Integrated RNA-seq and network pharmacology analyses suggest PI3K-Akt and NF-κB pathway modulation in the protective effects of diosmin against experimental colitis

  • Food Funct. 2026 Jun 22;17(12):5521-5537. doi: 10.1039/d6fo01388k.
Shuo Wang  1  2  3 ,  Cheng Tan  1  2  3 ,  Haodong He  1  2  3 ,  Xiangyun Li  1  2  3 ,  Miao Xu  1  2  3 ,  Xingzhou Guo  1  2  3 ,  Yafei Liu  1  2  3 ,  Fei Liao  1  4 ,  Weiguo Dong  1
Affiliations
  • 1. Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. [email protected].
  • 2. Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, 430060, China.
  • 3. Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
  • 4. Wuhan University Shenzhen Research Institute, Shenzhen, Guangdong 518000, China.
PMID: 42191164 DOI: 10.1039/d6fo01388k
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.

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