Role of nuclear factor‐κB and heme oxygenase‐1 in the mechanism of action of an anti‐inflammatory chalcone derivative in RAW 264.7 cells
The synthetic chalcone 3′,4′,5′,3,4,5‐hexamethoxy‐chalcone (CH) is an anti‐inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound. CH (10–30 μM) prevents the o...
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| Published in | British journal of pharmacology Vol. 142; no. 7; pp. 1191 - 1199 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.08.2004
Nature Publishing |
| Subjects | |
| Online Access | Get full text |
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| Abstract | The synthetic chalcone 3′,4′,5′,3,4,5‐hexamethoxy‐chalcone (CH) is an anti‐inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound.
CH (10–30 μM) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 μg ml−1) due to the inhibition of nuclear factor κB (NF‐κB) activation.
We have shown that treatment of cells with CH results in diminished degradation of the NF‐κB–IκB complex leading to inhibition of NF‐κB translocation into the nucleus, DNA binding and transcriptional activity.
We also demonstrate the ability of this compound to activate NfE2‐related factor (Nrf2) and induce heme oxygenase‐1 (HO‐1).
Our results indicate that CH determines a rapid but nontoxic increase of intracellular oxidative species, which could be responsible for Nrf2 activation and HO‐1 induction by this chalcone derivative.
This novel anti‐inflammatory agent simultaneously induces a cytoprotective response (HO‐1) and downregulates an inflammatory pathway (NF‐κB) with a mechanism of action different from antioxidant chalcones.
British Journal of Pharmacology (2004) 142, 1191–1199. doi:10.1038/sj.bjp.0705821 |
|---|---|
| AbstractList | The synthetic chalcone 3′,4′,5′,3,4,5‐hexamethoxy‐chalcone (CH) is an anti‐inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound.
CH (10–30 μM) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 μg ml−1) due to the inhibition of nuclear factor κB (NF‐κB) activation.
We have shown that treatment of cells with CH results in diminished degradation of the NF‐κB–IκB complex leading to inhibition of NF‐κB translocation into the nucleus, DNA binding and transcriptional activity.
We also demonstrate the ability of this compound to activate NfE2‐related factor (Nrf2) and induce heme oxygenase‐1 (HO‐1).
Our results indicate that CH determines a rapid but nontoxic increase of intracellular oxidative species, which could be responsible for Nrf2 activation and HO‐1 induction by this chalcone derivative.
This novel anti‐inflammatory agent simultaneously induces a cytoprotective response (HO‐1) and downregulates an inflammatory pathway (NF‐κB) with a mechanism of action different from antioxidant chalcones.
British Journal of Pharmacology (2004) 142, 1191–1199. doi:10.1038/sj.bjp.0705821 The synthetic chalcone 3′,4′,5′,3,4,5-hexamethoxy-chalcone (CH) is an anti-inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound. CH (10–30 μ M ) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 μ g ml −1 ) due to the inhibition of nuclear factor κ B (NF- κ B) activation. We have shown that treatment of cells with CH results in diminished degradation of the NF- κ B–I κ B complex leading to inhibition of NF- κ B translocation into the nucleus, DNA binding and transcriptional activity. We also demonstrate the ability of this compound to activate NfE2-related factor (Nrf2) and induce heme oxygenase-1 (HO-1). Our results indicate that CH determines a rapid but nontoxic increase of intracellular oxidative species, which could be responsible for Nrf2 activation and HO-1 induction by this chalcone derivative. This novel anti-inflammatory agent simultaneously induces a cytoprotective response (HO-1) and downregulates an inflammatory pathway (NF- κ B) with a mechanism of action different from antioxidant chalcones. The synthetic chalcone 3′,4′,5′,3,4,5‐hexamethoxy‐chalcone (CH) is an anti‐inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound. CH (10–30 μ M ) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 μ g ml −1 ) due to the inhibition of nuclear factor κ B (NF‐ κ B) activation. We have shown that treatment of cells with CH results in diminished degradation of the NF‐ κ B–I κ B complex leading to inhibition of NF‐ κ B translocation into the nucleus, DNA binding and transcriptional activity. We also demonstrate the ability of this compound to activate NfE2‐related factor (Nrf2) and induce heme oxygenase‐1 (HO‐1). Our results indicate that CH determines a rapid but nontoxic increase of intracellular oxidative species, which could be responsible for Nrf2 activation and HO‐1 induction by this chalcone derivative. This novel anti‐inflammatory agent simultaneously induces a cytoprotective response (HO‐1) and downregulates an inflammatory pathway (NF‐ κ B) with a mechanism of action different from antioxidant chalcones. British Journal of Pharmacology (2004) 142 , 1191–1199. doi: 10.1038/sj.bjp.0705821 |
| Author | Araico, Amparo Alcaraz, María José Terencio, María Carmen Vicente, Ana María Ferrándiz, María Luisa Dominguez, José N |
| AuthorAffiliation | 1 1 Department of Pharmacology, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjasot, Valencia, Spain 2 2 Laboratory of Organic Synthesis, Central University of Venezuela, Caracas 1051, Venezuela |
| AuthorAffiliation_xml | – name: 1 1 Department of Pharmacology, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjasot, Valencia, Spain – name: 2 2 Laboratory of Organic Synthesis, Central University of Venezuela, Caracas 1051, Venezuela |
| Author_xml | – sequence: 1 givenname: María José surname: Alcaraz fullname: Alcaraz, María José – sequence: 2 givenname: Ana María surname: Vicente fullname: Vicente, Ana María – sequence: 3 givenname: Amparo surname: Araico fullname: Araico, Amparo – sequence: 4 givenname: José N surname: Dominguez fullname: Dominguez, José N – sequence: 5 givenname: María Carmen surname: Terencio fullname: Terencio, María Carmen – sequence: 6 givenname: María Luisa surname: Ferrándiz fullname: Ferrándiz, María Luisa |
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| Keywords | heme oxygenase NfE2-related factor Enzyme Antiinflammatory agent Chalcone Oxygenase nuclear factor-κB Nitric oxide Heme 3',4',5',3,4,5-Hexamethoxy-chalcone Oxidoreductases Transcription factor NFκB Mechanism of action |
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| Snippet | The synthetic chalcone 3′,4′,5′,3,4,5‐hexamethoxy‐chalcone (CH) is an anti‐inflammatory compound able to reduce nitric oxide (NO) production by inhibition of... The synthetic chalcone 3′,4′,5′,3,4,5-hexamethoxy-chalcone (CH) is an anti-inflammatory compound able to reduce nitric oxide (NO) production by inhibition of... |
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| SubjectTerms | 3′,4′,5′,3,4,5‐Hexamethoxy‐chalcone Biological and medical sciences heme oxygenase Medical sciences NfE2‐related factor nitric oxide nuclear factor‐κB Pharmacology. Drug treatments |
| Title | Role of nuclear factor‐κB and heme oxygenase‐1 in the mechanism of action of an anti‐inflammatory chalcone derivative in RAW 264.7 cells |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1038%2Fsj.bjp.0705821 https://pubmed.ncbi.nlm.nih.gov/PMC1575177 |
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