Neuroprotective Effect of Quercetin Against the Detrimental Effects of LPS in the Adult Mouse Brain

Abstract

Chronic neuroinflammation is responsible for multiple neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Lipopolysaccharide (LPS) is an essential component of the gram-negative bacterial cell wall and acts as a potent stimulator of neuroinflammation that mediates neurodegeneration. Quercetin is a natural flavonoid that is abundantly found in fruits and vegetables and has been shown to possess multiple forms of desirable biological activity including anti-inflammatory and antioxidant properties. This study aimed to evaluate the neuroprotective effect of quercetin against the detrimental effects of LPS, such as neuroinflammation-mediated neurodegeneration and synaptic/memory dysfunction, in adult mice. LPS [0.25 mg/kg/day, intraperitoneally (I.P.) injections for 1 week]-induced glial activation causes the secretion of cytokines/chemokines and other inflammatory mediators, which further activate the mitochondrial apoptotic pathway and neuronal degeneration. Compared to LPS alone, quercetin (30 mg/kg/day, I.P.) for 2 weeks (1 week prior to the LPS and 1 week cotreated with LPS) significantly reduced activated gliosis and various inflammatory markers and prevented neuroinflammation in the cortex and hippocampus of adult mice. Furthermore, quercetin rescued the mitochondrial apoptotic pathway and neuronal degeneration by regulating Bax/Bcl2, and decreasing activated cytochrome c, caspase-3 activity and cleaving PARP-1 in the cortical and hippocampal regions of the mouse brain. The quercetin treatment significantly reversed the LPS-induced synaptic loss in the cortex and hippocampus of the adult mouse brain and improved the memory performance of the LPS-treated mice. In summary, our results demonstrate that natural flavonoids such as quercetin can be beneficial against LPS-induced neurotoxicity in adult mice.

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

“…In our study, we found that the NLRP3 pathway is activated in the brain of db/db mice and that synapses and trophic factors are significantly reduced. This effect of quercetin on neuroinflammation is based on previous studies …”

“…This effect of quercetin on neuroinflammation is based on previous studies. [62][63][64][65] SIRT1 regulates intracellular signalling molecules, inhibits apoptosis, regulates inflammation and resists oxidative stress. 66,67 SIRT1 can be involved in regulating the formation of Alzheimer's disease amyloid and maintaining the stability of the neuronal genome.…”

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

“…The MWM test was used for the evaluation of spatial learning and memory [40,41]. The experimental apparatus consisted of a black circular plastic pool (diameter = 100 cm) located in the center of the room and filled with water (temperature 23 ± 1 • C, depth 40 cm).…”

Neuromodulatory Activity of Dietary Phenolics Derived from Corchorus olitorius L.

“…Thus, their presence in Co extract could contribute to its potential protective role against neuroinflammation‐mediated neurodegeneration. Interestingly, quercetin has been recently assessed in the same LPS mouse model used in our study, where it improved the memory function, protected against LPS‐induced synaptic dysfunction, attenuated the activation of microglia and astrocytes, reduced COX‐2 expression, and halted the LPS‐induced activation of TLR4/NF‐κB Pathway (Khan et al., ). These results are in accordance with our findings with respect to the cognitive improvement as well as the attenuation of GFAP and COX‐2 expression under the effect of Co extract.…”

“…Mice that received Co prior to LPS challenge showed an attenuation of the LPS‐induced reactive gliosis, which could be beneficial in the model used. The effect of Co on reactive gliosis has not been previously reported, but other polyphenols have attenuated systemic inflammation‐induced spatial memory impairment via inhibition of astrocyte activation (Chen, Zhang, et al., ), reduced GFAP expression in retinal glial cells in diabetic rats (Duarte et al., ), and decreased astrocyte activation in a similar model of LPS‐induced neuroinflammatory mouse model (Khan et al., ).…”