The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral Blood Mononuclear Cells via Modulation of the NF-κβ System

Abstract

The flavonoids comprise a large class of low-molecular-weight plant metabolites ubiquitously distributed in food plants. These dietary antioxidants exert significant antitumor, antiallergic, and anti-inflammatory effects. The molecular mechanisms of their biological effects remain to be clearly understood. We investigated the anti-inflammatory potentials of a safe, common dietary flavonoid component, quercetin, for its ability to modulate the production and gene expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-␣) by human peripheral blood mononuclear cells (PBMC). Our results showed that quercetin significantly inhibited TNF-␣ production and gene expression in a dose-dependent manner. Our results provide direct evidence of the anti-inflammatory effects of quercetin by PBMC, which are mediated by the inhibition of the proinflammatory cytokine TNF-␣ via modulation of NF-␤1 and I␤.The natural antioxidant flavonoids constitute significant components of the diet and display a diverse array of biological effects (16,19,21,26). Polyphenolic compounds, including a large class of flavonoids, are enriched in certain vegetables, fruits, seeds, and beverages (e.g., tea and wine) and are regarded as a class of semiessential nutrients for humans. Dietary intake rich in these compounds has been suggested to improve the health of individuals and decrease the risk of cardiovascular disease. The beneficial effects of flavonoids have been attributed to their antioxidant and anti-inflammatory properties (18,19,31). The effects of flavonoids, including quercetin, on a variety of inflammatory processes and immune functions have been extensively reviewed (4,6,11,17,25,27,28,40). Tumor necrosis factor alpha (TNF-␣) is one of the major proinflammatory cytokines involved in the pathogenesis of chronic inflammatory diseases and is modulated by oxidative stress (5, 35). TNF-␣ is a multifunctional cytokine that regulates the growth, proliferation, differentiation, and viability of activated leukocytes. TNF-␣ also triggers the cellular release of other cytokines, chemokines, or inflammatory mediators and displays antiviral and antimicrobial effects (1, 2, 39).Numerous signaling cascades have been elucidated in promotion of proinflammatory conditions by proinflammatory cytokines, such as TNF-␣, which involves the activation of inducible transcriptional factors (1,12,13,14,29,39). NF-␤ is one of the principal inducible transcription factors whose modulation triggers a cascade of signaling events involving an integrated sequence of protein-regulated steps, some of which are potential key targets for intervention in treating inflammatory conditions (3,7,20,29,33,34). Previous studies have shown that quercetin inhibits lipopolysaccharide (LPS)-stimulated NF-␤ activation in RAW 264.7 macrophage (8, 37) and also inhibits LPS-induced I␤ phosphorylation in bone marrowderived macrophage (11). Although quercetin exhibits several biological effects, the molecular mechanisms of its anti-inflammatory effects by peripheral blood ...

Quercetin Promotes the Expression of Genes Involved in Phagocytosis in Bovine Neutrophils

“…Those results are consistent with the report that quercetin lowers the level of proinflammatory gene expression as a consequence of oxidative stress and different stimuli (Chuammitri et al, 2015;Valerio et al, 2009). Accordingly, the antiinflammatory action of quercetin on TNF-α is dosedependent manner (Nair et al, 2006).…”

“…This phenomenon may be controlled by the transcription factor NF-κB. Many reports have mentioned that quercetin exerts its modulatory effects by reduction of pro-inflammatory genes through NF-κB inactivation (Boesch-Saadatmandi et al, 2011;Cho et al, 2003;Nair et al, 2006). From previous studies, quercetin inhibits the production of many proinflammatory cytokines, including IL-1β and TNF, the findings from the present work suggest that quercetin may be able to modulate the immune response via the NF-κB pathway.…”

“…Many published works have emphasized that quercetin also exerts its effects by promoting and acting as an antioxidant and anti-inflammation (Boots et al, 2008;Cho et al, 2003;Chuammitri et al, 2017;De Marchi et al, 2009;Nair et al, 2006). In fact, quercetin affects the mRNA gene expressions and associated proteins in the innate immune cells, such as the reduction of the IL-1β mRNA level during inflammation was documented (Valerio et al, 2009).…”

In vitro study of Myristica fragrans seed (Nutmeg) ethanolic extract and quercetin compound as anti-inflammatory agent

“…47 Recent research also confirmed that quercetin as one of active compound from M. fragrans can inhibit various cytokines including TNF-α, IL-6, and IL-1β. 15,16,31,48,49 NO plays a significant role in host immune defense, vascular regulation, neurotransmission, and other system in normal condition. Overproduction of inducible NO Synthase (iNOS) is especially related to various human diseases including inflammation.…”

“…Quercetin, the most commonly occuring flavonoid is an excellent antioxidant that is also suggested to possess other beneficial activities. 15,16 The aim of this research is to determine anti-inflammatory potential of M. fragrans seed (Nutmeg) ethanolic extract and pure quercetin extract from M. fragrans on LPS stimulated-murine macrophage cell line (RAW 264.7).…”