Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Int Immunopharmacol. 2020 Jul;84:106567. doi: 10.1016/j.intimp.2020.106567. Epub 2020 May 12.
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.
木香烃内酯（CTL）是广藿香中的主要倍半萜内酯，广泛用于治疗胃肠道疾病。然而，木香烃内酯在溃疡性结肠炎（UC）中的治疗效果尚不清楚。在此，我们旨在评估木香烃内酯对 UC 的治疗作用及其潜在机制。ICR 小鼠腹腔注射木香烃内酯（10mg/kg）10 天。从给药第 4 天开始，通过给予 4%葡聚糖硫酸钠（DSS）额外 7 天诱导急性结肠炎。木香烃内酯显著减轻 DSS 诱导的体重减轻、结肠缩短、疾病活动指数升高和结肠组织病理损伤，并减少结肠组织中 CD4 T 细胞的数量。此外，木香烃内酯还显著抑制 DSS 暴露小鼠结肠组织髓过氧化物酶（MPO）活性和一氧化氮（NO）水平。同时，木香烃内酯还抑制 DSS 诱导的诱导型一氧化氮合酶（iNOS）、白细胞介素-1β（IL-1β）、IL-6、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）在 mRNA 和蛋白水平的表达。机制上，木香烃内酯抑制核因子 kappa-B（NF-κB）p65 的磷酸化和 NF-κB 抑制剂（IκB）的降解，以及 DSS 挑战小鼠结肠组织中信号转导和转录激活因子 1/3（STAT1/3）和丝氨酸/苏氨酸蛋白激酶 Akt（Akt）的过度激活。这些发现成功地表明，木香烃内酯通过抑制 NF-κB、STAT1/3 和 Akt 通路的失活来改善 DSS 诱导的小鼠急性结肠炎。这些结果还表明，木香烃内酯可能是治疗急性 UC 的潜在治疗剂。
