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Luteolin ameliorates experimental colitis in mice through ERK-mediated suppression of inflammation, apoptosis and autophagy

Ulcerative colitis (UC) is one of the major forms of inflammatory bowel disease with an increasing incidence and prevalence worldwide. It is a chronic remitting and relapsing disease that occurs spontaneously characterized by gastrointestinal symptoms, and significantly affects the quality of life1. Currently used treatments for UC are unsatisfactory due to various side effects, failure in the induction of remission and prevention of relapse, as well as high economic costs2. Recently, the use of natural compounds has become increasingly attractive in the prevention and treatment of various diseases, including UC. Luteolin (3′, 4′, 5, 7- tetrahydroxyflavone ; Lut) is a common flavonoid present in many edible plants that has been shown to have beneficial effects on various diseases3, however, its effect on UC has been poorly studied. In this study, we investigated the effect of Lut in the posttreatment and cotreatment of experimental colitis induced by dextran sulfate sodium (DSS) in mice. Lut attenuated clinical symptoms of DSS-induced colitis in mice by diminishing body weight loss and improving disease activity index, alleviated colon tissue damage, and reduced inflammation, apoptosis and autophagy. This effect was more pronounced when Lut was applied simultaneously with DSS. Additionally, the role of extracellular signal-regulated kinases 1/2 (ERK1/2) in the mechanism of action of Lut in experimental colitis was investigated as it was shown that Lut increased the activity of ERK1/2. Inhibition of ERK1/2 exacerbated the symptoms of DSS-induced colitis and diminished the protective effects of Lut as evidenced by worsening of inflammation and increased apoptosis and autophagy. Overall, the results of this study contributed to the elucidation of the underlying mechanism of action of Lut in experimental colitis and provided new mechanistic details underlying the antiinflammatory, antiapoptotic and antiautophagic effects of Lut through the activation of the ERK signaling pathway. In conclusion, the results suggest that Lut could be an effective therapeutic candidate for the treatment of UC, or a supplement to conventional therapy, although further clinical studies are required.

Ulcerative colitis, Luteolin, MAPK, ERK inhibitor, Inflammation, Apoptosis, Autophagy

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