Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Sep 14, 2013; 19(34): 5633-5644
Published online Sep 14, 2013. doi: 10.3748/wjg.v19.i34.5633
Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats
Salim S Al-Rejaie, Hatem M Abuohashish, Maher M Al-Enazi, Abdullah H Al-Assaf, Mihir Y Parmar, Mohammed M Ahmed
Salim S Al-Rejaie, Hatem M Abuohashish, Mihir Y Parmar, Mohammed M Ahmed, Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11544, Saudi Arabia
Maher M Al-Enazi, Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Salman bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
Abdullah H Al-Assaf, Department of Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11544, Saudi Arabia
Author contributions: Al-Rejaie SS, Abuohashish HM, Ahmed MM and Al-Assaf AH designed the research; Abuohashish HM, Parmar MY, Al-Assaf AH and Ahmed MM performed the research; Al-Rejaie SS, Abuohashish HM, Al-Enazi MM and Ahmed MM analyzed the data and wrote the paper.
Supported by The Deanship of Scientific Research at King Saud University for its funding this research through the research group project, No. RGP-VPP-266
Correspondence to: Salim S Al-Rejaie, Associate Professor of Pharmacology and Toxicology, Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO Box 55760, Riyadh 11544, Saudi Arabia. rejaie@ksu.edu.sa
Telephone: + 966-5-55992003 Fax: + 966-1-4679014
Received: February 6, 2013
Revised: June 9, 2013
Accepted: June 18, 2013
Published online: September 14, 2013
Processing time: 219 Days and 17.3 Hours
Abstract

AIM: To evaluate the ameliorative effect of naringenin (NG) during ulcerative colitis (UC) in rats.

METHODS: Rats were treated with three different doses (25, 50 and 100 mg/kg per day) of NG and a single dose of mesalazine (MES, 300 mg/kg per day) for seven days prior to ulcerative colitis induction by 4% acetic acid (AA). Twenty four hours after AA rectal administration, animals were scarified and the colonic tissues were dissected. Colonic mucus content was estimated using Alcian blue dye binding technique. In colon tissues, levels of total glutathione sulphadryls (T-GSH), non-protein sulphadryls (NP-SH) and thiobarbituric acid reactive substances (TBARS) were evaluated. The activities of the antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD) were measured. Concentrations of nucleic acids (DNA and RNA) and total protein were also estimated in colon tissues. Colonic levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and nitric oxide (NO) were estimated. In cross section of colitis tissue the histopathological changes were observed.

RESULTS: Colonic mucus content was decreased in AA compared to controls (587.09 ± 65.59 mg/kg vs 941.78 ± 68.41 mg/kg, P < 0.001). AA administration markedly reduced T-GSH (5.25 ± 0.37 nmol/L vs 3.04 ± 0.24 nmol/L, P < 0.01), NP-SH (3.16 ± 0.04 nmol/L vs 2.16 ± 0.30 nmol/L, P < 0.01), CAT (6.77 ± 0.40 U/mg vs 3.04 ± 0.2 U/mg, P < 0.01) and SOD (3.10 ± 0.11 U/mg vs 1.77 ± 0.18 U/mg, P < 0.01) while TBARS, TNF-α, IL-1β, IL-6, PGE2 and NO levels (15.09 ± 3.84 nmol/L vs 59.90 ± 16.34 nmol/L, P < 0.01; 113.56 ± 1.91 pg/mg vs 134.24 ± 4.77 pg/mg, P < 0.01; 209.20 ± 36.38 pg/mg vs 422.19 ± 31.47 pg/mg, P < 0.01; 250.83 ± 25.09 pg/mg vs 638.58 ± 115.9 pg/mg, P < 0.01; 248.19 ± 36.98 pg/mg vs 541.74 ± 58.34 pg/mg, P < 0.01 and 81.26 ± 2.98 mmol/g vs 101.90 ± 10.73 mmol/g, P < 0.001) were increased in colon of rats with UC compared controls respectively.Naringenin supplementation, significantly and dose dependently increased the colonic mucus content. The elevated TBARS levels were significantly decreased (39.35 ± 5.86 nmol/L, P < 0.05; 26.74 ± 3.17 nmol/L, P < 0.01 nmol/L and 17.74 ± 2.69 nmol/L, P < 0.01) compared to AA (59.90 ± 16.34 nmol/L) group while the decreased levels of T-GSH and NP-SH and activities of CAT and SOD found increased by NG treatments in dose dependent manner. The decreased values of nucleic acids and total protein in AA group were also significantly (P < 0.01) increased in all three NG supplemented groups respectively. NG pretreatment inhibited the TNF-α levels (123.76 ± 3.76 pg/mg, 122.62 ± 3.41 pg/mg and 121.51 ± 2.61 pg/mg vs 134.24 ± 4.78 pg/mg, P < 0.05) compared to AA group, respectively. Interleukins, IL-1β and IL-6 levels were also decreased in NG50 + AA (314.37 ± 16.31 pg/mg and 292.58 ± 23.68 pg/mg, P < 0.05) and NG100 + AA (416.72 ± 49.62 pg/mg and 407.96 ± 43.87 pg/mg, P < 0.05) when compared to AA (352.46 ± 8.58 pg/mg and 638.58 ± 115.98 pg/mg) group. Similar decrease (P < 0.05) was seen in PGE2 and NO values when compared to AA group. The group pretreated with MES, as a reference drug, showed significant (P < 0.01) protection against the changes induced in colon tissue by AA administration respectively.

CONCLUSION: In present study, NG produced antioxidant and anti-inflammatory effects demonstrating protective effect in inflammatory bowel disease.

Keywords: Naringenin; Ulcerative colitis; Inflammatory bowel disease; Oxidative stress

Core tip: Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), results in substantial morbidity and is difficult to treat. New strategies for adjunct therapies are needed. Systemic corticosteroids are highly effective at inducing clinical remission in cases of acute exacerbation of CD and UC; however, their use is limited by their frequent and sometimes severe side effects. Results of present study revealed that, naringenin has protective effects against acetic acid-induced UC by inhibiting inflammatory and oxidative bio-markers. Thus, it may pose promising outcomes for future clinical usage as a natural non-toxic effective supplement in IBD.