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Updated: Jun 4, 2025
Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of the Notch signaling pathway
Linxia Xu1, Wei Liu1, Xixiang Huang1
1Department of Gastroenterology, the First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Bengbu, Anhui, 233000, China.
Objective:
To study the therapeutic effect of sinomenine hydrochloride (SH) on dextran sodium sulfate (DSS)-induced colitis in mice as an animal model and the changes of Notch signaling pathway in colon tissue of mice after treatment.
Methods:
Twenty-four mice were randomly divided into control group, model group, SH low-dose group (20 mg/kg) and SH high-dose group (60 mg/kg), with 6 mice in each group. Disease activity index (DAI), colonic mucosal injury index and colonic histopathological score were calculated. The expression levels of related genes, proteins in Notch signaling pathway and inflammatory factors were quantified.
Results:
SH can significantly reduce the symptoms of colitis mice, and can significantly reduce the DAI score (Model: 3.44 ± 0.27; SH-20: 2.50 ± 0.18; SH-60: 1.89 ± 0.17; P < 0.001) and histopathological injury degree (Model: 7.67 ± 0.52; SH-20: 5.17 ± 0.75, P < 0.01; SH-60: 3.33 ± 0.52, P < 0.001). SH can down-regulate the expression levels of Notch1, NICD1, Jagged1 and Hes1 proteins in colon tissue of colitis mice (Model: 1.92 ± 0.16, 1.83 ± 0.21, 2.23 ± 0.22, 1.91 ± 0.17; SH-20: 1.56 ± 0.12, 1.39 ± 0.13, 1.58 ± 0.12, 1.38 ± 0.11; SH-60: 1.24 ± 0.09, 1.23 ± 0.10, 1.23 ± 0.11, 1.22 ± 0.09; P < 0.01), and reduce the contents of serum pro-inflammatory cytokines TNF-α, IL-1β and IL-6 (Model: 718.53 ± 81.81, 51.62 ± 2.80, 444.07 ± 67.77; SH-20: 544.72 ± 90.03, 34.10 ± 2.90, 345.43 ± 43.40; SH-60: 434.11 ± 71.75, 29.44 ± 3.70, 236.11 ± 29.35; P < 0.001).
Conclusion:
The therapeutic effect of SH on DSS-induced colitis in mice may be related to inhibiting the overactivation of Notch signaling pathway.
Insights
Sinomenine hydrochloride (SH) effectively treats dextran sodium sulfate (DSS)-induced colitis in mice by reducing disease activity and inflammation. This therapeutic effect is linked to the inhibition of the Notch signaling pathway.
Area of Science:
- Gastroenterology
- Pharmacology
- Molecular Biology
Background:
- Inflammatory bowel disease (IBD), including colitis, is a significant health concern with limited effective treatments.
- The Notch signaling pathway plays a critical role in regulating immune responses and tissue homeostasis, and its dysregulation is implicated in IBD pathogenesis.
Purpose of the Study:
- To investigate the therapeutic efficacy of sinomenine hydrochloride (SH) in a mouse model of dextran sodium sulfate (DSS)-induced colitis.
- To elucidate the impact of SH treatment on the Notch signaling pathway in the colonic tissue of mice with colitis.
Main Methods:
- Twenty-four mice were allocated into control, DSS-induced colitis model, and two SH-treated groups (low and high dose).
- Disease activity index (DAI), colonic mucosal injury, and histopathological scores were assessed.
- Expression levels of Notch signaling pathway components (Notch1, NICD1, Jagged1, Hes1) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) were quantified.
Main Results:
- SH treatment significantly ameliorated colitis symptoms, evidenced by reduced DAI scores and histopathological injury.
- SH administration led to a significant downregulation of Notch1, NICD1, Jagged1, and Hes1 protein expression in the colon.
- Treatment with SH markedly decreased serum levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6.
Conclusions:
- Sinomenine hydrochloride demonstrates significant therapeutic potential for DSS-induced colitis in mice.
- The anti-colitis effects of SH are associated with the inhibition of Notch signaling pathway overactivation.
- SH may represent a novel therapeutic agent for managing inflammatory bowel diseases.
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