School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, P.R. China.
Yu-Huang-Ding Hospital/ Qingdao University, 264000 Yantai, Shandong, P.R. China.
Int Immunopharmacol. 2018 Apr;57:82-90. doi: 10.1016/j.intimp.2018.02.012. Epub 2018 Feb 22.
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD), which is characterized by chronic intestinal inflammation and leads to an increased risk of colon cancer. There are many studies using phyto-ingredients as a novel approach for the treatment of UC. The plant Andrographis paniculata (Acanthaceae) is a safe and edible vegetable that has been extensively adopted in traditional Chinese medicine for conditions involving inflammation, and the most active phytochemical agent is andrographolide. The andrographolide derivative 3,14,19-triacetyl andrographolide, which is known as CX-10 (a hemi chemical synthesized from andrographolide), has been found to possess strong anti-inflammatory properties. In the present study, we investigated the therapeutic potential of CX-10 as a complementary and alternative medicine against dextran sulphate sodium (DSS)-induced ulcerative colitis in mice. Our results revealed that CX-10 treatment reduced body weight loss, reduced colon length shortening, decreased colon weight, decreased the spleen index, decreased the disease activity index (DAI), and alleviated histological damage in the colon. The expression of TNF-α and IL-6 and the activity of myeloperoxidase (MPO) in colonic tissues were significantly reduced in CX-10 supplemented mice. It is noteworthy that the efficacy of 200 mg/kg of CX-10 was equivalent to that of the mesalazine positive control (200 mg/kg). Furthermore, western blot analysis revealed that CX-10 treatment reduced the expression of nuclear factor-κB (NF-κB) p65 and p-IκBα, increased the expression of IκBα and down-regulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK), ERK and JNK. In conclusion, CX-10 treatment attenuated DSS-induced UC in mice through inhibiting the activation of NF-κB and MAPK pathways and reducing TNF-α and IL-6 levels, suggesting that CX-10 is a potential therapeutic drug for UC.
溃疡性结肠炎（UC）是一种炎症性肠病（IBD），其特征为慢性肠道炎症，并导致结肠癌风险增加。有许多研究使用植物成分作为治疗 UC 的新方法。穿心莲（爵床科）是一种安全可食用的蔬菜，在传统中药中广泛用于炎症相关疾病，最活跃的植物化学物质是穿心莲内酯。穿心莲内酯衍生物 3,14,19-三乙酰穿心莲内酯，又称 CX-10（从穿心莲内酯半化学合成），已被发现具有很强的抗炎特性。在本研究中，我们研究了 CX-10 作为一种补充和替代药物治疗葡聚糖硫酸钠（DSS）诱导的小鼠溃疡性结肠炎的治疗潜力。我们的结果表明，CX-10 治疗可减少体重减轻、结肠缩短、结肠重量减轻、脾脏指数降低、疾病活动指数（DAI）降低和结肠组织学损伤减轻。CX-10 补充的小鼠结肠组织中 TNF-α 和 IL-6 的表达以及髓过氧化物酶（MPO）的活性明显降低。值得注意的是，200mg/kg 的 CX-10 的疗效与美沙拉嗪阳性对照（200mg/kg）相当。此外，Western blot 分析表明，CX-10 治疗可降低核因子-κB（NF-κB）p65 和 p-IκBα 的表达，增加 IκBα 的表达，并下调 p38 丝裂原活化蛋白激酶（MAPK）、ERK 和 JNK 的磷酸化。总之，CX-10 通过抑制 NF-κB 和 MAPK 通路的激活以及降低 TNF-α 和 IL-6 水平来减轻 DSS 诱导的 UC 小鼠的病情，表明 CX-10 是一种潜在的 UC 治疗药物。
