Protective Effects of Quercetin on Anxiety-Like Symptoms and Neuroinflammation Induced by Lipopolysaccharide in Rats

Bombi Lee,Insop Shim,Hyejung Lee,Mijung Yeom,Dae-Hyun Hahm

doi:10.1155/2020/4892415

Abstract

Recently, neuroinflammation is thought to be one of the important causes of many neuropsychiatric diseases. Quercetin (QUER) is a natural flavonoid, and it is well known that QUER has antioxidative, anti-inflammatory, and neuroprotective effects. In our study, lipopolysaccharide (LPS) was injected into the lateral ventricle of rats to induce anxiety-like behaviors and neuroinflammation, and it was confirmed that chronic administration of QUER could improve anxiety-like symptoms. We also investigated the effects of QUER on inflammatory markers and its major mechanisms associated with inflammation in the hippocampus. Daily administration of QUER (10, 50, and 100 mg/kg) daily for 21 days significantly improved anxiety-like behaviors in the elevated plus-maze test and open field test. QUER administration significantly reduced inflammatory markers such as interleukin-6, interleukin-1β, cyclooxygenase-2, and nuclear factor-kappaB levels in the brain. In addition, QUER significantly increased the brain-derived neurotrophic factor (BDNF) mRNA level and decreased the nitric oxide synthase (iNOS) mRNA level. Therefore, our results have shown that QUER can improve anxiety-like behaviors caused by chronic neuroinflammation. This anxiolytic effect of QUER has been shown to be due to its anti-inflammatory effects and appropriate regulation of BDNF and iNOS expression. Thus, QUER provides the potential as a therapeutic agent to inhibit anxiety-like symptoms in neuropsychiatric diseases, such as anxiety.

Highlights

Neuroinflammation is thought to be responsible for multiple psychiatric disorders, such as anxiety, depression, schizophrenia, Alzheimer’s disease, and epilepsy in the central nervous system (CNS) [1]. e immune system is infected as age progresses [2, 3]
LPS injection stimulates inflammatory cytokine through the Toll-like receptor 4 (TLR4), which leads to the activation of many inflammatory factors, such as IL-6, IL-1β, and the nuclear factor-kappaB (NF-κB) system [10]
In the elevated plus-maze (EPM) test, QUER has an anxiolytic effect on LPS-related psychological symptoms, such as anxiety, and our results indicate that QUER may inhibit anxiety-like manifestations due to neuroinflammation

Summary

Introduction

Neuroinflammation is thought to be responsible for multiple psychiatric disorders, such as anxiety, depression, schizophrenia, Alzheimer’s disease, and epilepsy in the central nervous system (CNS) [1]. e immune system is infected as age progresses [2, 3]. According to various epidemiological studies, neuroinflammation is a major risk factor, and the relation between systemic inflammation and the cause of neuropsychiatric disorders has been reported [1]. E researchers have led to the hypothesis that QUER may be effective for mitigating LPS-induced neuropsychiatric symptoms, including anxiety. E study investigated the anti-inflammatory effects of QUER. E elevated plus-maze (EPM) test and the open field test (OFT) were performed in order to assess its effects on anxiety-like behaviors impeded by LPS-induced chronic inflammation in rats. We studied the mechanisms of the QUER effect in neural damage and molecular neurobiological control of neuronal inflammation. LPS-stimulated inflammatory cytokine cascades have often been used to study the neurobiological mechanisms of anxiety-like behaviors caused by inflammatory mediators and to develop targeted therapies for neuroinflammation in animal models

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Results

Conclusion