Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou 510632, China.
Sci Rep. 2016 Jul 20;6:29716. doi: 10.1038/srep29716.
Andrographolide is a traditional herb medicine, widely used in Asia for conditions involving inflammation. The andrographlide-lipoic acid conjugate, AL-1, has been found being able to alleviate inflammation in our previous reports. Although the anti-inflammatory activity of AL-1 contributes to its cytoprotective effects, whether AL-1 can improve inflammatory bowel disease (IBD) and the underlying mechanisms of its action remain largely unknown. In this study, we investigated the anti-inflammatory effects of AL-1 in C57BL/6 mice with trinitrobenzenesulfonic acid (TNBS)-induced colitis. The body weight loss and length change of colon after TNBS instillation were more severe than those in normal mice. AL-1 treatment led to significant reductions in disease activity index (DAI), macroscopic score and colon mucosa damage index (CMDI) associated with TNBS administration. AL-1 inhibited the inflammatory response via lowering the level of inflammatory cytokines and myeloperoxidase (MPO) activity. AL-1 attenuated the expression of p-p65, p-IκBα and COX-2 in the colitis mice. The alleviation of colon injury by AL-1 treatment was also evidenced by the increased expression of PPAR-γ. These results indicated that AL-1 could protect intestinal tract from the injury induced by TNBS in mice, suggesting that AL-1 may have potential in treatment for IBD.
穿心莲内酯是一种传统的草药，在亚洲被广泛用于治疗炎症相关疾病。我们之前的研究发现，穿心莲内酯-硫辛酸缀合物 AL-1 能够缓解炎症。虽然 AL-1 的抗炎活性与其细胞保护作用有关，但 AL-1 是否能改善炎症性肠病（IBD）及其作用机制在很大程度上尚不清楚。在这项研究中，我们研究了 AL-1 在三硝基苯磺酸（TNBS）诱导的结肠炎 C57BL/6 小鼠中的抗炎作用。与正常小鼠相比，TNBS 灌注后小鼠的体重减轻和结肠长度变化更为严重。AL-1 治疗可显著降低与 TNBS 给药相关的疾病活动指数（DAI）、宏观评分和结肠黏膜损伤指数（CMDI）。AL-1 通过降低炎症细胞因子和髓过氧化物酶（MPO）活性来抑制炎症反应。AL-1 还可减弱结肠炎小鼠中 p-p65、p-IκBα 和 COX-2 的表达。AL-1 治疗可增加 PPAR-γ 的表达，从而减轻结肠损伤。这些结果表明，AL-1 可保护肠道免受 TNBS 诱导的损伤，提示 AL-1 可能具有治疗 IBD 的潜力。
