Apigenin Inhibits Tumor Necrosis Factor-α-Induced Production and Gene Expression of Mucin through Regulating Nuclear Factor-Kappa B Signaling Pathway in Airway Epithelial Cells

Seo, Hyo Seok; Sikder, Mohamed Asaduzzaman; Lee, Hyun Jae; Ryu, Jiho; Lee, Choong Jae

doi:10.4062/biomolther.2014.094

Cited by 28 publications

(24 citation statements)

References 27 publications

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“…This study first demonstrates that flavones have anti-inflammatory effects on Muc5AC and iNOS up-regulation as well cytokine secretion in airway epithelial cells. This supports prior studies that apigenin, chrysin, and wogonin inhibit Muc5AC up-regulation in NCI-H292 bronchial cancer cells in response to epidermal growth factor (91,112,113) or TNF␣ (114,115). Our data suggest this occurs partly through direct inhibition of kinase C rather than upstream or downstream mechanisms, as they were directly able to block PKC activity in response to PMA.…”

Section: Discussionsupporting

confidence: 92%

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

Hariri¹,

McMahon²,

Chen³

et al. 2017

Journal of Biological Chemistry

100

176

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Chronic rhinosinusitis has a significant impact on patient quality of life, creates billions of dollars of annual healthcare costs, and accounts for ∼20% of adult antibiotic prescriptions in the United States. Because of the rise of resistant microorganisms, there is a critical need to better understand how to stimulate and/or enhance innate immune responses as a therapeutic modality to treat respiratory infections. We recently identified bitter taste receptors (taste family type 2 receptors, or T2Rs) as important regulators of sinonasal immune responses and potentially important therapeutic targets. Here, we examined the immunomodulatory potential of flavones, a class of flavonoids previously demonstrated to have antibacterial and anti-inflammatory effects. Some flavones are also T2R agonists. We found that several flavones inhibit Muc5AC and inducible NOS up-regulation as well as cytokine release in primary and cultured airway cells in response to several inflammatory stimuli. This occurs at least partly through inhibition of protein kinase C and receptor tyrosine kinase activity. We also demonstrate that sinonasal ciliated epithelial cells express T2R14, which closely co-localizes (<7 nm) with the T2R38 isoform. Heterologously expressed T2R14 responds to multiple flavones. These flavones also activate T2R14-driven calcium signals in primary cells that activate nitric oxide production to increase ciliary beating and mucociliary clearance. polymorphisms encode functional (PAV:roline, lanine, andaline at positions 49, 262, and 296, respectively) or non-functional (AVI: lanine,aline, soleucine at positions 49, 262, and 296, respectively) T2R38. Our data demonstrate that T2R14 in sinonasal cilia is a potential therapeutic target for upper respiratory infections and that flavones may have clinical potential as topical therapeutics, particularly in T2R38 AVI/AVI individuals.

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Section: Discussionsupporting

confidence: 92%

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

Hariri¹,

McMahon²,

Chen³

et al. 2017

Journal of Biological Chemistry

100

176

View full text Add to dashboard Cite

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“…Furthermore, our findings provide evidence of the bioactivity of the EAF and the tested compounds in inflammatory diseases and suggest that they may exert anti-inflammatory effect by inhibiting the pro-inflammatory mediators. Our results are in accordance with the previously reported results for the mechanism of action of trachelogenin, nor-trachelogenin and tracheloside, apigenin, quercetin and luteolin for exerting their antiinflammatory activities through modulation of the cytokine system (Jia et al, 2014;Seo et al, 2014;Zhu et al, 2013;Harrison and Cooper, 2008;Chen et al, 2004;Ueda, 2004;Xagorari et al, 2001;Habtemariam et al, 2000).…”

Section: Discussionsupporting

confidence: 93%

In vivo TNF- and IL-1 inhibitory activity of phenolics isolated from Trachelospermum jasminoides (Lindl.) Lem

Salama

El‐Hawary²,

Mousa³

et al. 2015

J. Med. Plants Res.

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A bio-guided fractionation of the defatted ethanolic extract (DEE) of the aerial parts of Trachelospermum jasminoides and its fractions: ethyl acetate fraction (EAF), chloroform fraction (CF) and n-butanol fraction (BF) were carried out, using carragenan induced rat paw edema method, to evaluate the in vivo acute anti-inflammatory potential at a given dose of 100 mg/kg body weight compared to indomethacin (20 mg/kg body weight). The EAF revealed the highest anti-inflammatory activity (76.92%) relative to the DEE and the CF (63.82 and 48.75%, respectively) at the same tested dose, while the BF was significantly inactive. The EAF and its major isolated compounds were investigated to determine the level of proinflammatory cytokines using enzyme-linked immunosorbant assay (ELISA). Seven major compounds were isolated from the EAF, identified as: trachelogenin, nor-trachelogenin and tracheloside, in addition to apigenin, luteolin, quercetin and luteolin-7-O-β-D-glucopyranoside. Identification of the isolated compounds was achieved by their physico-chemical properties and spectral analysis (1D and 2D NMR). The EAF and the isolated compounds inhibited the excessive production of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β. Furthermore, the liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS) for the bioactive EAF was carried out to complete the phytochemical picture. The results of this study verified that the EAF and the major compounds exert their action through inhibition of TNF-α and IL-1 β.

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“…Apigenin may also increase susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics [ 23 ]. Apiginin can inhibit inflammatory protein kinase C (PKC) [ 31 , 32 ] and nuclear-factor-kappa B (NFκB) [ 33 ] signaling in cells in vitro . The flavone chrysin is from Passiflora and chamomile flowers as well as the Pleurotus ostreatus mushroom [ 18 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Plant flavones enhance antimicrobial activity of respiratory epithelial cell secretions against Pseudomonas aeruginosa

et al. 2017

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Flavones are a class of natural plant secondary metabolites that have anti-inflammatory and anti-bacterial effects. Some flavones also activate the T2R14 bitter taste receptor, which is expressed in motile cilia of the sinonasal epithelium and activates innate immune nitric oxide (NO) production. Flavones may thus be potential therapeutics for respiratory infections. Our objective was to examine the anti-microbial effects of flavones on the common sinonasal pathogens Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa, evaluating both planktonic and biofilm growth. Flavones had only very low-level antibacterial activity alone. They did not reduce biofilm formation, but did reduce production of the important P. aeruginosa inflammatory mediator and ciliotoxin pyocyanin. However, flavones exhibited synergy against P. aeruginosa in the presence of antibiotics or recombinant human lysozyme. They also enhanced the efficacy of antimicrobials secreted by cultured and primary human airway cells grown at air-liquid interface. This suggests that flavones may have anti-gram-negative potential as topical therapeutics when combined with antibiotics or in the context of innate antimicrobials secreted by the respiratory or other epithelia. This may have an additive effect when combined with T2R14-activated NO production. Additional studies are necessary to understand which flavone compounds or mixtures are the most efficacious.

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Apigenin Inhibits Tumor Necrosis Factor-α-Induced Production and Gene Expression of Mucin through Regulating Nuclear Factor-Kappa B Signaling Pathway in Airway Epithelial Cells

Cited by 28 publications

References 27 publications

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor

In vivo TNF- and IL-1 inhibitory activity of phenolics isolated from Trachelospermum jasminoides (Lindl.) Lem

Plant flavones enhance antimicrobial activity of respiratory epithelial cell secretions against Pseudomonas aeruginosa

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