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Updated: Jun 23, 2026
10:21
Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
Rutin attenuates liver fibrosis via the IRG1-itaconate-Nrf2 axis
Ningman Jiang1,2, Jiao Zhang2, Ge Kuang2
1Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Summary
The natural compound rutin protects the liver from fibrosis by targeting immune-responsive gene 1 (IRG1). This interaction enhances antioxidant and anti-inflammatory pathways, offering a potential therapeutic strategy for liver disease.
Area of Science:
- Hepatology
- Pharmacology
- Immunology
Background:
- Liver fibrosis results from chronic liver injury, involving inflammation, oxidative stress, and extracellular matrix buildup.
- The flavonoid rutin has known antioxidant and anti-inflammatory effects, with potential liver protection, but its anti-fibrotic mechanism requires clarification.
Purpose of the Study:
- To investigate rutin's protective effects against carbon tetrachloride (CCl₄)-induced liver fibrosis in mice.
- To elucidate the molecular mechanism, focusing on the role of immune-responsive gene 1 (IRG1).
Main Methods:
- Liver fibrosis induced by CCl₄ in mice.
- Evaluated hepatic injury, collagen deposition, inflammation, and oxidative stress using various assays.
- Assessed IRG1's role using IRG1-deficient mice and examined rutin-IRG1 interaction via molecular docking, simulations, and CETSA.
Main Results:
- Rutin treatment reduced CCl₄-induced liver injury, fibrosis, inflammation, and oxidative stress.
- Rutin directly bound and stabilized IRG1, boosting its activity and itaconate production.
- This activated Nrf2 antioxidant signaling and suppressed NLRP3 inflammasome, with effects abolished in IRG1-deficient mice.
Conclusions:
- Rutin acts as a potential anti-fibrotic agent by targeting the IRG1/itaconate pathway.
- This mechanism coordinates antioxidant and anti-inflammatory responses in liver fibrosis.
- IRG1 is crucial for rutin's hepatoprotective effects.
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