Differential Modulation of the Phospholipidome of Proinflammatory Human Macrophages by the Flavonoids Quercetin, Naringin and Naringenin
authors Conde, TA; Mendes, L; Gaspar, VM; Mano, JF; Melo, T; Domingues, MR; Duarte, IF
nationality International
journal MOLECULES
author keywords macrophages; phospholipids; flavonoids; immunomodulation; inflammation; lipidomics; mass spectrometry
keywords INFLAMMATION; POLARIZATION; PHENOTYPE; ACTIVATION; PATHWAY; ROLES
abstract The immunomodulatory activity of flavonoids is increasingly appreciated. Macrophage phospholipids (PLs) play crucial roles in cell-mediated inflammatory responses. However, little is known on how these PLs are affected upon flavonoid treatment. In this work, we have used mass-spectrometry-based lipidomics to characterize the changes in the phospholipidome of proinflammatory human-macrophage-like cells (THP-1-derived and LPS+IFN-gamma-stimulated) incubated with non-cytotoxic concentrations of three flavonoids: quercetin, naringin and naringenin. One hundred forty-seven PL species belonging to various classes were identified, and their relative abundances were determined. Each flavonoid displayed its own unique signature of induced effects. Quercetin produced the strongest impact, acting both on constitutive PLs (phosphatidylcholines, phosphatidylethanolamines and sphingomyelins) and on minor signaling lipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS) species. Conversely, naringin hardly affected structural PLs, producing changes in signaling molecules that were opposite to those seen in quercetin-treated macrophages. In turn, albeit sharing some effects with quercetin, naringenin did not change PI and PS levels and interfered with a set of phosphatidylcholines distinct from those modulated by quercetin. These results demonstrate that flavonoids bioactivity involves profound and specific remodeling of macrophage phospholipidome, paving the way to future studies on the role of cellular phospholipids in flavonoid-mediated immunomodulatory effects.
publisher MDPI
isbn 1420-3049
year published 2020
volume 25
issue 15
digital object identifier (doi) 10.3390/molecules25153460
web of science category Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
subject category Biochemistry & Molecular Biology; Chemistry
unique article identifier WOS:000559112700001
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journal analysis (jcr 2019):
journal impact factor 3.267
5 year journal impact factor 3.589
category normalized journal impact factor percentile 56.714
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