LL202 ameliorates colitis against oxidative stress of macrophage by activation of the Nrf2/HO-1 pathway.

Abstract

LL202, a newly synthesized flavonoid derivative, has been confirmed to inhibit the mitogen-activated protein kinase pathway and activation protein-1 activation in monocytes; however, the anti-inflammatory mechanism has not been clearly studied. Uncontrolled overproduction of reactive oxygen species (ROS) has involved in oxidative damage of inflammatory bowel disease. In this study, we investigated that LL202 reduced lipopolysaccharide (LPS)-induced ROS production and malondialdehyde levels and increased superoxide dismutase, glutathione, and total antioxidant capacity in RAW264.7 cells. Mechanically, LL202 could upregulate heme oxygenase-1 (HO-1) via promoting nuclear translocation of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) to regulate LPS-induced oxidative stress in macrophages. In vivo, we validated the role of LL202 in dextran sulfate sodium- and TNBS-induced colitis models, respectively. The results showed that LL202 decreased the proinflammatory cytokine expression and regulated colonic oxidative stress by activating the Nrf2/HO-1 pathway. In conclusion, our study showed that LL202 exerts an anti-inflammatory effect by enhancing the antioxidant capacity of the Nrf2/HO-1 pathway to macrophages.

• Authors: Yuan Gao, Dongsheng Bai, Yue Zhao, Qin Zhu, Yihui Zhou, Zhiyu Li, Na Lu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 7 Pg. 10625-10639 (07 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30426485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Antioxidants
• Flavonoids
• LL202 flavonoid
• Lipopolysaccharides
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Reactive Oxygen Species
• Trinitrobenzenes
• Dextran Sulfate
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Animals
• Antioxidants (pharmacology)
• Colitis (chemically induced, drug therapy, genetics)
• Dextran Sulfate (toxicity)
• Disease Models, Animal
• Flavonoids (chemistry, pharmacology, therapeutic use)
• Gene Expression Regulation (drug effects)
• Heme Oxygenase-1 (genetics)
• Humans
• Inflammatory Bowel Diseases (drug therapy, genetics)
• Lipopolysaccharides (toxicity)
• Macrophages (drug effects)
• Membrane Proteins (genetics)
• Mice
• NF-E2-Related Factor 2 (genetics)
• Oxidative Stress (drug effects)
• RAW 264.7 Cells
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Trinitrobenzenes (toxicity)