Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

General Research Article

Phloretin Ameliorates Acetic Acid Induced Colitis Through Modulation of Immune and Inflammatory Reactions in Rats

Author(s): Arya V.S. and Kanthlal S.K.*

Volume 21, Issue 1, 2021

Published on: 24 June, 2020

Page: [163 - 172] Pages: 10

DOI: 10.2174/1871530320666200624120257

Price: $65

Abstract

Background: Adverse effects associated with current therapy for Ulcerative colitis (UC) over prolonged treatment periods and the high relapse rate limit their use. Incorporating fruits as regular diet has beneficial role in the management of UC. Phloretin, a dihydrochalcone of apple is reported for its anti-oxidant and anti-inflammatory effects. Our study aims to evaluate the effectiveness of phloretin on experimentally induced ulcerative colitis in rats.

Methods: In vitro study was performed using Raw 264.7 cells stimulated with LPS (1μg/mL) and in in-vivo study, colitis was induced by intra rectal administration of 4% Acetic acid. Phloretin (50 mg/kg) was given orally for 3 days to Wistar rats after induction for the post-treatment group and 1 day before induction to the pre-treatment group. Macroscopical, biochemical and histopathological evaluations were performed to assess the effectiveness.

Results: A concentration dependent inhibition of MPO and iNOS activity was obtained in LPS stimulated neutrophil cells. Phloretin exerted ameliorative effect in both pre and post-treatment groups by restoring plasma ALP and LDH level and reduce inflammatory markers like myeloperoxidase, nitric oxide and eosinophil peroxidase level as well as downregulates colon ICAM-1 gene in acetic acid induced ulcerative colitis in rats. Antioxidative potency was confirmed by restoring tissue GSH level. Phloretin prevents mucosal damage and it was confirmed by histopathological analysis.

Conclusion: Collectively, our findings provide evidence that phloretin might be useful as a natural therapeutic agent in the management of UC as well as may pose a promising outcome for future clinical usage.

Keywords: Phloretin, ulcerative colitis, inflammation, ICAM, myeloperoxidase, nitric oxide.

Graphical Abstract
[1]
Luo, C-X.; Wen, Z-H.; Zhen, Y.; Wang, Z-J.; Mu, J-X.; Zhu, M.; Ouyang, Q.; Zhang, H. Chinese research into severe ulcerative colitis has increased in quantity and complexity. World J. Clin. Cases, 2018, 6(3), 35-43.
[http://dx.doi.org/10.12998/wjcc.v6.i3.35] [PMID: 29564356]
[2]
Ray, G. Inflammatory bowel disease in India - past, present and future. World J. Gastroenterol., 2016, 22(36), 8123-8136.
[http://dx.doi.org/10.3748/wjg.v22.i36.8123] [PMID: 27688654]
[3]
Peyrin-Biroulet, L.; Cieza, A.; Sandborn, W.J.; Coenen, M.; Chowers, Y.; Hibi, T.; Kostanjsek, N.; Stucki, G.; Colombel, J.F. Development of the first disability index for inflammatory bowel disease based on the international classification of functioning, disability and health. Gut, 2012, 61(2), 241-247.
[http://dx.doi.org/10.1136/gutjnl-2011-300049] [PMID: 21646246]
[4]
Niu, X.J.; Xu, J.Y.; Song, J.H. Biological therapies for inflammatory bowel diseases. World Chinese J Dig., 2013, 21, 3514-3519.
[http://dx.doi.org/10.11569/wcjd.v21.i32.3514]
[5]
Fok, K.C.; Ng, W.W.S.; Henderson, C.J.A.; Connor, S.J. Cutaneous sarcoidosis in a patient with ulcerative colitis on infliximab. J. Crohn’s Colitis, 2012, 6(6), 708-712. [Internet]
[http://dx.doi.org/10.1016/j.crohns.2012.01.008] [PMID: 22398084]
[6]
Ashok, K.; Mathew, A.A.; Thomas, A.; Mohan, D.; Gopalakrishna, R.; Reghu, R. Clinical pharmacist’s interventions on medication adherence and knowledge of inflammatory bowel disease patients. J. Young Pharm., 2017, 9, 381-385.
[http://dx.doi.org/10.5530/jyp.2017.9.76]
[7]
Limdi, J.K. Dietary practices and inflammatory bowel disease. Indian J. Gastroenterol., 2018, 37(4), 284-292.
[http://dx.doi.org/10.1007/s12664-018-0890-5] [PMID: 30209778]
[8]
Aliomrani, M.; Sepand, M.R.; Mirzaei, H.R.; Kazemi, A.R.; Nekonam, S.; Sabzevari, O. Effects of Phloretin on oxidative and inflammatory reaction in rat model of cecal ligation and puncture induced sepsis. Daru, 2016, 24(1), 15.
[http://dx.doi.org/10.1186/s40199-016-0154-9] [PMID: 27150961]
[9]
Salter, M.; Duffy, C.; Garthwaite, J.; Strijbos, P.J. Ex vivo measurement of brain tissue nitrite and nitrate accurately reflects nitric oxide synthase activity in vivo. J. Neurochem., 1996, 66(4), 1683-1690.
[http://dx.doi.org/10.1046/j.1471-4159.1996.66041683.x] [PMID: 8627326]
[10]
Cagin, Y.F.; Parlakpinar, H.; Vardi, N.; Polat, A.; Atayan, Y.; Erdogan, M.A.; Tanbek, K. Effects of dexpanthenol on acetic acidinduced colitis in rats. Exp. Ther. Med., 2016, 12(5), 2958-2964.
[http://dx.doi.org/10.3892/etm.2016.3728] [PMID: 27882101]
[11]
Dodda, D.; Chhajed, R.; Mishra, J. Protective effect of quercetin against acetic acid induced inflammatory bowel disease (IBD) like symptoms in rats: possible morphological and biochemical alterations. Pharmacol. Rep., 2014, 66(1), 169-173.
[http://dx.doi.org/10.1016/j.pharep.2013.08.013] [PMID: 24905324]
[12]
Ghasemi-Pirbaluti, M.; Motaghi, E.; Najafi, A.; Hosseini, M.J. The effect of theophylline on acetic acid induced ulcerative colitis in rats. Biomed. Pharmacother., 2017, 90, 153-159.
[http://dx.doi.org/10.1016/j.biopha.2017.03.038] [PMID: 28351778]
[13]
Vieira, ELM; Leonel, AJ; Sad, AP; Beltrão, NRM; Costa, TF; Ferreira, TMR Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis J Nutr Biochem. Elsevier Inc, 2012, 23, 430-436.
[14]
Montenegro, MF; Amaral, JH; Pinheiro, LC; Sakamoto, EK; Ferreira, GC; Reis, RI Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension Free Radic Biol Med. Elsevier Inc, 2011, 51, 144-152.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.04.005]
[15]
Mohammadi, M.T.; Amini, R.; Jahanbakhsh, Z.; Shekarforoush, S. Effects of atorvastatin on the hypertension-induced oxidative stress in the rat brain. Iran. Biomed. J., 2013, 17(3), 152-157.
[PMID: 23748894]
[16]
Algieri, F.; Rodriguez-Nogales, A.; Garrido-Mesa, N.; Zorrilla, P.; Burkard, N.; Pischel, I.; Sievers, H.; Benedek, B.; Feistel, B.; Walbroel, B.; Rodriguez-Cabezas, M.E.; Galvez, J. Intestinal anti-inflammatory activity of the Serpylli herba extract in experimental models of rodent colitis. J. Crohn’s Colitis, 2014, 8(8), 775-788.
[http://dx.doi.org/10.1016/j.crohns.2013.12.012]] [PMID: 24411672]
[17]
D’Argenio, G.; Mazzone, G.; Tuccillo, C.; Ribecco, M.T.; Graziani, G.; Gravina, A.G.; Caserta, S.; Guido, S.; Fogliano, V.; Caporaso, N.; Romano, M. Apple polyphenols extract (APE) improves colon damage in a rat model of colitis. Dig. Liver Dis., 2012, 44(7), 555-562.
[http://dx.doi.org/10.1016/j.dld.2012.01.009] [PMID: 22381211]
[18]
Hartmann, R.M.; Morgan Martins, M.I.; Tieppo, J.; Fillmann, H.S.; Marroni, N.P. Effect of Boswellia serrata on antioxidant status in an experimental model of colitis rats induced by acetic acid. Dig. Dis. Sci., 2012, 57(8), 2038-2044.
[http://dx.doi.org/10.1007/s10620-012-2134-3] [PMID: 22451119]
[19]
Ali, A.A.; Abd Al Haleem, E.N.; Khaleel, S.A.H.; Sallam, A.S. Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats. Pharmacol. Rep., 2017, 69(2), 268-275.
[http://dx.doi.org/10.1016/j.pharep.2016.11.002] [PMID: 28129600]
[20]
Popov, S.V.; Markov, P.A.; Nikitina, I.R.; Petrishev, S.; Smirnov, V.; Ovodov, Y.S. Preventive effect of a pectic polysaccharide of the common cranberry Vaccinium oxycoccos L. on acetic acid-induced colitis in mice. World J. Gastroenterol., 2006, 12(41), 6646-6651.
[http://dx.doi.org/10.3748/wjg.v12.i41.6646] [PMID: 17075978]
[21]
Chougule, N.B.; Nitve, S.A.; Koumaravelou, K. Phytochemical investigation and screening for inflammatory bowel disease activity of ethanolic extract of Kariyat. Pharmacogn. J., 2018, 10, 602-610.
[http://dx.doi.org/10.5530/pj.2018.3.99]
[22]
Leiman, D.A.; Lichtenstein, G.R. Therapy of inflammatory bowel disease: what to expect in the next decade. Curr. Opin. Gastroenterol., 2014, 30(4), 385-390.
[http://dx.doi.org/10.1097/MOG.0000000000000077] [PMID: 24902037]
[23]
Langmead, L.; Dawson, C.; Hawkins, C.; Banna, N.; Loo, S.; Rampton, D.S. Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease: an in vitro study. Aliment. Pharmacol. Ther., 2002, 16(2), 197-205.
[http://dx.doi.org/10.1046/j.1365-2036.2002.01157.x] [PMID: 11860402]
[24]
Thippeswamy, B.S.; Mahendran, S.; Biradar, M.I.; Pooja Raj, K.S.; Badami, S.; Veerapur, V.P. Protective effect of embelin against acetic acid induced ulcerative colitis in rats. Pharmacol Reports. Elsevier B.V., 2017, 69, 268-275.
[http://dx.doi.org/10.1016/j.ejphar.2010.12.012] [PMID: 21185828]
[25]
Vaiopoulou, A.; Gazouli, M.; Papadopoulou, A.; Anagnostopoulos, A.K.; Karamanolis, G.; Theodoropoulos, G.E.; M’Koma, A.; Tsangaris, G.T. Serum protein profiling of adults and children with Crohn disease. J. Pediatr. Gastroenterol. Nutr., 2015, 60(1), 42-47.
[http://dx.doi.org/10.1097/MPG.0000000000000579] [PMID: 25250685]
[26]
Mercier, S.; Breuillé, D.; Mosoni, L.; Obled, C.; Patureau Mirand, P. Chronic inflammation alters protein metabolism in several organs of adult rats. J. Nutr., 2002, 132(7), 1921-1928.http://www.ncbi.nlm.nih.gov/pubmed/12097671 [Internet]
[http://dx.doi.org/10.1093/jn/132.7.1921] [PMID: 12097671]
[27]
Schreiber, S.; Hämling, J.; Zehnter, E.; Howaldt, S.; Daerr, W.; Raedler, A.; Kruis, W. Renal tubular dysfunction in patients with inflammatory bowel disease treated with aminosalicylate. Gut, 1997, 40(6), 761-766.
[http://dx.doi.org/10.1136/gut.40.6.761] [PMID: 9245930]
[28]
Venkataranganna, M.V.; Rafiq, M.; Gopumadhavan, S.; Peer, G.; Babu, U.V.; Mitra, S.K. NCB-02 (standardized Curcumin preparation) protects dinitrochlorobenzene- induced colitis through down-regulation of NFkappa-B and iNOS. World J. Gastroenterol., 2007, 13(7), 1103-1107.
[http://dx.doi.org/10.3748/wjg.v13.i7.1103] [PMID: 17373747]
[29]
Grisham, M.B.; Pavlick, K.P.; Laroux, F.S.; Hoffman, J.; Bharwani, S.; Wolf, R.E. Nitric oxide and chronic gut inflammation: controversies in inflammatory bowel disease. J. Investig. Med., 2002, 50(4), 272-283.
[http://dx.doi.org/10.2310/6650.2002.33281] [PMID: 12109591]
[30]
Raygude, K.S.; Kandhare, A.D.; Ghosh, P.; Bodhankar, S.L. Anticonvulsant effect of fisetin by modulation of endogenous biomarkers. Biomed Prev Nutr. Elsevier Masson SAS, 2012, 2, 215-222.
[http://dx.doi.org/10.1016/j.bionut.2012.04.005]
[31]
Gosavi, T.P.; Kandhare, A.D.; Ghosh, P.; Bodhankar, S.L. Anticonvulsant activity of Argentum metallicum, a homeopathic preparation. Der Pharm Lett., 2012, 4, 626-637.
[32]
Halliwell, B.; Chirico, S. Lipid peroxidation: its mechanism, measurement, and significance. Am. J. Clin. Nutr., 1993, 57(5)(Suppl.), 715S-724S.
[http://dx.doi.org/10.1093/ajcn/57.5.715S] [PMID: 8475889]
[33]
Megha, K.J.; Babu, H.C. MV SK, Kanthlal SK. Polyphenol rich passion fruit inhibits Fenton’s reagent induced lipid peroxidation in rabbit colon. Int J Pharm Technol., 2016, 8, 25158-25163.
[34]
El-Beltagi, H.S.; Mohamed, H.I. Reactive oxygen species, lipid peroxidation and antioxidative defense mechanism. Not. Bot. Horti Agrobot. Cluj-Napoca, 2013, 41, 44-57.
[http://dx.doi.org/10.15835/nbha4118929]
[35]
Patil, M.V.; Bhise, S.; Kandhare, A. Pharmacological evaluation of ameliorative effect of aqueous extract of Cucumis sativus L. fruit formulation on wound healing in Wistar rats. Chronicles Young Sci., 2012, 2, 207.
[http://dx.doi.org/10.4103/2229-5186.93026]
[36]
Wedemeyer, J.; Vosskuhl, K. Role of gastrointestinal eosinophils in inflammatory bowel disease and intestinal tumours. Best Pract. Res. Clin. Gastroenterol., 2008, 22(3), 537-549.
[http://dx.doi.org/10.1016/j.bpg.2007.12.001] [PMID: 18492570]
[37]
Jawairia, M.; Shahzad, G.; Mustacchia, P. Eosinophilic gastrointestinal diseases: review and update. ISRN Gastroenterol., 2012.2012463689
[http://dx.doi.org/10.5402/2012/463689] [PMID: 22792476]
[38]
Lee, J-H.; Regmi, S.C.; Kim, J-A.; Cho, M.H.; Yun, H.; Lee, C-S.; Lee, J. Apple flavonoid phloretin inhibits Escherichia coli O157:H7 biofilm formation and ameliorates colon inflammation in rats. Infect. Immun., 2011, 79(12), 4819-4827.
[http://dx.doi.org/10.1128/IAI.05580-11] [PMID: 21930760]
[39]
Trzeciak-Jędrzejczyk, A.; Makosiej, R.; Kolejwa, M.; Głowacka, E.; Czkwianianc, E. The role of adhesion molecules in inflammatory bowel disease in children. Assessment of the possible risk of cardiovascular complications. Prz. Gastroenterol., 2017, 12(3), 181-185.
[http://dx.doi.org/10.5114/pg.2017.70480] [PMID: 29123578]
[40]
Reinisch, W.; Hung, K.; Hassan-Zahraee, M.; Cataldi, F. Targeting endothelial ligands: ICAM-1/alicaforsen, MAdCAM-1. J. Crohn’s Colitis, 2018, 12(suppl_2), S669-S677.
[http://dx.doi.org/10.1093/ecco-jcc/jjy059] [PMID: 29757363]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy