The Suppressive Effect of Quercetin on Toll-Like Receptor 7-Mediated Activation in Alveolar Macrophages

Yasui, Masayoshi; Matsushima, Miyoko; Omura, Aya; Mori, Kanae; Ogasawara, Nanako; Kodera, Yuka; Shiga, Marika; Ito, Komei; Kojima, Seiji; Kawabe, Tsutomu

doi:10.1159/000438993

Cited by 24 publications

(15 citation statements)

References 37 publications

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“…Liu, Xue, Li, Ao, & Lu, 2013), as well as LPS-induced lung injury (Huang, Zhong, & Wu, 2015). The beneficial effect of Quercetin involving TLR modulation was further established in a study on mouse alveolar macrophage cultures, where Quercetin attenuated TLR7-induced expression of TNF-α and IL-6 (Yasui, et al, 2015). Finally, in another study on LPS-stimulated human peripheral blood mononuclear cells (PBMCs), Quercetin was able to suppress the secretion of TNF-α, IL-1β, and IL-6 from PBMCs, and reduced the mRNA expression of TLR2 and NF-κB (M.…”

Section: Pharmacological Approaches Targeting Tlr/nf-κb and Oxidatmentioning

confidence: 99%

Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets

Mishra

Banga

Silveyra

2018

Pharmacology & Therapeutics

220

127

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Asthma is a complex inflammatory disease characterized by airway inflammation and hyperresponsiveness. The mechanisms associated with the development and progression of asthma have been widely studied in multiple populations and animal models, and these have revealed involvement of various cell types and activation of intracellular signaling pathways that result in activation of inflammatory genes. Significant contributions of Toll-like-receptors (TLRs) and transcription factors such as NF-кB, have been reported as major contributors to inflammatory pathways. These have also recently been associated with mechanisms of oxidative biology. This is of important clinical significance as the observed inefficacy of current available treatments for severe asthma is widely attributed to oxidative stress. Therefore, targeting oxidizing molecules in conjunction with inflammatory mediators and transcription factors may present a novel therapeutic strategy for asthma. In this review, we summarize TLRs and NF-кB pathways in the context of exacerbation of asthma pathogenesis and oxidative biology, and we discuss the potential use of polyphenolic flavonoid compounds, known to target these pathways and possess antioxidant activity, as potential therapeutic agents for asthma.

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Section: Pharmacological Approaches Targeting Tlr/nf-κb and Oxidatmentioning

confidence: 99%

Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets

Mishra

Banga

Silveyra

2018

Pharmacology & Therapeutics

220

127

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“…Earlier pharmacological studies have shown that flavonoids, chemical constituents of traditional Chinese medicine, have anti-inflammatory and analgesic effects. At the same time, they played anti-inflammatory effects through other pathways and regulation of inflammatory mediators such as IL-1β, IL-6, and TNF-α and their receptors ( Li et al, 2015 ; Yasui et al, 2015 ). In this study, most of the flavonoids were extracted by systematic solvent method.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and Analgesic Effects of Polygonum orientale L. Extracts

et al. 2017

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Background and Purpose: Polygonum orientale L. (family: Polygonaceae), named Hongcao in China, is a Traditional Chinese Medicinal and has long been used for rheumatic arthralgia and rheumatoid arthritis. However, no pharmacological and mechanism study to confirm these clinic effects have been published. In this investigation, the anti-inflammatory, analgesic effects and representative active ingredient compounds of P. orientale have been studied.Methods: Dried small pieces of the stems and leaves of P. orientale were decocted with water and partitioned successively to obtain ethyl acetate and ethyl ether extract of P. orientale (POEa and POEe). Chemical compositions of them were analyzed by UPLC-Q-Exactive HRMS. Anti-inflammatory and analgesic effects of POEa and POEe were evaluated using xylene induced ear edema, carrageenan induced paw edema, Freunds’ complete adjuvant induced arthritis, and formaldehyde induced pain in rat. Their mechanisms of anti-inflammatory and analgesic effects were also studied via assays of TNF-α, IL-1β, IL-6, and PGE2 in serum.Results: UPLC-Q-Exactive HRMS analysis showed that POEa and POEe mainly contained flavonoids including orientin, isoorientin, vitexin, luteolin, and quercetin. Furthermore, anti-inflammatory effects of POEa and POEe were evident in xylene induced ear edema. The paw edema in Freund’s complete adjuvant and carrageenan were significantly (P < 0.05, 0.01) inhibited by POEa (5, 7.5 g/kg). POEe (7.5 g/kg) was significantly (P < 0.05, 0.01) inhibited Freunds’ complete adjuvant induced paw edema and cotton pellet induced granuloma formation. Similarly, POEe significantly (P < 0.05, 0.01) inhibited the pain sensation in acetic acid induced writhing test. POEa (5, 7.5 g/kg) significantly (P < 0.05, 0.01) inhibited formaldehyde induced pain in both phases. POEa (7.5 g/kg) markedly (P < 0.05) prolonged the latency period of hot plate test after 30 and 60 min. The concentrations of TNF-α, IL-1β, IL-6, and PGE2 were significantly (P < 0.01) decreased by POEa (3.75, 5 g/kg).Conclusion: POEa and POEe have anti-inflammatory and analgesic effects, which was mainly relevant to the presence of flavonoids, including orientin, isoorientin, vitexin, luteolin, and quercetin. The mechanism of anti-inflammatory and analgesic effects of POEa may be to decrease the concentrations of TNF-α, IL-1β, IL-6, and PGE2 in serum.

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“…Although quercetin has previously been reported to exert anti-inflammatory effects via modulation of Nrf2-signaling, these observations have mainly been made in models of acute lung injury or viral and bacterial infections (44) (45,46). Only a few studies have investigated the Nrf2-modulating effect of quercetin in relation to fibrosis, but these studies have focused on other organs including the heart (47) and liver (48).…”

Section: Discussionmentioning

confidence: 99%

The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice

Boots

Veith

Albrecht

et al. 2020

Preprint

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Background Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of which the etiology is still not fully understood. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Quercetin is a dietary antioxidant with strong redox modulating capacities that is suggested to exert part of its antioxidative effects via activation of the redox-sensitive transcription factor Nrf2 that regulates endogenous antioxidant levels. Therefore, the aim of the present study was to investigate if the dietary antioxidant quercetin can exert anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrogenesis through Nrf2-dependent restoration of redox imbalance. Methods Homozygous Nrf2 deficient mice and their wildtype littermates were fed a control diet without or with 800 mg quercetin per kg diet from 7 days prior to a single 1 µg/2µl per g BW bleomycin challenge until they were sacrificed 14 days afterwards. Lung tissue and plasma were collected to determine markers of fibrosis (expression of extracellular matrix genes and histopathology), inflammation (pulmonary gene expression and plasma levels of Tumor Necrosis Factor-α (TNFα) and Keratinocyte Chemoattrachtant (KC)), and redox balance (pulmonary gene expression of antioxidants and malondialdehyde-dG (MDA)- DNA adducts). Results Mice fed the enriched diet for 7 days prior to the bleomycin challenge had significantly enhanced plasma and pulmonary quercetin levels (11.08 ± 0.73 µM versus 7.05 ± 0.2 µM) combined with increased expression of Nrf2 and Nrf2-responsive genes compared to mice fed the control diet in lung tissue. Upon bleomycin treatment, quercetin-fed mice displayed reduced expression of collagen (COL1A2) and fibronectin (FN1) and a tendency of reduced inflammatory lesions (2.8 ± 0.7 versus 1.9 ± 0.8). These beneficial effects were accompanied by reduced pulmonary gene expression of TNFα and KC, but not their plasma levels, and enhanced Nrf2-induced pulmonary antioxidant defences. In Nrf2 deficient mice, no effect of the dietary antioxidant on either histology or inflammatory lesions was observed. Conclusion Quercetin exerts anti-fibrogenic and anti-inflammatory effects on bleomycin-induced pulmonary damage in mice possibly through modulation of the redox balance by inducing Nrf2. However, quercetin could not rescue the bleomycin-induced pulmonary damage indicating that quercetin alone cannot ameliorate the progression of IPF.

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The Suppressive Effect of Quercetin on Toll-Like Receptor 7-Mediated Activation in Alveolar Macrophages

Cited by 24 publications

References 37 publications

Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets

Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets

Anti-inflammatory and Analgesic Effects of Polygonum orientale L. Extracts

The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice

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