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Updated: May 28, 2026
DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat
Published on: February 27, 2014
Integrated RNA-seq and network pharmacology analyses suggest PI3K-Akt and NF-κB pathway modulation in the protective
Shuo Wang1,2,3, Cheng Tan1,2,3, Haodong He1,2,3
1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. dongweiguo@whu.edu.cn.
Abstract:
Ulcerative colitis (UC), a chronic inflammatory bowel disease, remains difficult to treat due to incomplete understanding of its mechanisms and limited therapeutic options. Diosmin, a natural citrus-derived flavonoid, has shown promising anti-inflammatory effects, but its molecular mechanisms in UC are unclear. In this study, we investigated the protective role of diosmin using dextran sulfate sodium (DSS)-induced colitis in mice and LPS-stimulated HT-29 cells, integrating transcriptomic and network pharmacology analyses. Diosmin treatment significantly alleviated colitis symptoms, reduced inflammation, preserved colon length, and enhanced intestinal barrier integrity, with efficacy comparable to 5-aminosalicylic acid. RNA-seq and network pharmacology identified PI3K-Akt and NF-κB as key pathways associated with diosmin-mediated protection, while molecular docking was used as a supportive computational analysis to explore potential interactions with selected hub-associated proteins. Experimental validation confirmed that diosmin inhibited activation of PI3K-Akt-mTOR and NF-κB signaling, decreased pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), increased IL-10, promoted intestinal barrier repair via upregulation of ZO-1, occludin, and E-cadherin, and suppressed apoptosis of colonic epithelial cells. Together, these findings suggest that diosmin exerts multi-target protective effects against experimental colitis by modulating inflammation, supporting barrier integrity, and regulating key signaling pathways, providing mechanistic insight into the actions of this citrus-derived bioactive compound in colitis.
Insights
Diosmin, a citrus flavonoid, effectively treats ulcerative colitis (UC) by reducing inflammation and repairing the gut barrier. This study reveals its protective mechanisms via PI3K-Akt and NF-κB pathways.
Area of Science:
- Gastroenterology
- Pharmacology
- Immunology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
- The therapeutic mechanisms of diosmin, a natural flavonoid, in UC are not fully understood.
Purpose of the Study:
- To investigate the protective effects and molecular mechanisms of diosmin in experimental colitis models.
- To elucidate diosmin's role in modulating inflammation and intestinal barrier function.
Main Methods:
- Dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-stimulated HT-29 cells were used.
- Transcriptomic (RNA-seq) and network pharmacology analyses identified key signaling pathways.
- Molecular docking and experimental validation confirmed diosmin's targets and effects.
Main Results:
- Diosmin treatment significantly alleviated colitis symptoms, reduced inflammation, and preserved colon length.
- Key pathways identified include PI3K-Akt-mTOR and NF-κB signaling.
- Diosmin suppressed pro-inflammatory cytokines, enhanced intestinal barrier integrity (ZO-1, occludin, E-cadherin), and reduced apoptosis.
Conclusions:
- Diosmin exhibits multi-target protective effects against experimental colitis.
- It modulates inflammation, supports barrier integrity, and regulates crucial signaling pathways.
- Diosmin offers a promising therapeutic strategy for ulcerative colitis.
