Objective: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) with common, repetitive inflammation of the colon and rectum, which is highly defined by loss of blood on colon mucosa, ulceration and acute inflammation. The present study aimed to investigate the potential protective effects of gallic acid (GA) through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model, using biochemical and histopathological parameters. Materials and Methods: The study consisted of four groups, each including seven rats, namely control group, colitis group, colitis-GA 50 mg/kg group and colitis-GA 100 mg/kg group. Colon tissue samples were analyzed for malondialdehyde (MDA), myeloperoxidase (MPO), cathepsin B and cathepsin L values. Results: Tissue MDA, MPO, cathepsin L and cathepsin B values increased significantly in colitis group (p=0.028, p=0.038, p=0.024, p=0.019, respectively). However, MDA, MPO, cathepsin L and cathepsin B values showed a significant decrease in animals with GA (at a dose of 100 mg/kg) administration in TNBS-induced colitis in rats (p=0.021, p=0.026, p=0.019, p=0.031, respectively). Colitis group was defined by the severe detriment of surface epithelium, submucosal edema and inflammatory cell infiltration. Treatment with GA significantly decreased inflammatory cell infiltration. Conclusion: GA can be used as an effective agent in the treatment of colitis due to its inhibitory properties in multiple pathways and its potent antioxidant effects.
1. Mi H, Liu FB, Li HW, Hou JT, Li PW. Anti-inflammatory effect of Chang-An-Shuan on TNBS-induced experimental colitis in rats. BMC Complement Altern Med 2017; 17(1): 315.
2. Bai X, Gou X, Cai P, Xu C, Cao L, Zhao Z, et al. Sesamin Enhances Nrf2-Mediated Protective Defense against Oxidative Stress and Inflammation in Colitis via AKT and ERK Activation. Oxid Med Cell Longev 2019; 2019: 2432416.
3. Jelsness-Jørgensen LP, Bernklev T, Henriksen M, Torp R, Moum BA. Chronic fatigue is more prevalent in patients with inflammatory bowel disease than in healthy controls. Inflamm Bowel Dis 2011; 17(7): 1564–72.
4. Teruel C, Garrido E, Mesonero F. Diagnosis and management of functional symptoms in inflammatory bowel disease in remission. World J Gastrointest Pharmacol Ther 2016; 7(1): 78–90.
5. Wang Z, Li S, Cao Y, Tian X, Zeng R, Liao DF, et al. Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer. Oxid Med Cell Longev 2016; 2016: 9875298.
6. Pereira C, Grácio D, Teixeira JP, Magro F. Oxidative Stress and DNA Damage: Implications in Inflammatory Bowel Disease. Inflamm Bowel Dis 2015; 21(10): 2403–17.
7. Aratani Y. Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function. Arch Biochem Biophys 2018; 640: 47–52. 8. Chapman AL, Mocatta TJ, Shiva S, Seidel A, Chen B, Khalilova I, et al. Ceruloplasmin is an endogenous inhibitor of myeloperoxidase. J Biol Chem 2013; 288(9): 6465–77.
9. Petushkova AI, Savvateeva LV, Korolev DO, Zamyatnin AA Jr. Cysteine Cathepsins: Potential Applications in Diagnostics and Therapy of Malignant Tumors. Biochemistry (Mosc) 2019; 84(7): 746–61.
10. Li YY, Fang J, Ao GZ. Cathepsin B and L inhibitors: a patent review (2010 - present). Expert Opin Ther Pat 2017; 27(6): 643–56.
11. Fernandes FH, Salgado HR. Gallic Acid: Review of the Methods of Determination and Quantification. Crit Rev Anal Chem 2016; 46(3): 257–65.
12. Choubey S, Varughese LR, Kumar V, Beniwal V. Medicinal importance of gallic acid and its ester derivatives: a patent review. Pharm Pat Anal 2015; 4(4): 305–15.
13. Kanbak G, Canbek M, Oğlakçı A, Kartkaya K, Sentürk H, Bayramoğlu G, et al. Preventive role of gallic acid on alcohol dependent and cysteine protease-mediated pancreas injury. Mol Biol Rep 2012; 39(12): 10249–55.
14. Cetinel S, Hancioğlu S, Sener E, Uner C, Kiliç M, Sener G, et al. Oxytocin treatment alleviates stress-aggravated colitis by a receptordependent mechanism. Regul Pept 2010; 160(1-3): 146–52.
15. Ernst O, Zor T. Linearization of the bradford protein assay. J Vis Exp 2010; (38): 1918.
16. Maiocchi SL, Morris JC, Rees MD, Thomas SR. Regulation of the nitric oxide oxidase activity of myeloperoxidase by pharmacological agents. Biochem Pharmacol 2017; 135: 90–115.
17. Tualeka AR, Martiana T, Ahsan A, Russeng SS, Meidikayanti W. Association between Malondialdehyde and Glutathione (L-gamma-Glutamyl-Cysteinyl-Glycine/GSH) Levels on Workers Exposed to Benzene in Indonesia. Open Access Maced J Med Sci 2019; 7(7): 1198–202.
18. Sairenji T, Collins KL, Evans DV. An Update on Inflammatory Bowel Disease. Prim Care 2017; 44(4): 673–92.
19. Bernstein CN. Assessing environmental risk factors affecting the inflammatory bowel diseases: a joint workshop of the Crohn’s & Colitis Foundations of Canada and the USA. Inflamm Bowel Dis 2008; 14(8): 1139–46.
20. Rana SV, Sharma S, Prasad KK, Sinha SK, Singh K. Role of oxidative stress & antioxidant defence in ulcerative colitis patients from north India. Indian J Med Res 2014; 139(4): 568–71.
21. Joo M, Kim HS, Kwon TH, Palikhe A, Zaw TS, Jeong JH, et al. Antiinflammatory Effects of Flavonoids on TNBS-induced Colitis of Rats. Korean J Physiol Pharmacol 2015; 19(1): 43–50.
22. Yildiz G, Yildiz Y, Ulutas PA, Yaylali A, Ural M. Resveratrol Pretreatment Ameliorates TNBS Colitis in Rats. Recent Pat Endocr Metab Immune Drug Discov 2015; 9(2): 134–40.
23. Lee IA, Hyun YJ, Kim DH. Berberine ameliorates TNBS-induced colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-κB activation. Eur J Pharmacol 2010; 648(1-3): 162–70.
24. Mancini S, Mariani F, Sena P, Benincasa M, Roncucci L. Myeloperoxidase expression in human colonic mucosa is related to systemic oxidative balance in healthy subjects. Redox Rep 2017; 22(6): 399–407.
25. Nauseef WM. Biosynthesis of human myeloperoxidase. Arch Biochem Biophys 2018; 642: 1–9.
26. Miroliaee AE, Esmaily H, Vaziri-Bami A, Baeeri M, Shahverdi AR, Abdollahi M. Amelioration of experimental colitis by a novel nanoselenium-silymarin mixture. Toxicol Mech Methods 2011; 21(3): 200–8.
27. Ghasemi-Pirbaluti M, Motaghi E, Najafi A, Hosseini MJ. The effect of theophylline on acetic acid induced ulcerative colitis in rats. Biomed Pharmacother 2017; 90: 153–9.
28. Pandurangan AK, Mohebali N, Norhaizan ME, Looi CY. Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice. Drug Des Devel Ther 2015; 9: 3923–34.
29. Gondi CS, Rao JS. Cathepsin B as a cancer target. Expert Opin Ther Targets 2013; 17(3): 281–91.
30. Vidak E, Javoršek U, Vizovišek M, Turk B. Cysteine Cathepsins and their Extracellular Roles: Shaping the Microenvironment. Cells 2019; 8(3): 264.