Protective Effect of Naringin on DSS-Induced Ulcerative Colitis in Mice

Area of Science:

• Pharmacology
• Gastroenterology
• Immunology

Background:

• Peroxisome proliferator-activated receptor γ (PPARγ) plays a key anti-inflammatory role in experimental colitis.
• PPARγ activation, particularly through nuclear factor-κB (NF-κB) inhibition, is a promising therapeutic strategy for ulcerative colitis (UC).

Purpose of the Study:

• To investigate the therapeutic potential of naringin in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC).
• To elucidate the underlying mechanisms of naringin's action, focusing on PPARγ activation and its downstream effects.

Main Methods:

• Administration of naringin to mice with DSS-induced colitis.
• Assessment of disease activity index (DAI), colon length, and colonic pathology.
• Evaluation of PPARγ and NF-κB activation, along with MAPK and NLRP3 inflammasome pathways.
• Investigation of tight junction (TJ) protein zonula occludens-1 (ZO-1) expression.
• In vitro validation using a PPARγ inhibitor (GW9662).

Main Results:

• Naringin significantly ameliorated DSS-induced UC symptoms, including reduced DAI, preserved colon length, and attenuated pathological damage.
• Naringin activated PPARγ, leading to the suppression of NF-κB activation.
• The protective effects of naringin were partially reversed by the PPARγ inhibitor GW9662.
• Naringin inhibited the activation of mitogen-activated protein kinase (MAPK) and NLRP3 inflammasome.
• Naringin maintained tight junction (TJ) architecture by regulating ZO-1 expression.

Conclusions:

• Naringin demonstrates significant protective effects against DSS-induced ulcerative colitis in mice.
• Naringin's mechanism involves the activation of PPARγ, subsequent inhibition of NF-κB, and modulation of MAPK and NLRP3 inflammasome pathways.
• Naringin may serve as a potential natural therapeutic agent for ulcerative colitis by preserving intestinal barrier function.