Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Food Chem Toxicol. 2020 Nov;145:111680. doi: 10.1016/j.fct.2020.111680. Epub 2020 Aug 9.
Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence worldwide. Currently used treatments of UC are unsatisfactory, while natural bioactive compounds are considered to be emerging therapeutic agents. Luteolin (Lut) is a natural compound with beneficial effects in a variety of diseases, however, its effect in UC has been poorly studied. In this study we investigated the effect of Lut in posttreatment and cotreatment of dextran sulfate sodium (DSS)-induced experimental colitis in mice. In addition, the role of extracellular signal-regulated kinases 1/2 (ERK1/2) in the mechanism of action of Lut in experimental colitis was investigated using the ERK inhibitor PD0325901. Lut attenuated symptoms of DSS-induced colitis in mice, ameliorated colon tissue damage and reduced inflammation, apoptosis and autophagy. The effect was more pronounced if Lut was administered simultaneously with DSS. The administration of ERK inhibitor exacerbated DSS-induced colitis symptoms and prevented the protective effects of Lut. The results provide new mechanistic details underlying the anti-inflammatory, anti-apoptotic and anti-autophagic effects of Lut through the activation of the ERK signaling pathway. This suggested that Lut can be used as a novel therapeutic candidate in the treatment of UC or could be used as a supplement to existing therapy.
溃疡性结肠炎（UC）是一种全球范围内发病率和患病率不断增加的慢性炎症性疾病。目前用于治疗 UC 的方法并不令人满意，而天然生物活性化合物被认为是新兴的治疗药物。木樨草素（Lut）是一种具有多种疾病有益作用的天然化合物，但其在 UC 中的作用研究甚少。在这项研究中，我们研究了木樨草素在葡聚糖硫酸钠（DSS）诱导的实验性结肠炎小鼠的后治疗和共同治疗中的作用。此外，使用 ERK 抑制剂 PD0325901 研究了 ERK1/2 在木樨草素在实验性结肠炎中的作用机制中的作用。木樨草素可减轻 DSS 诱导的结肠炎小鼠的症状，改善结肠组织损伤并减轻炎症、细胞凋亡和自噬。如果木樨草素与 DSS 同时给药，效果更为明显。ERK 抑制剂的给药加剧了 DSS 诱导的结肠炎症状，并阻止了木樨草素的保护作用。这些结果提供了木樨草素通过激活 ERK 信号通路发挥抗炎、抗细胞凋亡和抗自噬作用的新的机制细节。这表明木樨草素可用作治疗 UC 的新型治疗候选药物，或可作为现有治疗方法的补充。
