Costunolide improved dextran sulfate sodium-induced acute ulcerative colitis in mice through NF-κB, STAT1/3, and Akt signaling pathways

Costunolide (CTL) is the major sesquiterpene lactone from Radix Aucklandiae, which is widely used on the treatment of gastrointestinal diseases. However, the therapeutic effect of costunolide in ulcerative colitis (UC) is still unknown. Herein, we sought to evaluate the therapeutic effects and underlying mechanisms of costunolide on UC. ICR mice were intraperitoneally administered with costunolide (10 mg/kg) for 10 days. Beginning on the 4th day of drug administration, acute colitis was induced by feeding 4% dextran sulfate sodium (DSS) for additional 7 days. Costunolide markedly attenuated DSS-induced body weight loss, colonic shortening, elevation in disease activity index, and pathological damage of colon, and decreased the number of CD4+ T cells in colon tissues. Furthermore, costunolide significantly inhibited myeloperoxidase (MPO) activity and nitric oxide (NO) level in colon tissues in DSS-exposed mice. Meanwhile, costunolide also suppressed DSS-induced expression of induced nitric oxide synthase (iNOS), interleukin-1β (IL‐1β), IL‐6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in both mRNA and protein levels. Mechanistically, costunolide repressed the phosphorylation of nuclear factor kappa-B (NF-κB) p65 and degradation of inhibitor of NF-κB (IκB), as well as the excessive activation of signal transducers and activators of transcription 1/3 (STAT1/3) and serine/threonine protein kinase Akt (Akt) in colon tissues in DSS-challenged mice. These findings successfully demonstrated that costunolide ameliorated DSS-induced murine acute colitis by suppressing inflammation through inactivation of NF-κB, STAT1/3, and Akt pathways. These results also suggested that costunolide may be a potential therapeutic agent for the treatment of acute UC.