Role of nuclear factor-kappaB and heme oxygenase-1 in the mechanism of action of an anti-inflammatory chalcone derivative in RAW 264.7 cells

British Journal of Pharmacology
M J AlcarazM L Ferrándiz

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 microm) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 microg ml(-1)) due to the inhibition of nuclear factor kappaB (NF-kappaB) activation. We have shown that treatment of cells with CH results in diminished degradation of the NF-kappaB-IkappaB complex leading to inhibition of NF-kappaB 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-kappaB) with a mechanism of action different from antioxidant chalcones.

References

Nov 1, 1992·Archives of Biochemistry and Biophysics·H IschiropoulosJ S Beckman
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·F J StaalL A Herzenberg
Jan 1, 1983·Annual Review of Biochemistry·A Meister, M E Anderson
Mar 1, 1994·The Biochemical Journal·R G Knowles, S Moncada
Sep 1, 1994·The Journal of Experimental Medicine·E MartinQ W Xie
Jan 1, 1996·Nature Medicine·D WillisD A Willoughby
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·M D Maines
Jun 15, 1997·Archives of Biochemistry and Biophysics·F ChenL M Demers
Jul 15, 1997·European Journal of Biochemistry·W K McCoubreyM D Maines
Jan 1, 1999·Bioorganic & Medicinal Chemistry Letters·F HerenciaM J Alcaraz
Sep 3, 1999·The Journal of Biological Chemistry·J AlamJ L Cook
Feb 9, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·I PetracheA M Choi
May 12, 2000·Critical Care Medicine·E Abraham
Aug 5, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·A L TrueA B Malik
Nov 15, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·L E Otterbein, A M Choi
Jan 3, 2001·The Journal of Clinical Investigation·P P Tak, G S Firestein
May 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·R S ArnoldJ D Lambeth
Jun 19, 2001·The Journal of Biological Chemistry·E HeissC Gerhäuser
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·D E Barañano, S H Snyder
Nov 6, 2001·The Journal of Biological Chemistry·Qiang Ma, Krista Kinneer
Feb 21, 2002·Molecular Pharmacology·G ScapagniniR Motterlini
Sep 17, 2002·Antioxidants & Redox Signaling·Stefan W Ryter, Augustine M K Choi
Feb 7, 2003·The Biochemical Journal·Elisabeth BalogunRoberto Motterlini
Mar 26, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ken ItohMasayuki Yamamoto
Oct 17, 2003·The Journal of Pharmacology and Experimental Therapeutics·Ana María VicenteMaría José Alcaraz
Nov 6, 2003·Biochemical Pharmacology·Patricia FernándezMaria José Alcaraz

❮ Previous
Next ❯

Citations

Jun 11, 2008·Neuromolecular Medicine·Tae Gen SonMark P Mattson
Apr 13, 2011·Genes & Nutrition·Barbora OrlikovaMarc Diederich
Jun 25, 2008·The British Journal of Nutrition·Jeremy P E Spencer
Jun 13, 2008·Chemical Research in Toxicology·Philip SawleRoberto Motterlini
Mar 30, 2007·The American Journal of Pathology·Faikah GuelerHermann Haller
Apr 1, 2009·Future Medicinal Chemistry·P Veeraraghavan RamachandranC Max Schmidt
Jan 1, 2014·International Scholarly Research Notices·Rina MondalAsok K Mallik
Jun 6, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Prabhjit KaurSubodh Kumar
Feb 17, 2006·European Journal of Pharmacology·Sung Hee LeeDong Hwan Sohn
Dec 28, 2010·International Immunopharmacology·Vivek R YadavBharat B Aggarwal
Jul 7, 2017·Critical Reviews in Food Science and Nutrition·Lei ChenJianbo Xiao
Jul 25, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Matheus de Freitas SilvaAndrea Tarozzi
Oct 24, 2015·Chemistry : a European Journal·L Alberto JuárezM José Alcaraz
Nov 18, 2005·American Journal of Physiology. Cell Physiology·Hadil AbuarqoubRoberto Motterlini
Nov 13, 2004·The Journal of Pharmacology and Experimental Therapeutics·Roberta ForestiRoberto Motterlini
Mar 4, 2017·Molecular Neurobiology·Aline LongoniAngela T S Wyse
Apr 4, 2018·Journal of Physiology and Biochemistry·Sofija Jovanović StojanovIlijana Grigorov
Dec 2, 2008·Chemical & Pharmaceutical Bulletin·Halise Inci GulJonathan Richard Dimmock
Aug 21, 2010·Journal of Food Science·Keiko SuzukiHiroshi Ishihara
Jan 17, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Temitope Isaac AdelusiXiaoxing Yin
Jun 20, 2006·Biochemical and Biophysical Research Communications·Eva Hernandez-MontesJeremy P E Spencer
Nov 29, 2017·Journal of the American Chemical Society·Cristina de la TorreFélix Sancenón

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.