Quercetin abrogates lipopolysaccharide-induced depressive-like symptoms by inhibiting neuroinflammation via microglial NLRP3/NFκB/iNOS signaling pathway

Behav Brain Res. 2023 Jul 26:450:114503. doi: 10.1016/j.bbr.2023.114503. Epub 2023 May 18.

Abstract

Background: Major depressive disorder is a serious psychiatric illness having serious damaging effect on the quality of life of suffers. Quercetin is a plant flavonoid, mostly used as a constituent in dietary products. This study evaluated antidepressant effect of quercetin on lipopolysaccharide (LPS)-induced depression in rats.

Materials and methods: Twenty-one male rats were randomly assigned into three groups (n = 7): group 1 (vehicle only), group 2 (quercetin), group 3 (LPS). Rats were treated with vehicle (10 mL/kg, p.o.) or quercetin (50 mg/kg, p.o.) for seven days. Sixty minutes after treatment on day seven, all animals were injected with LPS (0.83 mg/kg, i.p.) except group 1 (vehicle only). Twenty-four hours after LPS injection, animals were assessed for depressive symptoms using forced swim, sucrose splash and open field tests. Animals were sacrificed; brain samples collected for bioassay of pro-inflammatory mediators, TNF-α, IL-6 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA) while expressions of NF-κB, inflammasomes, microglia and iNOS were quantified by immunohistochemistry.

Results: The LPS significantly (p < 0.05) decreased mobility of rats in FST and decreased sucrose preference, which is indicative of depressive-like behaviours. These behaviours were significantly (p < 0.05) attenuated by quercetin compared to control (vehicle only). Following LPS exposure, the expressions of inflammasomes, NF-κB, iNOS, proinflammatory cytokines and microglia positive cells in the hippocampus and prefrontal cortex were significantly (p < 0.05) elevated. All these were attenuated by pretreating animals with quercetin.

Conclusion: Quercetin exhibit antidepressant-like property, which may be related to inhibition of neuroinflammatory signaling pathways.

Keywords: Depression; Microglia; Neuroinflammation; Neuropsychiatry; Proinflammatory cytokine; Quercetin.

MeSH terms

  • Animals
  • Antidepressive Agents / therapeutic use
  • Depression / chemically induced
  • Depression / drug therapy
  • Depression / metabolism
  • Depressive Disorder, Major* / metabolism
  • Inflammasomes / metabolism
  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / pharmacology
  • Microglia
  • NF-kappa B* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Neuroinflammatory Diseases
  • Quality of Life
  • Quercetin / pharmacology
  • Rats
  • Signal Transduction
  • Sucrose / metabolism

Substances

  • NF-kappa B
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Quercetin
  • Inflammasomes
  • Antidepressive Agents
  • Sucrose