes. Gut. 2013;62(10):1456–65.CrossRefPubMedGoogle Scholar
  67. 67.
    Kline RM, et al. Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children. J Pediatr. 2001;138(1):125–8.CrossRefPubMedGoogle Scholar
  68. 68.
    Bundy R, et al. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study. J Altern Complement Med. 2004;10(6):1015–8.CrossRefPubMedGoogle Scholar
  69. 69.
    Ford AC, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008;337:a2313.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Alt F, et al. Evaluation of benefit and tolerability of IQP-CL-101 (Xanthofen) in the symptomatic improvement of irritable bowel syndrome: a double-blinded, randomised, Placebo-Controlled Clinical Trial. Phytother Res. 2017;31(7):1056–62.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    McIntosh, K., et al., FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut. 2016: p. gutjnl-2015-311339.Google Scholar
  72. 72.
    Jalili M, et al. Co-Administration of soy Isoflavones and Vitamin D in Management of Irritable Bowel Disease. PLoS One. 2016;11(8):e0158545.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    López A, et al. Phenolic constituents, antioxidant and preliminary antimycoplasmic activities of leaf skin and flowers of Aloe vera (L.) Burm. f.(syn. A. barbadensis mill.) from the Canary Islands (Spain). Molecules. 2013;18(5):4942–54.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Portincasa P, et al. Curcumin and fennel essential oil improve symptoms and quality of life in patients with irritable bowel syndrome. J Gastrointest Liver Dis. 2016:25(2).Google Scholar
  75. 75.
    Merat S, et al. The effect of enteric-coated, delayed-release peppermint oil on irritable bowel syndrome. Dig Dis Sci. 2010;55(5):1385–90.CrossRefPubMedGoogle Scholar
  76. 76.
    Davis K, et al. Randomised double-blind placebo-controlled trial of aloe vera for irritable bowel syndrome. Int J Clin Pract. 2006;60(9):1080–6.CrossRefPubMedGoogle Scholar
  77. 77.
    Vázquez B, et al. Antiinflammatory activity of extracts from Aloe vera gel. J Ethnopharmacol. 1996;55(1):69–75.CrossRefPubMedGoogle Scholar
  78. 78.
    Vaziri ND, Rodríguez-Iturbe B. Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension. Nat Rev Nephrol. 2006;2(10):582.CrossRefGoogle Scholar
  79. 79.
    Langmead L, et al. Randomized, double-blind, placebo-controlled trial of oral aloe vera gel for active ulcerative colitis. Aliment Pharmacol Ther. 2004;19(7):739–47.CrossRefPubMedGoogle Scholar
  80. 80.
    Agarwal O. Prevention of atheromatous heart disease. Angiology. 1985;36(8):485–92.CrossRefPubMedGoogle Scholar
  81. 81.
    Mete R, et al. The role of oxidants and reactive nitrogen species in irritable bowel syndrome: a potential etiological explanation. Med Sci Monit. 2013;19:762.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Yeh GY, et al. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003;26(4):1277–94.CrossRefPubMedGoogle Scholar
  83. 83.
    Klein AD, Penneys NS. Aloe vera. J Am Acad Dermatol. 1988;18(4):714–20.CrossRefPubMedGoogle Scholar
  84. 84.
    Choi SW, et al. The wound-healing effect of a glycoprotein fraction isolated from aloe vera. Br J Dermatol. 2001;145(4):535–45.CrossRefPubMedGoogle Scholar
  85. 85.
    Eamlamnam K, et al. Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats. World J Gastroenterol: WJG. 2006;12(13):2034.CrossRefPubMedGoogle Scholar
  86. 86.
    Werawatganon D, et al. Aloe vera attenuated gastric injury on indomethacin-induced gastropathy in rats. World J Gastroenterol: WJG. 2014;20(48):18330.CrossRefPubMedGoogle Scholar
  87. 87.
    Hutchings, H., et al., A randomised, cross-over, placebo-controlled study of Aloe vera in patients with irritable bowel syndrome: effects on patient quality of life. ISRN Gastroenterol, 2010. 2011.Google Scholar
  88. 88.
    Størsrud S, Pontén I, Simrén M. A pilot study of the effect of Aloe barbadensis mill. extract (AVH200®) in patients with irritable bowel syndrome: a randomized, double-blind, placebo-controlled study. J Gastrointestin Liver Dis. 2015;24(3):275–80.PubMedGoogle Scholar
  89. 89.
    Ndhlala A, et al. Antimicrobial, anti-inflammatory and mutagenic investigation of the south African tree aloe (Aloe barberae). J Ethnopharmacol. 2009;124(3):404–8.CrossRefPubMedGoogle Scholar
  90. 90.
    Athiban PP, et al. Evaluation of antimicrobial efficacy of Aloe vera and its effectiveness in decontaminating gutta percha cones. J Conserv Dent. 2012;15(3):246.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Arunkumar S, Muthuselvam M. Analysis of phytochemical constituents and antimicrobial activities of Aloe vera L. against clinical pathogens. World J Agric Sci. 2009;5(5):572–6.Google Scholar
  92. 92.
    Philip J, John S, Iyer P. Antimicrobial activity of aloevera barbedensis, daucus carota, emblica officinalis, honey and punica granatum and formulation of a health drink and salad. Malays J Microbiol. 2012;8(3):141–147p.Google Scholar
  93. 93.
    Alemdar S, Agaoglu S. Investigation of in vitro antimicrobial activity of Aloe vera juice. J Anim Vet Adv. 2009;8(1):99–102.Google Scholar
  94. 94.
    Cock IE. Antimicrobial activity of Aloe barbadensis miller leaf gel components. Internet J Microbiol. 2008;4(2):17.Google Scholar
  95. 95.
    Hu Y, Xu J, Hu Q. Evaluation of antioxidant potential of Aloe vera (Aloe barbadensis miller) extracts. J Agric Food Chem. 2003;51(26):7788–91.CrossRefPubMedGoogle Scholar
  96. 96.
    Fani M, Kohanteb J. Inhibitory activity of Aloe vera gel on some clinically isolated cariogenic and periodontopathic bacteria. J Oral Sci. 2012;54(1):15–21.CrossRefPubMedGoogle Scholar
  97. 97.
    Martínez C, et al. The jejunum of diarrhea-predominant irritable bowel syndrome shows molecular alterations in the tight junction signaling pathway that are associated with mucosal pathobiology and clinical manifestations. Am J Gastroenterol. 2012;107(5):736.CrossRefPubMedGoogle Scholar
  98. 98.
    Ceriello A, et al. Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress. Diabetologia. 2001;44(7):834–8.CrossRefPubMedGoogle Scholar
  99. 99.
    Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615–25.CrossRefPubMedGoogle Scholar
  100. 100.
    Shyur L-F, et al. Antioxidant properties of extracts from medicinal plants popularly used in Taiwan. Int J Appl Sci Eng. 2005;3(3):195–202.Google Scholar
  101. 101.
    Langmead L, Makins R, Rampton D. Anti-inflammatory effects of aloe vera gel in human colorectal mucosa in vitro. Aliment Pharmacol Ther. 2004;19(5):521–7.CrossRefPubMedGoogle Scholar
  102. 102.
    Yordi, E.G., et al., Antioxidant and pro-oxidant effects of polyphenolic compounds and structure-activity relationship evidence, in Nutrition, well-being and health 2012, InTech.Google Scholar
  103. 103.
    Sparks M, et al. Does peppermint oil relieve spasm during barium enema? Br J Radiol. 1995;68(812):841–3.CrossRefPubMedGoogle Scholar
  104. 104.
    Asao T, et al. Spasmolytic effect of peppermint oil in barium during double-contrast barium enema compared with Buscopan. Clin Radiol. 2003;58(4):301–5.CrossRefPubMedGoogle Scholar
  105. 105.
    May B, et al. Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia. Arzneimittelforschung. 1996;46(12):1149–53.PubMedGoogle Scholar
  106. 106.
    Göbel H, et al. Effectiveness of oleum menthae piperitae and paracetamol in therapy of headache of the tension type. Nervenarzt. 1996;67(8):672–81.CrossRefPubMedGoogle Scholar
  107. 107.
    Yu Y, et al. The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome: involvement of 5-HT-dependent signaling. Metab Brain Dis. 2015;30(1):47–55.CrossRefPubMedGoogle Scholar
  108. 108.
    Xu, Y., et al., trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis. Front Pharmacol. 2018. 9.Google Scholar
  109. 109.
    Mao Q, et al. Chemical profiles and pharmacological activities of Chang-Kang-fang, a multi-herb Chinese medicinal formula, for treating irritable bowel syndrome. J Ethnopharmacol. 2017;201:123–35.CrossRefPubMedGoogle Scholar
  110. 110.
    Micucci M, et al. Newer insights into the antidiarrheal effects of Acacia catechu Willd. Extract in Guinea pig. J Med Food. 2017;20(6):592–600.CrossRefPubMedGoogle Scholar
  111. 111.
    Chen Q, et al. A novel prebiotic blend product prevents irritable bowel syndrome in mice by improving gut microbiota and modulating immune response. Nutrients. 2017;9(12):1341.CrossRefPubMedCentralGoogle Scholar
  112. 112.
    Hawthorn M, et al. The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations. Aliment Pharmacol Ther. 1988;2(2):101–18.CrossRefPubMedGoogle Scholar
  113. 113.
    Hills JM, Aaronson PI. The mechanism of action of peppermint oil on gastrointestinal smooth muscle: an analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and Guinea pig. Gastroenterology. 1991;101(1):55–65.CrossRefPubMedGoogle Scholar
  114. 114.
    Walstab J, et al. Natural compounds boldine and menthol are antagonists of human 5-HT 3 receptors: implications for treating gastrointestinal disorders. Neurogastroenterol Motil. 2014;26(6):810–20.CrossRefPubMedGoogle Scholar
  115. 115.
    Galeotti N, et al. Menthol: a natural analgesic compound. Neurosci Lett. 2002;322(3):145–8.CrossRefPubMedGoogle Scholar
  116. 116.
    Harries N, James K, Pugh W. Antifoaming and carminative actions of volatile oils. J Clin Pharm Ther. 1977;2(3):171–7.CrossRefGoogle Scholar
  117. 117.
    Myers SR, Hawrelak J, Cattley T. Essential oils in the treatment of intestinal dysbiosis: a preliminary in vitro study. Altern Med Rev. 2009;14(4):380–4.PubMedGoogle Scholar
  118. 118.
    Juergens U, Stöber M, Vetter H. The anti-inflammatory activity of L-menthol compared to mint oil in human monocytes in vitro: a novel perspective for its therapeutic use in inflammatory diseases. Eur J Med Res. 1998;3(12):539–45.PubMedGoogle Scholar
  119. 119.
    Enck P, et al. Therapy options in irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2010;22(12):1402–11.PubMedGoogle Scholar
  120. 120.
    Cash BD, Epstein MS, Shah SM. A novel delivery system of peppermint oil is an effective therapy for irritable bowel syndrome symptoms. Dig Dis Sci. 2016;61(2):560–71.CrossRefPubMedGoogle Scholar
  121. 121.
    Amato A, Liotta R, Mulè F. Effects of menthol on circular smooth muscle of human colon: analysis of the mechanism of action. Eur J Pharmacol. 2014;740:295–301.CrossRefPubMedGoogle Scholar
  122. 122.
    Kim HJ, et al. Menthol modulates pacemaker potentials through TRPA1 channels in cultured interstitial cells of cajal from murine small intestine. Cell Physiol Biochem. 2016;38(5):1869–82.CrossRefPubMedGoogle Scholar
  123. 123.
    Atta A, Alkofahi A. Anti-nociceptive and anti-inflammatory effects of some Jordanian medicinal plant extracts. J Ethnopharmacol. 1998;60(2):117–24.CrossRefPubMedGoogle Scholar
  124. 124.
    Karashima Y, et al. Bimodal action of menthol on the transient receptor potential channel TRPA1. J Neurosci. 2007;27(37):9874–84.CrossRefPubMedGoogle Scholar
  125. 125.
    Ghasemi-Pirbaluti M, Motaghi E, Bozorgi H. The effect of menthol on acute experimental colitis in rats. Eur J Pharmacol. 2017;805:101–7.CrossRefPubMedGoogle Scholar
  126. 126.
    Perraud A-L, Knowles H, Schmitz C. Novel aspects of signaling and ion-homeostasis regulation in immunocytes: the TRPM ion channels and their potential role in modulating the immune response. Mol Immunol. 2004;41(6–7):657–73.CrossRefPubMedGoogle Scholar
  127. 127.
    Ramachandran R, et al. TRPM8 activation attenuates inflammatory responses in mouse models of colitis. Proc Natl Acad Sci. 2013;110(18):7476–81.CrossRefPubMedGoogle Scholar
  128. 128.
    Lü JM, et al. Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med. 2010;14(4):840–60.CrossRefPubMedGoogle Scholar
  129. 129.
    Nejatzadeh-Barandozi F. Antibacterial activities and antioxidant capacity of Aloe vera. Org Med Chem Lett. 2013;3(1):5.CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Rodriguez TS, Giménez DG, De la Puerta Vázquez R. Choleretic activity and biliary elimination of lipids and bile acids induced by an artichoke leaf extract in rats. Phytomedicine. 2002;9(8):687–93.CrossRefGoogle Scholar
  131. 131.
    Wegener T, Fintelmann V. Pharmacological properties and therapeutic profile of artichoke (Cynara scolymus L.). Wien Med Wochenschr (1946). 1999;149(8–10):241–7.Google Scholar
  132. 132.
    Emendorfer F, et al. Evaluation of the relaxant action of some Brazilian medicinal plants in isolated Guinea-pig ileum and rat duodenum. J Pharm Pharm Sci. 2005;8(1):63–8.PubMedGoogle Scholar
  133. 133.
    Asif M. Phytochemical study of polyphenols in Perilla Frutescens as an antioxidant. Avicenna J Phytomed. 2012;2(4):169.PubMedPubMedCentralGoogle Scholar
  134. 134.
    Rahimi R, Abdollahi M. Herbal medicines for the management of irritable bowel syndrome: a comprehensive review. World J Gastroenterol: WJG. 2012;18(7):589.CrossRefPubMedGoogle Scholar
  135. 135.
    Corazziari E, et al. Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2003;18(6):569–80.CrossRefPubMedGoogle Scholar
  136. 136.
    Tian J, et al. Regional variation in components and antioxidant and antifungal activities of Perilla frutescens essential oils in China. Ind Crop Prod. 2014;59:69–79.CrossRefGoogle Scholar
  137. 137.
    Verspohl EJ, et al. Testing of Perilla frutescens extract and Vicenin 2 for their antispasmodic effect. Phytomedicine. 2013;20(5):427–31.CrossRefPubMedGoogle Scholar
  138. 138.
    Buchwald-Werner S, et al. Perilla extract improves gastrointestinal discomfort in a randomized placebo controlled double blind human pilot study. BMC Complement Altern Med. 2014;14(1):173.CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Yang F, et al. The green tea polyphenol (−)-epigallocatechin-3-gallate blocks nuclear factor-κB activation by inhibiting IκB kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol. 2001;60(3):528–33.PubMedGoogle Scholar
  140. 140.
    Walker AF, Middleton RW, Petrowicz O. Artichoke leaf extract reduces symptoms of irritable bowel syndrome in a post-marketing surveillance study. Phytother Res. 2001;15(1):58–61.CrossRefPubMedGoogle Scholar
  141. 141.
    Bundy R, et al. Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis. J Altern Complement Med. 2004;10(4):667–9.CrossRefPubMedGoogle Scholar
  142. 142.
    Nanjo F, et al. Scavenging effects of tea catechins and their derivatives on 1, 1-diphenyl-2-picrylhydrazyl radical. Free Radic Biol Med. 1996;21(6):895–902.CrossRefPubMedGoogle Scholar
  143. 143.
    Khokhar S, Magnusdottir S. Total phenol, catechin, and caffeine contents of teas commonly consumed in the United Kingdom. J Agric Food Chem. 2002;50(3):565–70.CrossRefPubMedGoogle Scholar
  144. 144.
    Jeong JH, et al. Epigallocatechin 3-gallate attenuates neuronal damage induced by 3-hydroxykynurenine. Toxicology. 2004;195(1):53–60.CrossRefPubMedGoogle Scholar
  145. 145.
    Levites Y, et al. Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-κB) activation and cell death by tea extracts in neuronal cultures1. Biochem Pharmacol. 2002;63(1):21–9.Google Scholar
  146. 146.
    Lin Y-L, Lin J-K. (−)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-κB. Mol Pharmacol. 1997;52(3):465–72.CrossRefPubMedGoogle Scholar
  147. 147.
    Levites Y, et al. Green tea polyphenol (−)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced dopaminergic neurodegeneration. J Neurochem. 2001;78(5):1073–82.CrossRefPubMedGoogle Scholar
  148. 148.
    Barthelman M, et al. (−)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity. Carcinogenesis. 1998;19(12):2201–4.CrossRefPubMedGoogle Scholar
  149. 149.
    Wheeler DS, et al. Epigallocatechin-3-gallate, a green tea–derived polyphenol, inhibits IL-1β-dependent proinflammatory signal transduction in cultured respiratory epithelial cells. J Nutr. 2004;134(5):1039–44.CrossRefPubMedGoogle Scholar
  150. 150.
    Veres, B., Anti-inflammatory role of natural polyphenols and their degradation products, in Severe Sepsis and Septic Shock-Understanding a Serious Killer 2012. InTech.Google Scholar
  151. 151.
    Shin H-Y, et al. Epigallocatechin-3-gallate inhibits secretion of TNF-α, IL-6 and IL-8 through the attenuation of ERK and NF-κB in HMC-1 cells. Int Arch Allergy Immunol. 2007;142(4):335–44.CrossRefPubMedGoogle Scholar
  152. 152.
    Youn HS, et al. Suppression of MyD88-and TRIF-dependent signaling pathways of toll-like receptor by (−)-epigallocatechin-3-gallate, a polyphenol component of green tea. Biochem Pharmacol. 2006;72(7):850–9.Google Scholar
  153. 153.
    Osuchowski MF, et al. Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality. J Immunol. 2006;177(3):1967–74.CrossRefPubMedGoogle Scholar
  154. 154.
    Li W, et al. A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1. PLoS One. 2007;2(11):e1153.CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Heuer JG, et al. Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis. Crit Care Med. 2004;32(7):1570–8.CrossRefPubMedGoogle Scholar
  156. 156.
    Bae H-B, et al. The effect of epigallocatechin gallate on lipopolysaccharide-induced acute lung injury in a murine model. Inflammation. 2010;33(2):82–91.CrossRefPubMedGoogle Scholar
  157. 157.
    Yun H-J, et al. Epigallocatechin-3-gallate suppresses TNF-α-induced production of MMP-1 and-3 in rheumatoid arthritis synovial fibroblasts. Rheumatol Int. 2008;29(1):23–9.CrossRefPubMedGoogle Scholar
  158. 158.
    Ichikawa D, et al. Effect of various catechins on the IL-12p40 production by murine peritoneal macrophages and a macrophage cell line, J774. 1. Biol Pharm Bull. 2004;27(9):1353–8.CrossRefPubMedGoogle Scholar
  159. 159.
    Ouyang P, et al. Green tea polyphenols inhibit advanced glycation end product-induced rat vascular smooth muscle cell proliferation. Di Yi Jun Yi Da Xue Xue Bao. 2004;24(3):247–51.PubMedGoogle Scholar
  160. 160.
    Dekdouk, N., et al., Phenolic compounds from Olea europaea L. possess antioxidant activity and inhibit carbohydrate metabolizing enzymes in vitro. Evid Based Complement Alternat Med, 2015. 2015.Google Scholar
  161. 161.
    Martín-Peláez S, et al. Influence of phenol-enriched olive oils on human intestinal immune function. Nutrients. 2016;8(4):213.CrossRefPubMedPubMedCentralGoogle Scholar
  162. 162.
    Koca U, et al. Wound repair potential of Olea europaea L. leaf extracts revealed by in vivo experimental models and comparative evaluation of the extracts' antioxidant activity. J Med Food. 2011;14(1–2):140–6.CrossRefPubMedGoogle Scholar
  163. 163.
    Larussa T, et al. Oleuropein decreases cyclooxygenase-2 and interleukin-17 expression and attenuates inflammatory damage in colonic samples from ulcerative colitis patients. Nutrients. 2017;9(4):391.CrossRefPubMedCentralGoogle Scholar
  164. 164.
    Jang M, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275(5297):218–20.CrossRefPubMedGoogle Scholar
  165. 165.
    Virgili M, Contestabile A. Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats. Neurosci Lett. 2000;281(2–3):123–6.CrossRefPubMedGoogle Scholar
  166. 166.
    Xu Y, et al. Trans-resveratrol ameliorates stress-induced irritable bowel syndrome-like behaviors by regulation of brain-gut axis. Front Pharmacol. 2018;9:631.CrossRefPubMedPubMedCentralGoogle Scholar
  167. 167.
    Hung L-M, et al. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res. 2000;47(3):549–55.CrossRefPubMedGoogle Scholar
  168. 168.
    Chung JH. Metabolic benefits of inhibiting cAMP-PDEs with resveratrol. Adipocyte. 2012;1(4):256–8.CrossRefPubMedPubMedCentralGoogle Scholar
  169. 169.
    Damián JP, et al. Effect of resveratrol on behavioral Performanceof Streptozotocin-induced diabetic mice inAnxiety tests. Exp Anim. 2014;63(3):277–87.CrossRefPubMedPubMedCentralGoogle Scholar
  170. 170.
    Ge J-F, et al. Resveratrol ameliorates the anxiety-and depression-like behavior of subclinical hypothyroidism rat: possible involvement of the HPT axis, HPA axis, and Wnt/β-catenin pathway. Front Endocrinol. 2016;7:44.CrossRefGoogle Scholar
  171. 171.
    Ali SH, et al. Resveratrol ameliorates depressive-like behavior in repeated corticosterone-induced depression in mice. Steroids. 2015;101:37–42.CrossRefPubMedGoogle Scholar
  172. 172.
    Wang X, et al. Resveratrol reverses chronic restraint stress-induced depression-like behaviour: involvement of BDNF level, ERK phosphorylation and expression of Bcl-2 and Bax in rats. Brain Res Bull. 2016;125:134–43.CrossRefPubMedGoogle Scholar
  173. 173.
    Wang N, et al. Resveratrol protects oxidative stress-induced intestinal epithelial barrier dysfunction by upregulating heme oxygenase-1 expression. Dig Dis Sci. 2016;61(9):2522–34.CrossRefPubMedGoogle Scholar
  174. 174.
    Wang G, et al. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling. Oncotarget. 2016;7(14):17380.PubMedPubMedCentralGoogle Scholar
  175. 175.
    Barnette MS, et al. Initial biochemical and functional characterization of cyclic nucleotide phosphodiesterase isozymes in canine colonic smooth muscle. J Pharmacol Exp Ther. 1993;264(2):801–12.PubMedGoogle Scholar
  176. 176.
    Johansson EM, Reyes-Irisarri E, Mengod G. Comparison of cAMP-specific phosphodiesterase mRNAs distribution in mouse and rat brain. Neurosci Lett. 2012;525(1):1–6.CrossRefPubMedGoogle Scholar
  177. 177.
    Barone FC, et al. Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. Pharmacology. 2008;81(1):11–7.CrossRefPubMedGoogle Scholar
  178. 178.
    Birrell MA, et al. Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-κB-independent mechanism. FASEB J. 2005;19(7):840–1.CrossRefPubMedGoogle Scholar
  179. 179.
    Chung EK, et al. Neonatal maternal separation enhances central sensitivity to noxious colorectal distention in rat. Brain Res. 2007;1153:68–77.CrossRefPubMedGoogle Scholar
  180. 180.
    Belguendouz L, Frémont L, Gozzelino M-T. Interaction of transresveratrol with plasma lipoproteins. Biochem Pharmacol. 1998;55(6):811–6.CrossRefPubMedGoogle Scholar
  181. 181.
    Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol. 2000;164(12):6509–19.CrossRefPubMedGoogle Scholar
  182. 182.
    Surh Y-J, et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κB activation. Mutat Res. 2001;480:243–68.CrossRefPubMedGoogle Scholar
  183. 183.
    Chan MM-Y, et al. Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem Pharmacol. 2000;60(10):1539–48.CrossRefPubMedGoogle Scholar
  184. 184.
    Martinez J, Moreno JJ. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol. 2000;59(7):865–70.CrossRefPubMedGoogle Scholar
  185. 185.
    Moreno JJ. Resveratrol modulates arachidonic acid release, prostaglandin synthesis, and 3T6 fibroblast growth. J Pharmacol Exp Ther. 2000;294(1):333–8.PubMedGoogle Scholar
  186. 186.
    Martin AR, et al. Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. Biochem Pharmacol. 2004;67(7):1399–410.CrossRefPubMedGoogle Scholar
  187. 187.
    Tsai SH, Lin-Shiau SY, Lin JK. Suppression of nitric oxide synthase and the down-regulation of the activation of NFκB in macrophages by resveratrol. Br J Pharmacol. 1999;126(3):673–80.CrossRefPubMedPubMedCentralGoogle Scholar
  188. 188.
    Wadsworth TL, Koop DR. Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochem Pharmacol. 1999;57(8):941–9.CrossRefPubMedGoogle Scholar
  189. 189.
    Kruidenier, L.a. and H. Verspaget, oxidative stress as a pathogenic factor in inflammatory bowel disease—radicals or ridiculous? Aliment Pharmacol Ther, 2002. 16(12): p. 1997–2015.Google Scholar
  190. 190.
    Nitta M, et al. Expression of the EP4 prostaglandin E2 receptor subtype with rat dextran sodium sulphate colitis: colitis suppression by a selective agonist, ONO-AE1-329. Scand J Immunol. 2002;56(1):66–75.CrossRefPubMedGoogle Scholar
  191. 191.
    Abreu MT. The pathogenesis of inflammatory bowel disease: translational implications for clinicians. Curr Gastroenterol Rep. 2002;4(6):481–9.CrossRefPubMedGoogle Scholar
  192. 192.
    Siegmund B. Interleukin-1β converting enzyme (caspase-1) in intestinal inflammation. Biochem Pharmacol. 2002;64(1):1–8.CrossRefPubMedGoogle Scholar
  193. 193.
    Zhong W, et al. Effects of prostaglandin E2, cholera toxin and 8-bromo-cyclic AMP on lipopolysaccharide-induced gene expression of cytokines in human macrophages. Immunology. 1995;84(3):446.PubMedPubMedCentralGoogle Scholar
  194. 194.
    Gonzales AM, Orlando RA. Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes. Nutr Metab. 2008;5(1):17.CrossRefGoogle Scholar
  195. 195.
    Gao X, et al. Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production1. Biochem Pharmacol. 2001;62(9):1299–308.CrossRefPubMedGoogle Scholar
  196. 196.
    Ajuebor MN, Singh A, Wallace JL. Cyclooxygenase-2-derived prostaglandin D2 is an early anti-inflammatory signal in experimental colitis. Am J Physiol Gastrointest Liver Physiol. 2000;279(1):G238–44.CrossRefPubMedGoogle Scholar
  197. 197.
    Sánchez-Fidalgo S, et al. Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice. Eur J Pharmacol. 2010;633(1–3):78–84.CrossRefPubMedGoogle Scholar
  198. 198.
    Culpitt S, et al. Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD. Thorax. 2003;58(11):942–6.CrossRefPubMedPubMedCentralGoogle Scholar
  199. 199.
    Das S, Das DK. Anti-inflammatory responses of resveratrol. Inflamm Allergy Drug Targets. 2007;6(3):168–73.CrossRefPubMedGoogle Scholar
  200. 200.
    Holmes-McNary M, Baldwin AS. Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IκB kinase. Cancer Res. 2000;60(13):3477–83.PubMedGoogle Scholar
  201. 201.
    Jiang Z, et al. Toll-like receptor 3-mediated activation of NF-κB and IRF3 diverges at toll-IL-1 receptor domain-containing adapter inducing IFN-β. Proc Natl Acad Sci. 2004;101(10):3533–8.CrossRefPubMedGoogle Scholar
  202. 202.
    Youn HS, et al. Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: molecular targets are TBK1 and RIP1 in TRIF complex. J Immunol. 2005;175(5):3339–46.CrossRefPubMedGoogle Scholar
  203. 203.
    Kundu JK, et al. Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-κB in mouse skin by blocking IκB kinase activity. Carcinogenesis. 2006;27(7):1465–74.CrossRefPubMedGoogle Scholar
  204. 204.
    Bar-Sela G, Epelbaum R, Schaffer M. Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr Med Chem. 2010;17(3):190–7.CrossRefPubMedGoogle Scholar
  205. 205.
    Mills, S. and K. Bone, Principles and practice of phytotherapy. Modern herbal medicine 2000: Churchill Livingstone.Google Scholar
  206. 206.
    Holt PR, Katz S, Kirshoff R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci. 2005;50(11):2191–3.CrossRefPubMedGoogle Scholar
  207. 207.
    Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23(1/A):363–98.PubMedGoogle Scholar
  208. 208.
    Liu Z, et al. Curcumin upregulates Nrf2 nuclear translocation and protects rat hepatic stellate cells against oxidative stress. Mol Med Rep. 2016;13(2):1717–24.CrossRefPubMedGoogle Scholar
  209. 209.
    Biswas SK, et al. Curcumin induces glutathione biosynthesis and inhibits NF-κB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity. Antioxid Redox Signal. 2005;7(1–2):32–41.CrossRefPubMedGoogle Scholar
  210. 210.
    Jin CY, et al. Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia 1. Acta Pharmacol Sin. 2007;28(10):1645–51.CrossRefPubMedGoogle Scholar
  211. 211.
    Ak T, Gülçin İ. Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact. 2008;174(1):27–37.CrossRefPubMedGoogle Scholar
  212. 212.
    ABE Y, Hashimoto S, HORIE T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res. 1999;39(1):41–7.CrossRefPubMedGoogle Scholar
  213. 213.
    Ghanaatian N, et al. Curcumin as a therapeutic candidate for multiple sclerosis: molecular mechanisms and targets. J Cell Physiol. 2018.Google Scholar
  214. 214.
    Chan MM-Y. Inhibition of tumor necrosis factor by curcumin, a phytochemical. Biochem Pharmacol. 1995;49(11):1551–6.CrossRefPubMedGoogle Scholar
  215. 215.
    Banerjee M, et al. Modulation of inflammatory mediators by ibuprofen and curcumin treatment during chronic inflammation in rat. Immunopharmacol Immunotoxicol. 2003;25(2):213–24.CrossRefPubMedGoogle Scholar
  216. 216.
    Gukovsky I, et al. Curcumin ameliorates ethanol and nonethanol experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2003;284(1):G85–95.CrossRefPubMedGoogle Scholar
  217. 217.
    Kaur G, et al. Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents. Clin Exp Immunol. 2006;145(2):313–21.CrossRefPubMedPubMedCentralGoogle Scholar
  218. 218.
    Heitkemper MM, et al. Symptoms across the menstrual cycle in women with irritable bowel syndrome. Am J Gastroenterol. 2003;98(2):420.CrossRefPubMedGoogle Scholar
  219. 219.
    Smith YR, et al. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J Neurosci. 2006;26(21):5777–85.CrossRefPubMedPubMedCentralGoogle Scholar
  220. 220.
    Braniste V, et al. Oestradiol decreases colonic permeability through oestrogen receptor β-mediated up-regulation of occludin and junctional adhesion molecule-a in epithelial cells. J Physiol. 2009;587(13):3317–28.CrossRefPubMedPubMedCentralGoogle Scholar
  221. 221.
    Morito K, et al. Interaction of phytoestrogens with estrogen receptors α and β. Biol Pharm Bull. 2001;24(4):351–6.CrossRefPubMedGoogle Scholar
  222. 222.
    Seo HS, et al. Phytoestrogens induce apoptosis via extrinsic pathway, inhibiting nuclear factor-κB signaling in HER2-overexpressing breast cancer cells. Anticancer Res. 2011;31(10):3301–13.PubMedGoogle Scholar
  223. 223.
    Li Z, et al. Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen-activated protein kinase pathway. Toxicol in Vitro. 2008;22(7):1749–53.CrossRefPubMedGoogle Scholar
  224. 224.
    Pan H, et al. Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway. Int J Mol Med. 2012;30(2):337–43.CrossRefPubMedGoogle Scholar
  225. 225.
    Polivka J Jr. And F. Janku, Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther. 2014;142(2):164–75.CrossRefPubMedGoogle Scholar
  226. 226.
    Gil EMC. Targeting the PI3K/AKT/mTOR pathway in estrogen receptor-positive breast cancer. Cancer Treat Rev. 2014;40(7):862–71.CrossRefGoogle Scholar
  227. 227.
    Chen J, et al. Genistein induces apoptosis by the inactivation of the IGF-1R/p-Akt signaling pathway in MCF-7 human breast cancer cells. Food Funct. 2015;6(3):995–1000.CrossRefPubMedGoogle Scholar
  228. 228.
    Ahmad A, et al. Deregulation of PI3K/Akt/mTOR signaling pathways by isoflavones and its implication in cancer treatment. Anti Cancer Agents Med Chem. 2013;13(7):1014–24.CrossRefGoogle Scholar
  229. 229.
    Huang X, et al. Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma. Am J Pathol. 2012;181(1):26–33.CrossRefPubMedPubMedCentralGoogle Scholar
  230. 230.
    Shim H-Y, et al. Genistein-induced apoptosis of human breast cancer MCF-7 cells involves calpain–caspase and apoptosis signaling kinase 1–p38 mitogen-activated protein kinase activation cascades. Anti-Cancer Drugs. 2007;18(6):649–57.CrossRefPubMedGoogle Scholar
  231. 231.
    Liu H, et al. Delayed activation of extracellular-signal-regulated kinase 1/2 is involved in genistein-and equol-induced cell proliferation and estrogen-receptor-α-mediated transcription in MCF-7 breast cancer cells. J Nutr Biochem. 2010;21(5):390–6.CrossRefPubMedGoogle Scholar
  232. 232.
    Yang X, et al. Genistein induces enhanced growth promotion in ER-positive/erbB-2-overexpressing breast cancers by ER–erbB-2 cross talk and p27/kip1 downregulation. Carcinogenesis. 2010;31(4):695–702.CrossRefPubMedGoogle Scholar
  233. 233.
    Uifălean A, et al. Soy isoflavones and breast cancer cell lines: molecular mechanisms and future perspectives. Molecules. 2015;21(1):13.CrossRefPubMedCentralGoogle Scholar
  234. 234.
    Mencalha A, et al. Mapping oxidative changes in breast cancer: understanding the basic to reach the clinics. Anticancer Res. 2014;34(3):1127–40.PubMedGoogle Scholar
  235. 235.
    Sastre-Serra J, et al. Estrogen down-regulates uncoupling proteins and increases oxidative stress in breast cancer. Free Radic Biol Med. 2010;48(4):506–12.CrossRefPubMedGoogle Scholar
  236. 236.
    Pons DG, et al. Genistein modulates proliferation and mitochondrial functionality in breast cancer cells depending on ERalpha/ERbeta ratio. J Cell Biochem. 2014;115(5):949–58.CrossRefPubMedGoogle Scholar
  237. 237.
    Nadal-Serrano M, et al. The ERalpha/ERbeta ratio determines oxidative stress in breast cancer cell lines in response to 17Beta-estradiol. J Cell Biochem. 2012;113(10):3178–85.CrossRefPubMedGoogle Scholar
  238. 238.
    Prietsch R, et al. Genistein induces apoptosis and autophagy in human breast MCF-7 cells by modulating the expression of proapoptotic factors and oxidative stress enzymes. Mol Cell Biochem. 2014;390(1–2):235–42.CrossRefPubMedGoogle Scholar
  239. 239.
    Ullah MF, et al. Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species. Mol Nutr Food Res. 2011;55(4):553–9.CrossRefPubMedGoogle Scholar
  240. 240.
    Leung HY, et al. Genistein protects against polycyclic aromatic hydrocarbon-induced oxidative DNA damage in non-cancerous breast cells MCF-10A. Br J Nutr. 2008;101(2):257–62.CrossRefPubMedGoogle Scholar
  241. 241.
    Choi JN, et al. 2′-hydroxylation of genistein enhanced antioxidant and antiproliferative activities in mcf-7 human breast cancer cells. J Microbiol Biotechnol. 2009;19(11):1348–54.PubMedGoogle Scholar
  242. 242.
    Lee Y-M, et al. Dietary anthocyanins against obesity and inflammation. Nutrients. 2017;9(10):1089.CrossRefPubMedCentralGoogle Scholar
  243. 243.
    Neyrinck AM, et al. Polyphenol-rich extract of pomegranate peel alleviates tissue inflammation and hypercholesterolaemia in high-fat diet-induced obese mice: potential implication of the gut microbiota. Br J Nutr. 2013;109(5):802–9.CrossRefPubMedGoogle Scholar
  244. 244.
    Lu Y-C, Yeh W-C, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008;42(2):145–51.CrossRefPubMedGoogle Scholar
  245. 245.
    Moreira APB, et al. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr. 2012;108(5):801–9.CrossRefPubMedGoogle Scholar
  246. 246.
    Takeda, K. and S. Akira. TLR signaling pathways. In Seminars in immunology. 2004. Elsevier.Google Scholar
  247. 247.
    Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783–801.CrossRefPubMedGoogle Scholar
  248. 248.
    Kumar H, Kawai T, Akira S. Toll-like receptors and innate immunity. Biochem Biophys Res Commun. 2009;388(4):621–5.CrossRefPubMedGoogle Scholar
  249. 249.
    Rodes L, et al. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. J Microbiol Biotechnol. 2013;23(4):518–26.CrossRefPubMedGoogle Scholar
  250. 250.
    Villena J, Kitazawa H. Modulation of intestinal TLR4-inflammatory signaling pathways by probiotic microorganisms: lessons learned from Lactobacillus jensenii TL2937. Front Immunol. 2014;4:512.CrossRefPubMedPubMedCentralGoogle Scholar
  251. 251.
    Li Y, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167.CrossRefPubMedPubMedCentralGoogle Scholar
  252. 252.
    Zhang X-J, et al. Analgesic effect of paeoniflorin in rats with neonatal maternal separation-induced visceral hyperalgesia is mediated through adenosine A1 receptor by inhibiting the extracellular signal-regulated protein kinase (ERK) pathway. Pharmacol Biochem Behav. 2009;94(1):88–97.CrossRefPubMedGoogle Scholar
  253. 253.
    Liu, L., et al., The pharmacodynamic study on the effects of antinociception and anti-inflammation of the extracts of Fagopyrum cymosum (Trev.) Meisn. Med Inf, 2012. 25(49): p. 0.Google Scholar
  254. 254.
    Qin H-Y, et al. Quercetin attenuates visceral hypersensitivity and 5-Hydroxytryptamine availability in Postinflammatory irritable bowel syndrome rats: role of Enterochromaffin cells in the Colon. J Med Food. 2019;0(0):1–9.Google Scholar
  255. 255.
    Qu L, et al. Quercetin alleviates high glucose-induced Schwann cell damage by autophagy. Neural Regen Res. 2014;9(12):1195.CrossRefPubMedPubMedCentralGoogle Scholar
  256. 256.
    Hanasaki Y, Ogawa S, Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med. 1994;16(6):845–50.CrossRefPubMedGoogle Scholar
  257. 257.
    Cushnie TT, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents. 2005;26(5):343–56.CrossRefPubMedGoogle Scholar
  258. 258.
    Vanacker SA, et al. Flavonoids as scavengers of nitric oxide radical. Biochem Biophys Res Commun. 1995;214(3):755–9.CrossRefGoogle Scholar
  259. 259.
    Heijnen CG, et al. Peroxynitrite scavenging of flavonoids: structure activity relationship. Environ Toxicol Pharmacol. 2001;10(4):199–206.CrossRefPubMedGoogle Scholar
  260. 260.
    Ghosh B. Quercetin inhibits LPS-induced nitric oxide and tumor necrosis factor-α production in murine macrophages. Int J Immunopharmacol. 1999;21(7):435–43.CrossRefPubMedGoogle Scholar
  261. 261.
    Gerster R, et al. Anti-inflammatory function of high-density lipoproteins via autophagy of IkappaB kinase. Cell Mol Gastroenterol Hepatol. 2015;1(2):171–87 e1.CrossRefPubMedGoogle Scholar
  262. 262.
    Bureau G, Longpré F, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res. 2008;86(2):403–10.CrossRefPubMedGoogle Scholar
  263. 263.
    Nair MP, et al. The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-κβ system. Clin Vaccine Immunol. 2006;13(3):319–28.CrossRefPubMedPubMedCentralGoogle Scholar
  264. 264.
    Cho S-Y, et al. Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-κB pathway in lipopolysaccharide-stimulated macrophage. Mol Cell Biochem. 2003;243(1–2):153–60.CrossRefPubMedGoogle Scholar
  265. 265.
    Kempuraj D, et al. Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br J Pharmacol. 2005;145(7):934–44.CrossRefPubMedPubMedCentralGoogle Scholar
  266. 266.
    Kobuchi H, et al. Ginkgo biloba extract (EGb 761): inhibitory effect on nitric oxide production in the macrophage cell line RAW 264.7. Biochem Pharmacol. 1997;53(6):897–903.CrossRefPubMedGoogle Scholar
  267. 267.
    Zhou Y, et al. Natural polyphenols for prevention and treatment of cancer. Nutrients. 2016;8(8):515.Google Scholar
  268. 268.
    Gormaz JG, et al. Potential role of polyphenols in the prevention of cardiovascular diseases: molecular bases. Curr Med Chem. 2016;23(2):115–28.Google Scholar
  269. 269.
    Bahadoran Z, Mirmiran P, Azizi F. Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. J Diabetes Metab Disord. 2013;12(1):43.CrossRefPubMedPubMedCentralGoogle Scholar
  270. 270.
    Karunaweera N, et al. Plant polyphenols as inhibitors of NF-κB induced cytokine production—a potential anti-inflammatory treatment for Alzheimer's disease? Front Mol Neurosci. 2015;8:24.CrossRefPubMedPubMedCentralGoogle Scholar
  271. 271.
    Martin DA, Bolling BW. A review of the efficacy of dietary polyphenols in experimental models of inflammatory bowel diseases. Food Funct. 2015;6(6):1773–86.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Nazanin Momeni Roudsari
    • 1
  • Naser-Aldin Lashgari
    • 1
  • Saeideh Momtaz
    • 2
    • 3
    • 4
  • Mohammad Hosein Farzaei
    • 5
    • 6
    Email author
  • André M. Marques
    • 7
  • Amir Hossein Abdolghaffari
    • 1
    • 2
    • 3
    • 4
    • 8
    Email author
  1. 1.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences BranchIslamic Azad UniversityTehranIran
  2. 2.Medicinal Plants Research CenterInstitute of Medicinal Plants, ACECRKarajIran
  3. 3.Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS)Tehran University of Medical SciencesTehranIran
  4. 4.Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran
  5. 5.Pharmaceutical Sciences Research Center, Health InstituteKermanshah University of Medical SciencesKermanshahIran
  6. 6.Medical Biology Research CenterKermanshah University of Medical SciencesKermanshahIran
  7. 7.Oswaldo Cruz Foundation (FIOCRUZ)Institute of Technology in Pharmaceuticals (Farmanguinhos)Rio de JaneiroBrazil
  8. 8.Gastrointestinal Pharmacology Interest Group (GPIG)Universal Scientific Education and Research Network (USERN)TehranIran

Personalised recommendations