Affiliation:
1. State Key Laboratory of Characteristic Chinese Drug Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2. Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
3. State Key Laboratory of Innovation Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
4. Yaan Xunkang Pharmaceutical Co., Ltd., Yaan 625600, China
5. TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
Abstract
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. Finally, all the treatment groups modulated intestinal microbiota composition, increased the proportion of beneficial microbiota, and decreased the proportion of microbiota. Our results indicated that indigo and indirubin synergistically reinforced the intestinal barrier function, which may be associated with integrating the indirubin anti-inflammatory and intestinal microbiota regulating strength and indigo immune and ROS/RNS regulation advantage.
Funder
National Natural Science Foundation of China
Subject
Cell Biology,Aging,General Medicine,Biochemistry