ReferenceID 1746
Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/β-NF-κB and Keap1-Nrf2 Signalling Pathways
Front Pharmacol
Dehydrocostus lactone (DCL) is a major sesquiterpene lactone isolated from Aucklandia lappa Decne , a traditional Chinese herbal medicine that used to treat gastrointestinal diseases. This study aimed to examine the ther
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Record Fields
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- Reference Id
- 1746
- Evidence Id
- 18336
- Core Evidence Id
- 18336
- Source Reference Id
- 3469
- Herb2 Reference Id
- HBREF004266
- Subject Paper Key
- HBIN023000_35321327
- Pubmed Id
- 35321327
- Doi
- 10.3389/fphar.2022.817596
- Paper Title
- Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/β-NF-κB and Keap1-Nrf2 Signalling Pathways
- Paper Abstract
- Dehydrocostus lactone (DCL) is a major sesquiterpene lactone isolated from Aucklandia lappa Decne , a traditional Chinese herbal medicine that used to treat gastrointestinal diseases. This study aimed to examine the therapeutic effects of DCL on dextran sulfate sodium (DSS)-induced colitis with a focus on identifying the molecular mechanisms involved in DCL-mediated anti-inflammatory activity in macrophages. First, oral administration of DCL (5-15 mg/kg) not only ameliorated symptoms of colitis and colonic barrier injury, but also inhibited the expression of proinflammatory cytokines and myeloperoxidase in colon tissues in DSS-challenged mice. Furthermore, DCL also exhibited significant anti-inflammatory activity in LPS/IFNγ-stimulated RAW264.7 macrophages. Importantly, DCL significantly suppressed the phosphorylation and degradation of IκBα and subsequent NF-κB nuclear translocation, and enhanced the nuclear accumulation of Nrf2 in LPS/IFNγ-treated RAW264.7 cells. Mechanistically, DCL could directly interact with IKKα/β and Keap1, thereby leading to the inhibition of NF-κB signalling and the activation of Nrf2 pathway. Furthermore, DCL-mediated actions were abolished by dithiothreitol, suggesting a thiol-mediated covalent linkage between DCL and IKKα/β or Keap1. These findings demonstrated that DCL ameliorates colitis by targeting NF-κB and Nrf2 signalling, suggesting that DCL may be a promising candidate in the clinical treatment of colitis.
- Journal
- Front Pharmacol
- Publish Year
- 2022
- Experiment Subject
- mouse; ifnγ-stimulated raw264.7 macrophages; ifnγ-treated raw264.7 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Gastrointestinal Diseases; Dcl Ameliorates Colitis; Colitis; Colonic Barrier Injury
- Paper Title Cn
- Paper Title En
- Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/β-NF-κB and Keap1-Nrf2 Signalling Pathways
- Bilingual Status
- semi_complete