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

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-alpha, IL-6 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA) while expressions of NF-kappa B, 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-kappa B, 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 neuro-inflammatory signaling pathways.