Zhou Anfu, Zhang Shuqing, Yang Chengliang, Liao Nansheng, Zhang Yan
Department of Gastroenterology, The First Affiliated Hospital of Hainan Medical University, Haikou, China.
Department of Clinical Laboratory, The Second People's Hospital of Nantong, China.
Adv Clin Exp Med. 2022 May;31(5):529-538. doi: 10.17219/acem/146234.
Dextran sodium sulfate (DSS)-triggered ulcerative colitis (UC) model in animals provides a valuable platform to preclinically evaluate the outcome of drug candidates for UC. Dandelion root extracts (DRE) have a therapeutic effect on UC. However, the protective mechanism of DRE against UC remains unknown.
To discover the targeting pathway involved in DRE-induced protection against UC.
The UC model was developed in C57BL/6 mice by oral administration of DSS. Following DSS exposure, sulfasalazine (SASP), low dose of DRE (DRE-L), moderate dose of DRE (DRE-M), high dose of DRE (DRE-H), and DRE-H plus mitogen-activated protein kinases (MAPK) agonist (DRE-H+MA) were administered to the mice. Colon Mucosal Damage Index (CMDI) and histopathological analysis were used to evaluate the colonic mucosal damage. The cytokine levels were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. The MAPK pathway activation was determined with western blotting.
We found that DRE-H attenuated DSS-triggered colonic mucosal damage. The DSS-induced inflammatory responses and oxidative stress in the bloodstream and colon tissues were dramatically inhibited by DRE-H administration. Also, this plant impaired DSS-provoked phosphorylation levels of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), p38 mitogen-activated protein kinases (p38), p65, and IκB. More importantly, MAPK agonist, BIM-23A760, removed the protective effect of DRE-H on the bloodstream and colon tissues.
The DRE-H is capable of relieving DSS-induced UC, and its mechanism links to the MAPK pathways.
葡聚糖硫酸钠（DSS）诱导的动物溃疡性结肠炎（UC）模型为临床前评估UC候选药物的疗效提供了一个有价值的平台。蒲公英根提取物（DRE）对UC具有治疗作用。然而，DRE对UC的保护机制尚不清楚。
发现DRE诱导的对UC保护作用所涉及的靶向途径。
通过口服给予DSS在C57BL/6小鼠中建立UC模型。在暴露于DSS后，给小鼠施用柳氮磺胺吡啶（SASP）、低剂量DRE（DRE-L）、中剂量DRE（DRE-M）、高剂量DRE（DRE-H）以及DRE-H加丝裂原活化蛋白激酶（MAPK）激动剂（DRE-H+MA）。采用结肠黏膜损伤指数（CMDI）和组织病理学分析评估结肠黏膜损伤。使用商业酶联免疫吸附测定（ELISA）试剂盒检测细胞因子水平。通过蛋白质印迹法测定MAPK途径的激活情况。
我们发现DRE-H减轻了DSS引发的结肠黏膜损伤。给予DRE-H可显著抑制DSS诱导的血液和结肠组织中的炎症反应及氧化应激。此外，这种植物削弱了DSS引起的细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）、p38丝裂原活化蛋白激酶（p38）、p65和IκB的磷酸化水平。更重要的是，MAPK激动剂BIM-23A760消除了DRE-H对血液和结肠组织的保护作用。
DRE-H能够缓解DSS诱导的UC，其机制与MAPK途径有关。
