Regulatory Effects of Quercetin on M1/M2 Macrophage Polarization and Oxidative/Antioxidative Balance

• Published in: Nutrients Vol. 14; no. 1; p. 67
• Main Authors: Tsai, Cheng-Fang, Chen, Guan-Wei, Chen, Yen-Chang, Shen, Ching-Kai, Lu, Dah-Yuu, Yang, Liang-Yo, Chen, Jia-Hong, Yeh, Wei-Lan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24-12-2021; MDPI
• Subjects: Adipose tissue; AKT protein; AMP-activated protein kinase; Animal cognition; Animals; Antibodies; Antioxidants; Antioxidants - pharmacology; Arteriosclerosis; Atherosclerosis; Cell Polarity - drug effects; Cell Polarity - physiology; Central nervous system; Chemokines; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cysteine; Cytokines; Dietary supplements; Enzymes; Flavonoids; Gene amplification; Glutamate-cysteine ligase; Heme; Heme Oxygenase-1 - metabolism; Homeostasis; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Inflammatory diseases; Insulin; Insulin resistance; Interleukin 10; Ligands; Lipopolysaccharides - toxicity; macrophage; Macrophage Activation; Macrophages; Macrophages - metabolism; Markers; Mental disorders; Metabolism; Mice; Microglia; Microglia - drug effects; Microglia - metabolism; Morphology; Neurodegeneration; NF-E2-Related Factor 2 - metabolism; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; Oxidative stress; Oxidative Stress - drug effects; Oxidoreductase; Phagocytosis; Polarization; Prostaglandin endoperoxide synthase; quercetin; Quercetin - pharmacology; Quinones; RAW 264.7 Cells; Signal Transduction - drug effects; Statistical analysis; Tumor Necrosis Factor-alpha - metabolism; United States > US; homeostasis; macrophage; quercetin; inflammation; microglia; oxidative stress
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14010067

Macrophage polarization plays essential and diverse roles in most diseases, such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Homeostasis dysfunction in M1/M2 macrophage polarization causes pathological conditions and inflammation. Neuroinflammation is characterized by microglial activation and the concomitant production of pro-inflammatory cytokines, leading to numerous neurodegenerative diseases and psychiatric disorders. Decreased neuroinflammation can be obtained by using natural compounds, including flavonoids, which are known to ameliorate inflammatory responses. Among flavonoids, quercetin possesses multiple pharmacological applications and regulates several biological activities. In the present study, we found that quercetin effectively inhibited the expression of lipocalin-2 in both macrophages and microglial cells stimulated by lipopolysaccharides (LPS). The production of nitric oxide (NO) and expression levels of the pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, were also attenuated by quercetin treatment. Our results also showed that quercetin significantly reduced the expression levels of the M1 markers, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, in the macrophages and microglia. The M1 polarization-associated chemokines, C-C motif chemokine ligand (CCL)-2 and C-X-C motif chemokine ligand (CXCL)-10, were also effectively reduced by the quercetin treatment. In addition, quercetin markedly reduced the production of various reactive oxygen species (ROS) in the microglia. The microglial phagocytic ability induced by the LPS was also effectively reduced by the quercetin treatment. Importantly, the quercetin increased the expression levels of the M2 marker, IL-10, and the endogenous antioxidants, heme oxygenase (HO)-1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase-1 (NQO1). The enhancement of the M2 markers and endogenous antioxidants by quercetin was activated by the AMP-activated protein kinase (AMPK) and Akt signaling pathways. Together, our study reported that the quercetin inhibited the effects of M1 polarization, including neuroinflammatory responses, ROS production, and phagocytosis. Moreover, the quercetin enhanced the M2 macrophage polarization and endogenous antioxidant expression in both macrophages and microglia. Our findings provide valuable information that quercetin may act as a potential drug for the treatment of diseases related to inflammatory disorders in the central nervous system.