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Background: Smoking is associated with dysregulation of the antioxidant system and addiction., Aim: This study sought to ascertain the effect of Nigella Sativa (NS) oil on the antioxidant system, nicotine/tobacco addiction as well as the expressions of α4β2 nicotinic (nAChR) and dopamine type-2 (DRD2) receptors in selected brain regions of the rat., Methods: Thirty male Sprague-Dawley rats were divided into 6 groups comprising of vehicle-treated control, NS oil only, Smoke only, Smoke + NS oil, Nicotine only and Nicotine + NS oil. Animals were passively exposed to cigarette smoke or nicotine vapour for 12 weeks, however, NS oil treatment commenced from 9th-12th week of the experimental duration., Results: Nicotine vapour and cigarette smoke-induced increase in cotinine level were significantly ameliorated by NS treatment. Cigarette smoke or nicotine vapour exposure significantly (p<0.05) decreased the level of antioxidant enzymes while increasing malondialdehyde level in the brain homogenates of the rats.  Administration of NS oil significantly (p<0.05) reversed the reduced antioxidant level. Cigarette-smoke also significantly increased α4-nAChR expression in the frontal cortex and olfactory bulb compared to control. Nicotine vapour significantly increased DRD2 expression only in the olfactory cortex. NS oil administration reduced both the cigarette-smoke-induced increase in α4-nAChR and nicotine vapour-induced increase in DRD2 gene expression only in the olfactory cortex., Conclusion: Findings from this study suggest that NS oil improves brain antioxidant status while ameliorating nicotine vapour and cigarette smoke addiction through down-regulation of α4-nAChR and DRD2 gene expressions in discrete brain regions in Sprague-Dawley rats.

Decline in cholinergic function and oxidative/nitrosative stress play a central role in Alzheimer's disease (AD). Previous quantitative HPLC profiling analysis has revealed the presence of Pinostrobin, formononetin, vitexin and other neuroprotective flavonoids in Cajanus cajan seed extract. This study was designed to investigate the protective action of Cajanus cajan ethanol seed extract (CC) on learning and memory functions using scopolamine mouse model of amnesia. Materials and methods: Adult mice were pretreated with CC (50, 100, or 200mg/kg, p.o) or vehicle (10ml/kg, p.o) for 16 days consecutively. Scopolamine, a competitive muscarinic cholinergic receptor antagonist (1mg/kg, i.p.) was given an hour after CC pretreatment from days 3 to 16.  The mice were subjected to behavioural tests from day 11 (open field test (OFT)/ Y-maze test (YMT) and Morris water maze task (MWM) from days 12-16. Animals were euthanized 1h after behavioral test on day 16 and discrete brain regions isolated for markers of oxidative stress and cholinergic signaling. Molecular docking analysis was undertaken to predict the possible mechanism(s) of CC-induced anti-amnesic action.  pre-administration of CC significantly reversed working memory and learning deficits caused by scopolamine in YMT and MWM tests, respectively. Moreover, CC prevented scopolamine-induced oxidative and nitrosative stress radicals in the hippocampus evidenced in significant increase in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities with a marked decrease in malondialdehyde (MDA) production, as well as significant inhibition of hippocampal scopolamine-induced increase in acetylcholinesterase activity by CC. The molecular docking analysis showed that out of the 19 compounds, the following had the highest binding affinity; Pinostrobin (-8.7 Kcal/mol), friedeline (-7.5kCal/mol), and lupeol (-8.2 Kcal/mol), respectively, to neuronal muscarinic M1 acetylcholine receptor, α7 nicotinic acetylcholine receptor and amyloid beta peptide binding pockets, which further supports the ability of CC to enhance neuronal cholinergic signaling and possible inhibition of amyloid beta aggregation. This study showed that Cajanus cajan seeds extract improved working memory and learning through enhancement of cholinergic signaling, antioxidant capacity and reduction in amyloidogenesis.

Parkinson's disease (PD) and dementia with Lewy bodies have several commonalities including neurochemical, morphological and clinical features as well as widespread of cortical and limbic α-synuclein and amyloid-β pathologies. Thus, we evaluated the action of hesperidin on α-synuclein and amyloid-β-induced neurodegeneration in Drosophila melanogaster. The disease causing human Aβ peptide or α- synuclein was expressed respectively, in Elav-GAL4 (pan-neuronally) and dopaminergic neurons (ddc-GAL4) using the UAS-GAL4 system. Flies were either grown on food media supplemented with or without hesperidin (HSD) (1, 5, or 10mM). Behavioral assays were carried to investigate the effect of treatment on fecundity, larval motility, climbing ability and lifespan. Aβ>Elav or α-syn>DDC caused significant decrease in fecundity, larva contraction, motility, survival rate, and climbing activities in flies indicative of neurodegeneration. However, supplementation of flies' media with hesperidin (1mM, 5mM and 10mM) showed a dose-dependent increase in the number of line crosses in the egg laying, larva motility, climbing activity in comparison with flies grown on food media only. Conversely, supplementation of fly feed with HSD caused no significant change in lifespan. Findings from this experiment showed that hesperidin could be a potential neuroprotective agent in the amelioration of PD and AD pathogenesis.

Vinpocetine has been shown to protect against degenerative senile cerebral dysfunction via enhancement of cerebral blood flow, cognition and neuroprotective action. This study sought to investigate the protective effect of vinpocetine against haloperidol-induced catalepsy in mice. Vinpocetine (5, 10 or 20 mg/kg, p.o.) was administered 1 h after haloperidol injection for 21 consecutive days. Effect on motor coordination, depressive-like behaviour and working memory were assessed with rotarod, forced swim (FST) and Y-maze tests, respectively. Brains were collected on day 21 for biochemical estimation of nitrosative and oxidative stress parameters. Vinpocetine (10 or 20 mg/kg, p.o.) significantly reversed haloperidol-induced motor deficit in rotarod test and open field test and reduced the duration of catalepsy during acute and chronic catalepsy tests as compared to trihexylphenidyl but failed to reverse haloperidol-induced memory deficit in the Y-maze test. Haloperidol-induced increase in malondialdehyde and nitrite generation as well as deficits in antioxidant enzymes activities were attenuated by chronic administration of vinpocetine. These findings suggest that vinpocetine protects against haloperidol-induced catalepsy and motor deficits through attenuation of oxidative/nitrosative stress.

The leaves of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) is used in Traditional African medicine for the treatment of various ailments including arthritis. The present study sought to investigate the antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (HeCA). HeCA (100, 200 or 400 mg/kg, p.o.) was administered 1 h before intraplantar injection of formalin 1%v/v in saline to evaluate antinociceptive effect. Moreover, its possible mechanism of antinociceptive action was investigated through pretreatment of mice with antagonists of receptors implicated in nociception. Anti¬inflammatory effect of the extract was investigated using the carrageenan-induced paw oedema and complete Freund's adjuvant (CFA)-induced arthritis models in rats. HeCA (400 mg/kg) treatment significantly reduced the duration of paw licking/biting during both in the early (42.12%) and late (75.79%) phases of formalin-induced nociception. However, the antinociceptive effect elicited by HeCA was reverse by pretreatment of mice with naloxone, prazosin, yohimbine, ketanserin, L-arginine, and parachlorophenylalanine (PCPA). HeCA produced dose-dependent and time course decrease in carrageenan-induced paw oedema. Pre- and post-treatment of rats with HeCA ameliorated CFA-induced arthritis evidenced in the significant decrease in arthritic index comparatively similar to the effect of celecoxib. CFA- induced oxidative and nitrosative stress were attenuated by subchronic treatment with HeCA. Findings from this study shows that C. anisata possesses antinociceptive activity through possible interaction with opioidergic, noradrenergic, L-arginine-nitric oxide and serotonergic pathways as well as anti-arthritic property which could be attributed to its ability to prevent the release of inflammatory mediators and oxidative stress.