Abstract
Plumbagin, a hydroxy-1,4-naphthoquinone, confers neuroprotection via antioxidant and anti-inflammatory properties. The present study aimed to assess the effect of plumbagin on behavioral and memory deficits induced by intrahippocampal administration of Quinolinic acid (QA) in male Wistar rats and reveal the associated mechanisms. QA (300 nM/4 μL in Normal saline) was administered i.c.v. in the hippocampus. QA administration caused depression-like behavior (forced swim test and tail suspension tests), anxiety-like behavior (open field test and elevated plus maze), and elevated anhedonia behavior (sucrose preference test). Furthermore, oxidative–nitrosative stress (increased nitrite content and lipid peroxidation with reduction of GSH), inflammation (increased IL-1β), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were observed in the hippocampus region of QA-treated rats as compared to normal controls. Plumbagin (10 and 20 mg/kg; p.o.) treatment for 21 days significantly ameliorated behavioral and memory deficits in QA-administered rats. Moreover, plumbagin treatment restored the GSH level and reduced the MDA and nitrite level in the hippocampus. Furthermore, QA-induced cholinergic dysfunction and mitochondrial impairment were found to be ameliorated by plumbagin treatment. In conclusion, our results suggested that plumbagin offers a neuroprotective potential that could serve as a promising pharmacological approach to mitigate neurobehavioral changes associated with neurodegeneration.
Highlights
Free radical generation leading to nitro-oxidative stress and neuroinflammation are considered as the major cause of neurobehavioral changes and depression-like behavior [1]
We observed that the ICV-Quinolinic acid (QA)-exposed group shows remarkable (p < 0.001) prolongation of immobility time in comparison with the normal control set
QA + plumbagin-20 mg/kg displayed a noteworthy (p < 0.01) decrease in the immobility time when compared with the ICV-QA-exposed group (Figure 1)
Summary
Free radical generation leading to nitro-oxidative stress and neuroinflammation are considered as the major cause of neurobehavioral changes and depression-like behavior [1]. Neurobehavioral changes are caused primarily by any brain injury that will have a severe impact on a patient’s day-to-day functioning and social involvement, leading to depression [2]. Elevated concentrations of QA in the brain were found to be involved in the pathogenesis of various neuronal diseases including depression, cognitive deficits, Huntington’s disease, and Alzheimer’s disease [6–8]. Administration of QA directly into the brain, enhances Ca2+ influx on binding to NMDA receptors and causes excitotoxic damage to the hippocampus and striatal regions [11]. QA alters mitochondrial function by inducing oxidative damage to mitochondrial DNA and lipids, leading to cell death followed by neurobehavioral changes [14]. Intracerebroventricular (ICV) injection of QA is associated with neurobehavioral changes [15]
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