The monoaminergic pathways are involved in the antidepressant-like effect of quercetin.

Quercetin, a plant-derived flavonoid, is an antioxidant and has demonstrated antidepressant and anti-inflammatory activities in several animal models. However, there is scanty information on the underlying mechanisms of its antidepressant property. This present study aimed at assessing the involvement of monoaminergic systems in the antidepressant-like activity of quercetin in experimental animals. Mice received varying doses of quercetin (25, 50 &100 mg/kg daily) and were then subjected to open field test (OPF), despair tests, the reserpine test, and the yohimbine lethality test (YLT). In addition, monoaminergic involvement was investigated by combining quercetin (100 mg/kg) with dopaminergic antagonists (haloperidol and sulpiride), adrenergic blockers (prazosin, propranolol and yohimbine), and serotonergic blockers/inhibitors (metergoline). The results showed that quercetin produced significant anti-immobility effects in the forced swim test (FST) and tail suspension test (TST), suggesting antidepressant activity. In addition, the potentiation of yohimbine lethality by quercetin further indicates its antidepressant-like property. This antidepressant action demonstrated was, however, blocked when quercetin was co-administered with dopaminergic, adrenergic and serotonergic antagonists, suggesting involvement of the monoaminergic system in the antidepressant action of quercetin. Nevertheless, quercetin did not significantly alter the locomotor activity of mice, which implies lack of stimulant effect. Taken together, these outcomes suggest that monoaminergic systems are likely involved in the anti-depressant effect of quercetin in mice.

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-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.

Protective Effects of Morin Hydrate on Acute Stress-Induced Behavioral and Biochemical Alterations in Mice.

INTRODUCTION: As stress affects the brain both physiologically and chemically, researchers try to find novel anti-stress compounds with beneficial therapeutic effects. In this regard, the effect of stress and its modulation by Morin hydrate was studied using different acute models in mice. METHODS: The models employed were anoxic tolerance, swimming endurance, and acute restraint test. Morin hydrate or the vehicle was administered 30 minutes prior to each stress exposure while in the acute restraint test; the animals were pretreated for 7 days with Morin hydrate, vehicle, imipramine, or diazepam before stress exposure. The measured parameters were the onset of convulsion and immobility time in the anoxic tolerance and swimming endurance test, respectively, while in the acute restraint test, the animals were assessed for stress-induced anxiety using the elevated plus maze and depression using the forced swim test. Thereafter blood was withdrawn from the retro-orbital plexus and plasma separated, the brain was also isolated, homogenized, centrifuged, and the supernatant was obtained for biochemical estimation. RESULTS: Morin hydrate (5, 10, 20 mg/kg) produced a significant reduction in immobility time in the swimming endurance test, while significantly increased the anoxic stress tolerance time. Acute restraint stress caused a significant decrease in reduced glutathione levels (which was reversed by Morin hydrate) and increased the level of malondialdehyde, a thiobarbituric acid reactive substance which is an index of oxidative stress and nitrite. These effects were attenuated by Morin hydrate. Also, pretreatment with Morin hydrate attenuates acute restraint stress-associated anxiety and depression, reversed the hyperglycemia evoked by the stressful exposure and normalized serum cholesterol levels. CONCLUSION: These findings suggest that Morin hydrate exhibits anti-stress effects and may be useful in the relief of stress.

Antinociceptive property of Olax subscorpioidea Oliv (Olacaceae) extract in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Olax subscorpioidea is a shrub or tree found in Nigeria, and other parts of Africa. It is used in the management of inflammatory disorder, mental illness, convulsion, pain, and cancer. However, there is dearth of information on scientific basis for its folkloric use in the management of pain. Therefore, the study was designed to investigate the antinociceptive property of the extract of Olax subscorpioidea (EOS) leaves in mice. MATERIALS AND METHODS: Antinociceptive activity of EOS (12.5-50 mg/kg, i.p.) was investigated using acetic acid induced abdominal writhing, tail immersion, hot plate and formalin tests. RESULTS: Extract of Olax subscorpioidea produced significant dose dependent inhibition of writhing frequency [F(4,20)=155.9, p<0.0001] and significant dose dependent inhibition of neurogenic and inflammatory pains [F(4,20)=116.7, p<0.0001; F(4,20)=40.05, p<0.0001]. It also produced a significant dose dependent prolongation of the latent period and reaction times in tail immersion and hot plate tests in mice [F(4,20)=19.49, p<0.0001; F(4,20)=97.95, p<0.0001]. CONCLUSION: Olax subscorpioidea possessed potent analgesic action, mediated centrally and peripherally, thus justifying its use in the management of pain.