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

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.

Neuroprotective and Antioxidant Enhancing Properties of Selective Equisetum Extracts

“…Zhang et al [38] reported that quercetin exerted the beneficial or detrimental effects on the shoaling and anxiety behaviors in zebrafish depending on the treatment concentrations, and the underlying mechanisms are potentially associated with neuroinflammation and neuron apoptosis. Quercetin inhibited anxiety-like symptoms and neuroinflammation induced by lipopolysaccharide in rats as stated by Lee et al [39]. Quercetin mitigated anxiety-like behavior and normalized hypothalamus-pituitary-adrenal axis function in a mouse model of mild traumatic brain injury as reported by Kosari-Nasab et al [40].…”

Association Between Dietary Flavonoids Intake and Cognitive Function in an Italian Cohort

“…Among the compounds found to be associated with better cognitive health in our study, flavonols and flavanones have been shown to increase the transforming growth factor-β1 (TGF-β1) levels [ 42 , 43 ], a neurotrophic factor that exerts a key role in recognition memory formation, and a deficit of TGF-b1 signaling can contribute to cognitive decline in Alzheimer’s disease [ 44 , 45 ]. With special regard to quercetin (a flavonol found related to better cognitive health in our study), it has demonstrated effectiveness in animal models of Alzheimer’s disease in decreasing of oxidative stress [ 46 ] and positively modulating Nrf2/HO-1 (nuclear factor erythroid 2–related factor 2/heme oxygenase-1) pathway [ 47 ]; also, an effect toward neuro-inflammation through regulation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and has been observed [ 48 ]. Furthermore, quercetin has been shown to induce the expression of a brain-derived neurotrophic factor (BDNF) [ 49 ] as well as a nerve growth factor (NGF) [ 50 ], which are the most studied and best-characterized neurotrophins of the central nervous system, involved in the modulation of synaptic plasticity and adult neurogenesis.…”

Cell Clearing Systems as Targets of Polyphenols in Viral Infections: Potential Implications for COVID-19 Pathogenesis

“…Neuroprotective effects of quercetin and kaempferol are widely documented in various experimental models, which are associated, either directly or indirectly, with modulation of autophagy and immunoproteasome pathways. These include reduction of oxidative stress and neuroinflammation, induction of M2 microglia polarization, improvement of BBB function, prevention of AGE/RAGE-related neuronal damage, inhibition of HMBG1/TLR4 axis, and activation of AMPK and Nrf2 [ 200 , 201 , 202 , 203 , 204 , 205 , 206 ]. Both quercetin and kaempferol, through inhibition of cytochrome P-450-dependent catalysis, prevent the hepatic metabolism of 17 beta-estradiol [ 207 ], whose effects are bound to autophagy activity [ 208 ] and are potentially relevant in the frame of either influenza virus or COVID-19 pathogenesis [ 209 , 210 ].…”