Quercetin inhibits neutrophil extracellular traps release and their cytotoxic effects on A549 cells, as well the release and enzymatic activity of elastase and myeloperoxidase

Pereira, Gabriela Sterle; Percebom, I.; Mendes, Susana; Souza, Priscila Silva Sampaio de; Diniz, Larissa Figueiredo Alves; Costa, M. F. da; Lopes, Bruno Rafael Pereira; Toledo, Karina Alves

doi:10.1590/1519-6984.252936

Cited by 5 publications

(8 citation statements)

References 38 publications

(42 reference statements)

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“…The ability of quercetin to regulate the Toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B (TLR4/NF-κB) signaling pathway has also been evaluated [28], showing the ability to inhibit reactive oxygen species (ROS) production and pro-inflammatory cytokine expression. Quercetin also inhibits neutrophil extracellular traps (NETs)' release as well the release and enzymatic activity of elastase and myeloperoxidase [29], a common phenomenon shown in arthritis [30]. Furthermore, quercetin also protects A549 cells from the cytotoxicity induced by NETs at concentrations not exceeding 18 µg/mL [29].…”

Section: Quercetinmentioning

confidence: 99%

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Flavonoids and Flavonoid-Based Nanoparticles for Osteoarthritis and Rheumatoid Arthritis Management

Wahnou,

Limami,

Oudghiri

2024

BioChem

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Arthritis, a global health burden comprising osteoarthritis and rheumatoid arthritis, demands advanced therapeutic approaches. In this context, flavonoids, a diverse group of naturally occurring compounds abundant in fruits, vegetables, and medicinal plants, have emerged as promising candidates for mitigating the inflammatory processes associated with arthritic conditions. This review aims, first, to provide a comprehensive exploration of the potential of flavonoids, focusing on specific compounds such as quercetin, epigallocatechin-3-gallate (EGCG), apigenin, luteolin, fisetin, silibinin, kaempferol, naringenin, and myricetin. The second section of this review delves into the anti-arthritic activities of these flavonoids, drawing insights from clinical trials and scientific studies. Each flavonoid is scrutinized individually to elucidate its mechanisms of action and therapeutic efficacy in the context of both osteoarthritis and rheumatoid arthritis. The third section of this review highlights the challenges associated with harnessing flavonoids for anti-inflammatory purposes. Bioavailability limitations pose a significant hurdle, prompting the exploration of innovative strategies such as the use of nanoparticles as delivery vehicles. In response to these challenges, the fourth section focuses on the emerging field of flavonoid-based nanoparticles. This includes detailed discussions on quercetin, EGCG, fisetin, and naringenin-based nanoparticles, highlighting formulation strategies and preclinical evidence supporting their potential in arthritis management. The targeted delivery to inflammatory sites and the exploration of synergistic combinations with other compounds are also discussed as promising avenues to enhance the therapeutic impact of flavonoids. This review consolidates current knowledge on flavonoids and their nanoformulations as potential therapeutic interventions for osteoarthritis and rheumatoid arthritis. By addressing challenges and presenting future research directions, this review aims to contribute to the advancement of innovative and effective strategies for alleviating the global burden of arthritis.

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Section: Quercetinmentioning

confidence: 99%

“…Quercetin also inhibits neutrophil extracellular traps (NETs)' release as well the release and enzymatic activity of elastase and myeloperoxidase [29], a common phenomenon shown in arthritis [30]. Furthermore, quercetin also protects A549 cells from the cytotoxicity induced by NETs at concentrations not exceeding 18 µg/mL [29].…”

Section: Quercetinmentioning

confidence: 99%

Flavonoids and Flavonoid-Based Nanoparticles for Osteoarthritis and Rheumatoid Arthritis Management

Wahnou,

Limami,

Oudghiri

2024

BioChem

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“…MPO is also associated with the formation of neutrophil extracellular traps (NETs), which can modulate the inflammatory process and induce tissue damage [56]. In human neutrophils, prior incubation with Que reduced NET release after PMA stimulation [57]. Moreover, NETs have a cytotoxic effect on the A549 cell line, and Que was able to reduce the cytotoxic effects of NETs, probably acting by reducing MPO and elastase activity [57].…”

Section: Myeloperoxidasementioning

confidence: 99%

“…In human neutrophils, prior incubation with Que reduced NET release after PMA stimulation [57]. Moreover, NETs have a cytotoxic effect on the A549 cell line, and Que was able to reduce the cytotoxic effects of NETs, probably acting by reducing MPO and elastase activity [57].…”

Section: Myeloperoxidasementioning

confidence: 99%

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Inhibitory Effect of Quercetin on Oxidative Endogen Enzyme: A Focus on Putative Binding Modes

Olla,

Siguri,

Fais

et al. 2023

Preprint

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Oxidative stress is defined as an imbalance between the production of free radicals and reactive oxygen species (ROS) and the ability of the body to neutralize them by antioxidant defense systems. Cells produce ROS as a control of physiological processes, but increasing ROS becomes pathological leading to non-specific and irreversible damage to biological molecules, such as DNA, lipid, and protein. Endogenous ROS are mainly produced by mitochondria during both physiological and pathological conditions, and enzymes, such as nicotinamide adenine dinucleotide phosphate oxidase (NOX), xanthine oxidase (XO), lipoxygenase (LOX), myeloperoxidase (MPO) and monoamine oxidase (MAO). To neutralize ROS, the body employs enzymatic and non-enzymatic defense systems. The dietary intake of bioactive phenols, such as quercetin (Que), is a non-enzymatic system that can quench ROS and protect from pro-oxidative damage. In this review, we evaluate the ability of Que to target endogenous oxidant enzymes involved in ROS production and explore the mechanisms of action underlying its antioxidant properties. Que not only acts as a free radical scavenger by donating electrons through the negative charges in its phenolic and ketone groups, but it can effectively inhibit the activity of several endogenous oxidative enzymes, binding them with high affinity and specificity. Among all targets, Que showed the best results in molecular docking simulations with XO, followed by MAO-A, 5-LOX, NOX, and MPO. Taken together, these findings highlight the potential of Que as a natural antioxidant therapy for oxidative stress-related diseases.

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Trapping DNA-radicals with DMPO reduced hypochlorous acid-induced 8-oxo-7,8-dihydro-2’-deoxyguanosine and mutagenesis in lung epithelial cells

Ramirez,

Gomez Mejiba

2024

Preprint

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Irritation causes the recruitment and activation of neutrophils in the stressed airways. This process is known as neutrophilic inflammation. This process results in myeloperoxidase (MPO), an enzyme contained inside neutrophil azurophilic granules, being released as neutrophil extracellular traps (NETs), which also contain genomic DNA, modified histones, and other proteins. In the airways, released MPO can be taken up by bystander tissue epithelial cells. MPO is the only mammalian peroxidase enzyme that under physiological conditions produces hypochlorite (HOCl). Intracellularly produced HOCl may damage the cell genome, with the intermediacy of DNA-centered free radicals, which upon reaction with molecular oxygen decay to mutagenic end-oxidation products, such as 8-oxo-7,8-dihydro-2’ –deoxyguanosine (8-oxo-dGuo). Herein, we aimed to test whether HOCl-induced DNA-centered radicals precede the oxidation of DNA and mutagenesis in A549 human lung epithelial cells as anin vitromodel that resembles neutrophilic inflammation in irritated airways. Interestingly, by trapping HOCl-induced DNA-centered radicals, the nitrone spin trap 5,5-dimethyl-1-pyrrolineN-oxide (DMPO) blocks the formation of 8-oxo-dGuo and possibly other end-oxidation products, forming DNA-DMPO nitrone adducts, thus reducing mutagenesis in the hypoxanthine phosphoribosyl transferase (hrpt)gene, one of the most sensitive genes to oxidative damage. P53 is a transcription factor known as the master regulator of the cell response to genomic damage. By trapping DNA-centered radicals, DMPO also blocks the translocation of p53 to the cell nucleus, suggesting that by trapping DNA-centered radicals with DMPO, end-oxidation products are prevented, and the cell response to genomic damage is not sensed. DMPO traps DNA-centered radicals, reduces 8-oxo-dGuo accumulation, and blockshrptgene mutation. Trapping DNA-centered radicals to reduce the accumulation of HOCl-induced mutagenic end-oxidation products in the genome of bystander cells, which have taken MPO from the inflammatory milieu, will provide new therapeutic avenues to reduce genotoxic damage at sites of neutrophilic inflammation, such as in the irritated airways.

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Quercetin inhibits neutrophil extracellular traps release and their cytotoxic effects on A549 cells, as well the release and enzymatic activity of elastase and myeloperoxidase

Cited by 5 publications

References 38 publications

Flavonoids and Flavonoid-Based Nanoparticles for Osteoarthritis and Rheumatoid Arthritis Management

Flavonoids and Flavonoid-Based Nanoparticles for Osteoarthritis and Rheumatoid Arthritis Management

Inhibitory Effect of Quercetin on Oxidative Endogen Enzyme: A Focus on Putative Binding Modes

Trapping DNA-radicals with DMPO reduced hypochlorous acid-induced 8-oxo-7,8-dihydro-2’-deoxyguanosine and mutagenesis in lung epithelial cells

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