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Updated: Aug 8, 2025
Investigating Intestinal Inflammation in DSS-induced Model of IBD
Published on: February 1, 2012
Ononin alleviates DSS-induced colitis through inhibiting NLRP3 inflammasome via triggering mitophagy
Ting Yu1, Xuejia Lu1, Yan Liang1
1Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People's Republic of China.
Background:
Ononin, a flavonoid isolated from Astragalus membranaceus root, is the active ingredient of A. membranaceus and has potential anti-inflammatory properties, but its effect on colitis is unclear.
Aims:
This study aimed to explore the anticolitis effect of Ononin by establishing a colitis model in mice induced by dextran sulfate sodium (DSS).
Methods:
Male C57BL/6 mice were provided DSS, then treated with Ononin (10, 20, 40 mg/kg) or 5-ASA (40 mg/kg). The colitis symptoms were observed, the disease activity index (DAI) score were recorded daily, and colonic inflammation was evaluted by histopathological scoring. The expression of cytokines, inflammatory mediators, and mitophagy/NLRP3 inflammasome-related proteins were measured.
Results:
Ononin significantly alleviated weight loss and colon shortening in mice with colitis (p < .01). Moreover, Ononin decreased the production of inflammatory cytokines and mediators associated with colitis (p < .05). In addition, Ononin inhibited macrophages infiltration and reduced caspase-1 activation in colitis mice. Caspase-1 activation is closely related to the NLRP3 inflammasome. Therefore, we investigated the effect of Ononin on NLRP3 inflammasome in vitro. The relevant results confirmed that Ononin inhibited NLRP3 inflammasome activation and inhibited mitochondrial damage (p < .05). Further studies revealed that Ononin inhibited mitochondrial damage through triggering mitophagy (p < .05).
Conclusion:
Ononin alleviates DSS-induced colitis by activating mitophagy to inhibit NLRP3 inflammasome.
Insights
Ononin, a compound from Astragalus membranaceus, effectively treats colitis in mice by reducing inflammation. It works by activating mitophagy, which inhibits the NLRP3 inflammasome pathway, offering a potential new therapy for inflammatory bowel disease.
Area of Science:
- Pharmacology
- Inflammation Research
- Gastroenterology
Background:
- Ononin, a flavonoid from Astragalus membranaceus, shows potential anti-inflammatory effects.
- The impact of Ononin on colitis, a form of inflammatory bowel disease, remains largely unexplored.
Purpose of the Study:
- To investigate the therapeutic effects of Ononin on dextran sulfate sodium (DSS)-induced colitis in a mouse model.
- To elucidate the underlying molecular mechanisms, including the role of mitophagy and the NLRP3 inflammasome.
Main Methods:
- A mouse model of colitis was established using DSS.
- Mice were treated with varying doses of Ononin or 5-aminosalicylic acid (5-ASA).
- Colitis severity, inflammatory markers, cytokine expression, and NLRP3 inflammasome pathway components were assessed.
Main Results:
- Ononin significantly reduced colitis symptoms, including weight loss and colon shortening.
- Treatment with Ononin decreased inflammatory cytokines and mediators.
- Ononin inhibited NLRP3 inflammasome activation and macrophage infiltration by triggering mitophagy and reducing mitochondrial damage.
Conclusions:
- Ononin demonstrates significant anticolitis effects in a DSS-induced mouse model.
- The mechanism involves the activation of mitophagy, leading to the inhibition of NLRP3 inflammasome activation.
- Ononin represents a promising therapeutic agent for managing colitis.
