Andrographolide derivative AL-1 reduces intestinal permeability in dextran sulfate sodium (DSS)-induced mice colitis model

• Published in: Life sciences (1973) Vol. 241; p. 117164
• Main Authors: Jiang, Nan, Wei, Yuke, Cen, Yun, Shan, Luchen, Zhang, Zaijun, Yu, Pei, Wang, Yuqiang, Xu, Lipeng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.01.2020
• Subjects: AL-1; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Cell Membrane Permeability - drug effects; Cell Membrane Permeability - physiology; Colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colitis - pathology; Dextran Sulfate - toxicity; Diterpenes - chemistry; Diterpenes - pharmacology; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Male; Mice; Mice, Inbred C57BL; MLCK; Myosin-Light-Chain Kinase - metabolism; Phosphorylation; Signal Transduction; Tight junction; Tight Junctions - drug effects; Tight Junctions - metabolism; Tight Junctions - pathology; MLCK; MUC-2; DSS; MLC2; H&E staining; TNBS; DAI; PVDF; UC; AL-1; SDS-PAGE; ZO-1; Andro; DAO; LA; PAS staining; 5-ASA; Tight junction; JAM-A; Colitis; TJs
• DOI: 10.1016/j.lfs.2019.117164
• ISSN: 0024-3205

This study was to assess whether andrographolide derivative (AL-1) could restore mucosal homeostasis and regulate tight junctions through MLCK-dependent pathway in DSS-induced colitis mice. Colitis mice model was induced by daily administration of 2.5% DSS for seven days. The therapeutic effect was determined by evaluating the histopathological changes and the pro-inflammatory cytokine level. In addition, the effects of AL-1 on tight junctions were examined by immunohistochemistry and Western blot. The expressions of factors in MLCK-dependent pathway were evaluated by immunofluorescence and Western blot. AL-1 protected the intestinal barrier function in DSS-induced colitis mice. These protective effects were achieved by maintaining the normal mucus secretion and preserving tight junctions via suppression of the MLCK-dependent pathway. AL-1 could prevent the increase in the DSS-induced intestinal permeability. These data indicated that AL-1 could be a promising agent for UC treatment.