Quercetin inhibits LPS-induced macrophage migration by suppressing the iNOS/FAK/paxillin pathway and modulating the cytoskeleton

Abstract

The natural flavonoid quercetin has antioxidant, anti-inflammatory, and anticancer effects. We investigated the effect of quercetin on lipopolysaccharide (LPS)-induced macrophage migration. Quercetin significantly attenuated LPS-induced inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production in RAW264.7 cells without affecting their viability. Additionally, quercetin altered the cell size and induced an elongated morphology and enlarged the vacuoles and concentrated nuclei. Quercetin significantly disrupted the F-actin cytoskeleton structure. Furthermore, quercetin strongly inhibited LPS-induced macrophage adhesion and migration in a dose-dependent manner. Moreover, quercetin inhibited the LPS-induced expression of p-FAK, p-paxillin, FAK, and paxillin as well as the cytoskeletal adapter proteins vinculin and Tensin-2. Therefore, quercetin suppresses LPS-induced migration by inhibiting NO production, disrupting the F-actin cytoskeleton, and suppressing the FAK-paxillin pathway. Quercetin may thus have potential as a therapeutic agent for chronic inflammatory diseases.

Blueberry Counteracts BV-2 Microglia Morphological and Functional Switch after LPS Challenge

“…Firstly, these processes require actin cytoskeleton reorganization, which leads to several cellular responses, such as migration. Different compounds are present in the BB extracts obtained by Cui et al (2019), and among them, quercetin, one of the most common flavonoids, was recently shown to interfere in macrophage migration processes induced by LPS. It significantly disrupted the F-actin cytoskeleton structure and promoted changes in the size and shape of the macrophages, affecting the formation of filopodia or lamellipodia, which are supported by actin filaments and associated proteins [62].…”

Quercetin alleviates acute kidney injury by inhibiting ferroptosis

“…Quercetin (QCT), a natural flavonoid which is commonly found in numerous fruits and vegetables, is an indispensable part of the diet. QCT comes into the focus of medicinal interest because of its extensive pharmacological effects, such as anti-cancer, anti-viral, anti-oxidant, anti-inflammatory and anti-senescence effects [10] , [11] , [12] , [13] , [14] . A previous study reported that QCT could selectively kill senescent cells and enhance lifespan in old mice [15] .…”

A Systematic Study of Mechanism of Sargentodoxa cuneata and Patrinia scabiosifolia Against Pelvic Inflammatory Disease With Dampness-Heat Stasis Syndrome via Network Pharmacology Approach

“…The active compounds were chosen based on the previously study and literature mining. As acacetin, kaempferol, quercetin are predicted as active compounds by in silico study, we previously reported that quercetin inhibited LPS induced macrophage migration by inhibiting iNOS/FAK/Paxillin pathway ( Cui et al, 2019 ). Therefore, acacetin, kaempferol are selected for the further validation.…”

“…FAK binds to proteins containing the Src sequence to form FAK/Src complex. Then FAK/Src complex recruits downstream proteins, such as paxillin to participate in the regulation of cell cycle, adhesion, and metastasis ( Cui et al, 2019 ). Our previous study confirmed that quercetin inhibited the iNOS/FAK-paxillin pathway to limit LPS-induced macrophages migration ( Cui et al, 2019 ).…”

“…Then FAK/Src complex recruits downstream proteins, such as paxillin to participate in the regulation of cell cycle, adhesion, and metastasis ( Cui et al, 2019 ). Our previous study confirmed that quercetin inhibited the iNOS/FAK-paxillin pathway to limit LPS-induced macrophages migration ( Cui et al, 2019 ). Moreover, kaempferol could predominantly suppress the invasion and migration of renal cancer cells via the downregulation of AKT and FAK pathways ( Hung et al, 2017 ).…”