Luteolin Ameliorates Dextran Sulfate Sodium-induced Colitis In Mice

Objective Luteolin has a reputation for being a safe and effective natural antioxidant and can be isolated from various plants worldwide,such as chinese starjasmine stem,wild chrysanthemum flower,honeysuckle,garden balsam stem and ajuga decumbens thunb,which exhibits a wide range of biological activities including anti-inflammatory,antibacterial,antioxidant,anticancer,and cytoprotective properties.Recently,the role of oxidative stress in ulcerative colitis(UC)has been well established and is increasingly highlighted.Thus,we studied the protective effect of luteolin administration in a mouse model of experimental colitis in order to provide a new method for clinical prevention and control of UC.Methods Experimental acute colitis was induced by administering 3%dextran sulfate sodium(DSS)in the drinking water of mice for 7 days.C57BL/6 mice were randomly divided into 5 groups:normal control group,the DSS model group and low-dose luteolin group(5 mg/kg),middle-dose luteolin group(20 mg/kg),high-dose luteolin group(50 mg/kg).The disease activity index(DAI);colon length;histological assessment;mRNA levels of tumor necrosis factor(TNF-a),interleukin-6(IL-6),nuclear factor-erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and NADP(H):quinone oxidoreductase 1(NQO-1);protein expression of Nrf2 were examined.Results Treatment with luteolin markedly attenuated the DAI compared with DSS model group(3.17±0.65?2.03±0.40?1.27±0.25 VS 3.90±0.36,P<0.05?P<0.01?P<0.01);Administration of luteolin ameliorated colon shortening on different levels(4.27±0.75?5.17±0.35?5.97±0.50 VS 3.67±0.65),medium?high-dose luteolin groups had significant difference in comparison with DSS model group(P<0.01);Histopathological analysis showed that luteolin effectively reduced histological alterations;RT-PCR results displayed that luteolin activated the expressions of Nrf2 and its downstream targets,including HO-1?NQO1 compared with DSS model group(0.18±0.08?0.16±0.13?0.19±0.10).Luteolin also significantly(P<0.05)reduced the level of TNF-??IL-6 in comparison with DSS model group(1.59±0.47?2.02±0.36).Western blot shown that compared with DSS model group,luteolin significantly(P<0.05)elevated the nuclear protein expression of Nrf2(0.13±0.62 VS 0.28±0.50?0.37±0.80?0.51±0.92).Conclusion Administration of luteolin has protective effect on experimental colitis,which can attenuate the DAI,colon shortening and histological damage.Maybe the mechanism is activating Nrf2 signaling pathway,promoting Nrf2 into nucleus and elevating mRNA levels of its downstream targets including HO-1 and NQOl suppressing mRNA expressions of TNF-??IL-6,thus enhancing colon antioxidant ability and regulating the oxidation/antioxidant balance.