Abstract | BACKGROUND: METHODS: We established colitis models in HIEC and Caco-2 cells and mice with LPS and DSS, respectively. Additionally, NLRP3 knockout mice and HIEC cells transfected with NLRP3 silencing gene and ML385 illustrated the role of isofraxidin in pyroptosis and oxidative stress. Data from cells and mice analyses were subjected to one-way analysis of variance or a paired t-test. RESULTS:
Isofraxidin significantly alleviated LPS-induced cell inflammation and reduced lactic dehydrogenase release. Isofraxidin also reversed DSS- or LPS-induced pyroptosis in vivo and in vitro, increasing the expression of pyroptosis-related proteins. Moreover, isofraxidin alleviated oxidative stress induced by DSS or LPS, reducing reactive oxidative species (ROS), upregulation nuclear factor erythroid 2-related factor 2 (Nrf2), and promoting its entry into the nucleus. Mechanistically, ML385 reversed the inhibitory effect of isofraxidin on ROS and increased pyroptosis. CONCLUSION:
Isofraxidin can inhibit pyroptosis through upregulating Nrf2, promoting its entry into the nucleus, and reducing ROS, thereby alleviating DSS-induced UC. Our results suggest isofraxidin as a promising therapeutic strategy for UC treatment.
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Authors | Shuang He, Ting Zhang, Yuan-Yi Wang, Wei Yuan, Li Li, Jin Li, Yue-Yan Yang, Dong-Ming Wu, Ying Xu |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 128
Pg. 111570
(Feb 15 2024)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 38280336
(Publication Type: Journal Article)
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Copyright | Copyright © 2024. Published by Elsevier B.V. |
Chemical References |
- NF-E2-Related Factor 2
- Dextran Sulfate
- isofraxidin
- NLR Family, Pyrin Domain-Containing 3 Protein
- Reactive Oxygen Species
- Lipopolysaccharides
- Coumarins
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Topics |
- Mice
- Humans
- Animals
- Colitis, Ulcerative
(drug therapy)
- NF-E2-Related Factor 2
(metabolism)
- Dextran Sulfate
(pharmacology)
- NLR Family, Pyrin Domain-Containing 3 Protein
(metabolism)
- Reactive Oxygen Species
(metabolism)
- Caco-2 Cells
- Lipopolysaccharides
(pharmacology)
- Pyroptosis
- Disease Models, Animal
- Colitis
(chemically induced)
- Inflammation
(pathology)
- Coumarins
(pharmacology)
- Oxidative Stress
- Mice, Inbred C57BL
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