Coptisine ameliorates DSS-induced ulcerative colitis via improving intestinal barrier dysfunction and suppressing...

Area of Science:

• Pharmacology
• Immunology
• Gastroenterology

Background:

• Ulcerative colitis (UC) is a chronic autoimmune disease with unsatisfactory treatment options.
• Rhizoma Coptidis, a traditional Chinese medicine, contains active compounds like coptisine (COP) with potential therapeutic benefits.
• Existing treatments for UC are limited, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

• To evaluate the efficacy of coptisine (COP) in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC).
• To elucidate the underlying mechanisms by which COP exerts its anti-inflammatory and protective effects on the colon.

Main Methods:

• Administration of COP to DSS-induced colitis mice at varying doses (50 and 100 mg/kg).
• Assessment of clinical symptoms including body weight loss and disease activity index (DAI).
• Histopathological analysis (HE staining), Western blot for tight junction proteins and apoptosis markers, and measurement of inflammatory mediators (MPO, cytokines).

Main Results:

• COP treatment significantly alleviated clinical symptoms of colitis, including reduced body weight loss and DAI scores.
• COP preserved colon length and protected intestinal barrier integrity, evidenced by improved HE staining and enhanced tight junction protein expression.
• COP inhibited inflammatory cell infiltration, suppressed pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-17), and reduced apoptosis, while increasing anti-inflammatory cytokines (IL-10, TGF-β).
• COP's mechanism involves inhibiting IκBα phosphorylation and NF-κB p65 translocation.

Conclusions:

• Coptisine (COP) demonstrates significant therapeutic potential in ameliorating DSS-induced ulcerative colitis (UC) in mice.
• COP acts by maintaining intestinal epithelial barrier integrity, inhibiting apoptosis, and suppressing inflammatory responses.
• COP's anti-inflammatory effects are mediated through the inhibition of the NF-κB signaling pathway.