Journal Article

Quercetin Attenuates Inflammatory Responses in BV-2 Microglial Cells: Role of MAPKs on the Nrf2 Pathway and Induction of Heme Oxygenase-1

Chen, Zihong, Sun, Grace Y., Chuang, Dennis Y., Gu, Zezong, Jasmer, Kimberly J., Hannink, Mark, Simonyi, Agnes

2015

Overview

A large group of flavonoids found in fruits and vegetables have been suggested to elicit health benefits due mainly to their anti-oxidative and anti-inflammatory properties. Recent studies with immune cells have demonstrated inhibition of these inflammatory responses through down-regulation of the pro-inflammatory pathway involving NF-κB and up-regulation of the anti-oxidative pathway involving Nrf2. In the present study, the murine BV-2 microglial cells were used to compare anti-inflammatory activity of quercetin and cyanidin, two flavonoids differing by their alpha, beta keto carbonyl group. Quercetin was 10 folds more potent than cyanidin in inhibition of lipopolysaccharide (LPS)-induced NO production as well as stimulation of Nrf2-induced heme-oxygenase-1 (HO-1) protein expression. In addition, quercetin demonstrated enhanced ability to stimulate HO-1 protein expression when cells were treated with LPS. In an attempt to unveil mechanism(s) for quercetin to enhance Nrf2/HO-1 activity under endotoxic stress, results pointed to an increase in phospho-p38MAPK expression upon addition of quercetin to LPS. In addition, pharmacological inhibitors for phospho-p38MAPK and MEK1/2 for ERK1/2 further showed that these MAPKs target different sites of the Nrf2 pathway that regulates HO-1 expression. However, inhibition of LPS-induced NO by quercetin was not fully reversed by TinPPIX, a specific inhibitor for HO-1 activity. Taken together, results suggest an important role of quercetin to regulate inflammatory responses in microglial cells and its ability to upregulate HO-1 against endotoxic stress through involvement of MAPKs.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Anthocyanins / Anti-inflammatory agents / Biochemistry / Carbonyl compounds / Carbonyl groups / Carbonyls / Cell culture / Cytokines / Enzymes / Flavonoids / Gene Expression Regulation - drug effects / Heme / Heme oxygenase (decyclizing) / Heme Oxygenase-1 - biosynthesis / Heme Oxygenase-1 - metabolism / Homeostasis / Humans / Immune system / Inflammation / Inflammation - chemically induced / Inflammation - drug therapy / Inflammation - metabolism / Inflammation - pathology / Inhibition / Interdisciplinary aspects / Kinases / Lipopolysaccharides / Lipopolysaccharides - toxicity / Macrophages - drug effects / Macrophages - metabolism / Mice / Microglia / Microglia - drug effects / Microglia - metabolism / Microglial cells / Neurosciences / NF-E2-Related Factor 2 - biosynthesis / NF-E2-Related Factor 2 - genetics / NF-E2-Related Factor 2 - metabolism / NF-kappa B - metabolism / NF-κB protein / Nitric Oxide - biosynthesis / Nitric Oxide - metabolism / Oxidative stress / Oxygenase / p38 Mitogen-Activated Protein Kinases - genetics / PCB / Penicillin / Pharmacology / Physiological aspects / Polychlorinated biphenyls / Polyphenols / Proteins / Quercetin / Quercetin - administration & dosage / Rodents / Signal Transduction - drug effects / Toxicology / Vegetables