Anti‑inflammatory effect of quercetin and galangin in LPS‑stimulated RAW264.7 macrophages and DNCB‑induced atopic dermatitis animal models

Abstract

Flavonols are compounds that have been shown to possess potent anti-inflammatory effects in cellular and animal models of inflammation. In the present study, the anti-inflammatory effects and mechanisms of two natural flavonols, quercetin and galangin, in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were investigated. It was identified that quercetin and galangin markedly reduced the production of nitric oxide (NO), inducible NO synthase and interleukin-6, and the nuclear translocation of nuclear factor-κB (NF-κB). In addition, LPS-induced activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun N-terminal kinase (JNK) was suppressed by quercetin and galangin. Taken together, these data implied that NF-κB, Erk1/2 and JNK may be potential molecular targets of quercetin and galangin in an LPS-induced inflammatory response. Subsequently, the effects of oral administration of quercetin or galangin, either alone or in combination, in a 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD) mouse model were investigated. As a result, measurements of ear thickness and the levels of serum immunoglobulin E, and histological analysis revealed that the two flavonols led to a decrease in inflammation, whereas, in combination, they were even more effective. These results suggested that quercetin and galangin may be promising therapeutic agents for AD. Additionally, their combination may be a novel therapeutic strategy for the prevention of AD.

In VitroEvaluation of the Potential Use of Propolis as a Multitarget Therapeutic Product: Physicochemical Properties, Chemical Composition, and Immunomodulatory, Antibacterial, and Anticancer Properties

“…e levels of these proinflammatory cytokines were also significantly decreased by pinocembrin in macrophages (RAW264.7) [17]. In the same RAW264.7 line, the level of IL-6 and TNF-α cytokines was clearly reduced by propolis-derived galangin [18]. In vivo studies showed that propolis administration to C57BL/6 mice for 14 days led to the inhibition in the production of IL-1, IL-6, IL-2, IL-10, and IFN-c by spleen cells [64].…”

“…In vivo, propolis administration to C57BL/6 mice for 14 days led to reduced production of IL-1, IL-6, IL-2, IL-10, and IFN-c by spleen cells [17]. In addition, ethanolic extract of Brazilian propolis reduced the expression of IL-17 in collageninduced arthritis in mice [18]. us, bee propolis and its constituents can be considered as potential natural antiinflammatory agents that act by modulating immune responses.…”

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

“…The red arrows represent endogenous pathways that are inhibited by flavonoids resulting in reduced pain and inflammation. , NF-κB [51] and Nrf2 [52], Quercetin: MAPK [53], NF-κB [53][54][55], AKT [56], Nrf2 [33,54], and NLRP3 [57] and Naringenin: NF-κB [58][59][60] and Nrf2 [59,61,62]. (B) Ion channels expressed by neurons that are targeted by Vitexin, Quercetin, and Naringenin to reduce pain.…”

“…It is an antioxidant flavonoid that presents anti-inflammatory activity by inhibiting pro-inflammatory cytokines in mouse models of colitis [69], periodontitis [70], cancer pain [71], and acute [54] and chronic arthritis [33]. That effect is mainly related to the ability of quercetin in reducing recruitment of neutrophils (myeloperoxidase [MPO] activity [33,69,72]), oxidative stress [33,54,69,73,74], COX-2 in the knee joint (arthritis model) [33], NLRP3 inflammasome activation (inhibition of ASC speck formation and ASC oligomerization) in macrophages [57], p65 NF-κB activation [53,54] and MAP kinases signaling in macrophages [53], p50 NF-κB activation in primary human keratinocytes [55], and TNF-α, IL-1β and IL-6 production in RAW 264.7 cells stimulated by LPS [75]. Recent studies demonstrated that quercetin is able to modulate the neutrophils actin polymerization [76], pro-inflammatory cytokines expression by mast cells [77,78] and monocytes [79,80], dendritic cell activation [81] and maturation [82], and the phenotype M1 to M2 in macrophages [83][84][85][86].…”

Characterization of Major Flavonols in Ramps (Allium tricoccum)

“…Furthermore, quercetin has been shown to act as an anti-inflammatory agent on cultured cells and ex vivo [65]. Also, clinical trials investigating the bioactivity of quercetin on blood pressure and cardiovascular risk reported potential cardioprotective effects.…”