Chrysanthemum zawadskii var. latilobum extract inhibits the production of nitric oxide and PGE2 through inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(COX-2) in RAW 264. 7 cells

Nuclear factor-κB (NF-κB) is a transcription factor that mediates the inducible expression of a variety of genes involved in immune and inflammatory responses. NF-κB activation induces numerous proinflammatory gene products including cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The divalent heavy metal mercury has been used for thousands of years. Although mercury is clearly toxic to most mammalian organ systems, especially the immune system, exposure has still increased in some areas of the world. However, the underlying toxic mechanism is not clearly identified. Here, we report biochemical evidence that mercury alone induces NF-κB activation, resulting in the induced expression of COX-2 and iNOS. The results suggest that mercury can induce inflammatory diseases by lowering host defense.

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Molecular Docking Prediction and in Vitro Studies Elucidate Anti-inflammatory Effect of Garcinia Extract Against Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Targets

10.21203/rs.3.rs-794705/v1 ◽

2021 ◽

Author(s):

Anuradha Kalita ◽

MANAS DAS ◽

Bhabajyoti Das ◽

Momita Rani Baro

Keyword(s):

Nitric Oxide ◽

Molecular Docking ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Cyclooxygenase 2 ◽

Herbal Extract ◽

Cox 2 ◽

Anti Inflammatory ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Abstract Garcinia is a tropical plant that has been traditionally used in medicinal folklore for its potential antioxidant, antibacterial, anti-hyperlipidemic, anti-diabetic, hepatoprotective, etc. In this study, Garcinia herbal extract (GHE) and one of its important phytocompound (garcinol) were evaluated for their inhibitory action against important inflammatory markers inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. iNOS and COX-2 plays an major role in the process of inflammation and inhibition of these molecules will help to alleviate the inflammatory process. The cells were pre-treated with two doses of Garcinia (230µg/ml and 115µg/ml); garcinol (12µM and 6µM) followed by stimulation with 1µg/ml of LPS for 24h. The results of the study demonstrated that GHE and garcinol plays an important role in suppressing LPS- induced relative mRNA expression of iNOS, COX-2 and subsequent reduction in the levels of nitric oxide and prostaglandin E 2 . Molecular docking analysis of garcinol and hydroxycitric acid, the major active components of GHE with iNOS and COX-2 proteins showed potent interaction with low binding energies. This study suggests that GHE (containing high percentage of HCA) and garcinol may possess anti-inflammatory activity thus providing a possibility for drug designing as iNOS and COX-2 inhibitors.

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Effect ofHelicobacter pylori eradication on cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression during gastric adaptation to aspirin (ASA) in humans

Microscopy Research and Technique ◽

10.1002/jemt.1101 ◽

2001 ◽

Vol 53 (5) ◽

pp. 336-342 ◽

Cited By ~ 1

Author(s):

Harald Fischer ◽

Veronika Huber ◽

Peter Boknik ◽

Hartmut Luess ◽

Joachim Neumann ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Inos Expression ◽

Cyclooxygenase 2 ◽

Cox 2 ◽

Oxide Synthase ◽

Inducible Nitric Oxide

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Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding

Blood ◽

10.1182/blood-2005-09-3691 ◽

2006 ◽

Vol 108 (2) ◽

pp. 518-524 ◽

Cited By ~ 149

Author(s):

Wu-Guo Deng ◽

Shao-Tzu Tang ◽

Hui-Ping Tseng ◽

Kenneth K. Wu

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Nuclear Translocation ◽

Cyclooxygenase 2 ◽

Raw 264.7 Cells ◽

Dependent Manner ◽

Cox 2 ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Melatonin has been shown to be produced by nonpineal cells and possess anti-inflammatory actions in animal models. In the present study, we tested the hypothesis that melatonin suppresses the expression of proinflammatory genes such as cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (INOS) by a common transcriptional mechanism. Melatonin but not tryptophan or serotonin inhibited lipopolysaccharide (LPS)–induced COX-2 and iNOS protein levels and promoter activities in RAW 264.7 cells in a time- and concentration-dependent manner. LPS or LPS plus interferon-γ (IFNγ) increased binding of all 5 isoforms of NF-κB to COX-2 and iNOS promoters. Melatonin selectively inhibited p52 binding without affecting p100 expression, p52 generation from p100, or p52 nuclear translocation. p52 acetylation was enhanced by LPS, which was abrogated by melatonin. Melatonin inhibited p300 histone acetyltransferase (HAT) activity and abrogated p300-augmented COX-2 and iNOS expression. HAT inhibitors suppressed LPS-induced p52 binding and acetylation to an extent similar to melatonin, and melatonin did not potentiate the effect of HAT inhibitors. These results suggest that melatonin inhibits COX-2 and iNOS transcriptional activation by inhibiting p300 HAT activity, thereby suppressing p52 acetylation, binding, and transactivation.

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