Effect of luteolin on ulcerative colitis in mice

Abstract

Objective To investigate the effects of luteolin ondextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Methods Experimental acute colitis was induced by administering 3% DSS in the drinking water. 40 C57BL/6 mice were randomly divided into normal control group, DSS model group, low, medium, high-dose luteolin groups. The disease activity index (DAI), colon length, histological assessment, mRNA expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate (NADPH), quinone oxidoreductase 1 (NQO1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), 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=0.046, 0.000, 0.000); 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 luteolingroups had significant difference in comparison with DSS model group (P=0.003, 0.001); Histopathological analysis showed that luteolin effectively reduced histological alterations; reverse transcriptase-polymerase chain reaction (RT-PCR) displayed that luteolin activated the expression 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=0.005, 0.002, 0.001; P=0.002, 0.000, 0.000); reduced the levels of TNF-α, IL-6 in comparison with DSS model group (1.59±0.47, 2.02±0.36). Western blotting shown that compared with DSS model group, luteolin significantly elevated the nuclear protein expression of Nrf2 (0.13±0.62 vs. 0.28±0.50, 0.37±0.80, 0.51±0.92; P=0.026, 0.002, 0.000). Conclusion Administration of luteolin has protective effect on experimental colitis, maybe the mechanism is activating Nrf2 signaling pathway, promoting Nrf2 into nucleus and elevating mRNA levels of its downstream targets HO-1 and NQO1, suppressing mRNA expressions of TNF-α, IL-6, thus enhancing colon antioxidant ability and regulating the oxidation/antioxidant balance. Key words: Luteolin; Ulcerative colitis; Nuclear factor-erythroid 2-related factor 2