Quercetin ameliorates chronic restraint stress- and LPS-induced anxiety-like behaviors by modulating neuroinflammation in the lateral hypothalamus.

Abstract

Objective: Quercetin is a natural flavonoid which has been shown to exhibit anti-inflammatory and anxiolytic properties. Neuroinflammation has recently been identified as a major cause of anxiety disorders. Both the lateral hypothalamus (LH) and bed nucleus of the stria terminalis (BNST) are important brain regions that regulate anxiety. This study aims to explore the effect of quercetin on anxiety-like behaviors, as well as the underlying mechanisms associated with neuroinflammation in the LH and BNST.

Methods: The anxiety models were established in male mice by chronic restraint stress (CRS) and lipopolysaccharide (LPS) administration. The elevated plus maze (EPM) and open field (OF) tests were used to evaluate anxiety level. Immunofluorescent staining and quantitative real-time PCR were performed to examine the expression of microglia and inflammatory cytokines in the LH and BNST of male mice.

Results: Behavioral data showed that quercetin treatment in male mice significantly alleviated anxiety in the EPM and OF tests. Examination of the inflammation level further revealed that quercetin administration significantly inhibited microglia activation in the LH and BNST of CRS- and LPS-treated male mice, while concurrently reducing the levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the LH of CRS-treated male mice, as well as interleukin-1β (IL-1β) mRNA expression in the LH of LPS-treated male mice. Furthermore, we found that the expression of NF-κB was downregulated by quercetin in the LH of CRS-treated male mice.

Conclusion: Our study indicates the clinical potential of quercetin in neuroinflammation-related anxiety, and begins to show that the underlying mechanism in the chronic restraint stress condition may potentially involve the modulation of NF‑κB signaling pathway in the LH.