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.
World J Gastroenterol. 2013 Sep 14;19(34):5633-44. doi: 10.3748/wjg.v19.i34.5633.
To evaluate the ameliorative effect of naringenin (NG) during ulcerative colitis (UC) in rats.
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.
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.
In present study, NG produced antioxidant and anti-inflammatory effects demonstrating protective effect in inflammatory bowel disease.
评估柚皮素（NG）在溃疡性结肠炎（UC）大鼠中的改善作用。
大鼠分别用 25、50 和 100 mg/kg/天三个剂量的 NG 和 300 mg/kg/天单剂量美沙拉嗪（MES）预处理 7 天，然后用 4%乙酸（AA）诱导溃疡性结肠炎。AA 直肠给药后 24 小时，处死动物并分离结肠组织。用 Alcian 蓝染色结合法估计结肠粘蛋白含量。在结肠组织中，评估总谷胱甘肽巯基（T-GSH）、非蛋白巯基（NP-SH）和硫代巴比妥酸反应物质（TBARS）的水平。测定抗氧化酶，过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的活性。还估计了结肠组织中的核酸（DNA 和 RNA）和总蛋白的浓度。估计了结肠组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、前列腺素 E2（PGE2）和一氧化氮（NO）的水平。观察结肠炎组织切片的组织学变化。
与对照组（587.09 ± 65.59 mg/kg 对 941.78 ± 68.41 mg/kg，P < 0.001）相比，AA 给药显著降低了结肠粘蛋白含量。AA 给药明显降低了 T-GSH（5.25 ± 0.37 nmol/L 对 3.04 ± 0.24 nmol/L，P < 0.01）、NP-SH（3.16 ± 0.04 nmol/L 对 2.16 ± 0.30 nmol/L，P < 0.01）、CAT（6.77 ± 0.40 U/mg 对 3.04 ± 0.2 U/mg，P < 0.01）和 SOD（3.10 ± 0.11 U/mg 对 1.77 ± 0.18 U/mg，P < 0.01），而 TBARS、TNF-α、IL-1β、IL-6、PGE2 和 NO 水平（15.09 ± 3.84 nmol/L 对 59.90 ± 16.34 nmol/L，P < 0.01；113.56 ± 1.91 pg/mg 对 134.24 ± 4.77 pg/mg，P < 0.01；209.20 ± 36.38 pg/mg 对 422.19 ± 31.47 pg/mg，P < 0.01；250.83 ± 25.09 pg/mg 对 638.58 ± 115.9 pg/mg，P < 0.01；248.19 ± 36.98 pg/mg 对 541.74 ± 58.34 pg/mg，P < 0.01 和 81.26 ± 2.98 mmol/g 对 101.90 ± 10.73 mmol/g，P < 0.001）在 UC 大鼠结肠中升高。柚皮素补充剂显著且剂量依赖性地增加了结肠粘蛋白含量。TBARS 水平显著降低（39.35 ± 5.86 nmol/L，P < 0.05；26.74 ± 3.17 nmol/L，P < 0.01 和 17.74 ± 2.69 nmol/L，P < 0.01）与 AA（59.90 ± 16.34 nmol/L）组相比，而 NG 处理发现 T-GSH 和 NP-SH 水平降低，CAT 和 SOD 活性升高，呈剂量依赖性。AA 组中核酸和总蛋白的降低值也分别显著（P < 0.01）增加。NG 预处理抑制 TNF-α 水平（123.76 ± 3.76 pg/mg、122.62 ± 3.41 pg/mg 和 121.51 ± 2.61 pg/mg 对 134.24 ± 4.78 pg/mg，P < 0.05）与 AA 组相比，分别。白细胞介素 IL-1β 和 IL-6 水平也在 NG50 + AA（314.37 ± 16.31 pg/mg 和 292.58 ± 23.68 pg/mg，P < 0.05）和 NG100 + AA（416.72 ± 49.62 pg/mg 和 407.96 ± 43.87 pg/mg，P < 0.05）与 AA（352.46 ± 8.58 pg/mg 和 638.58 ± 115.98 pg/mg）组相比降低。与 AA 组相比，PGE2 和 NO 值也出现类似降低（P < 0.05）。作为参考药物的 MES 预处理组分别显示出对 AA 给药引起的结肠组织变化的显著（P < 0.01）保护作用。
在本研究中，NG 产生抗氧化和抗炎作用，在炎症性肠病中显示出保护作用。
