Combination Therapy with Indigo and Indirubin for Ulcerative Colitis via Reinforcing Intestinal Barrier Function

作者：Jin Xie, Shimin Tian, Jun Liu, Shengjie Huang, Ming Yang, Xiangbo Yang, Runchun Xu, Junzhi Lin, Li Han, Dingkun Zhang · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2023 · DOI：10.1155/2023/2894695 · 被引用次数：52 · 研究领域：IL-33, ST2, and ILC Pathways、Immune Cell Function and Interaction、Gut microbiota and health

Indigo and indirubin, the active molecules of traditional Chinese medicine indigo naturalis, exert therapeutic activity for ulcerative colitis (UC). Indigo and indirubin are isomers and have distinctive profiles in anti-inflammation, immune regulation, intestinal microbiota regulation, oxidative stress regulation, and intestinal mucosal repair for UC treatment. Thus, exploring its combined administration’s integrated advantages for UC is critical. This study is aimed at clarifying the effect and mechanisms of the combined administration of indigo and indirubin on colitis mouse models. The results showed that all the treatment groups could improve the disease symptoms, and the combined administration showed the best effect. Additionally, compared with indigo and indirubin alone, the combination group could significantly reinforce intestinal barrier function by increasing the expression of E-cadherin, occludin, ZO-1, and MUC2 and improving intestinal permeability. The treatment groups significantly improved the expression of cytokines, including TNF-α, IFN-γ, IL-12, IL-23, and IL-17A, and indirubin presented the most potent anti-inflammatory effect. Furthermore, all the treatment groups reduced the infiltration of the immune cells in intestinal lamina propria and the production of ROS/RNS. Notably, indigo exhibited a more substantial capacity to regulate natural killer (NK) cells, ILC3, neutrophils, and dendritic cells, followed by the combination group and indirubin alone. Fin...