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Currently, prevailing evidence have identified cholinergic and oxidative pathways as important therapeutic targets for abating ketamine-induced schizophrenia-like behavior. Thus, this study evaluated the ability of hesperidin, a naturally occurring antioxidant and neuroprotective flavonoid, to prevent and reverse ketamine-induced schizophrenia-like behaviors and changes in cholinergic, oxidative and nitrergic status in mice. Forty-eight male Swiss mice were allotted into the preventive and reversal studies with 4 groups (n = 6) each. In the preventive study, groups 1 and 2 received vehicle (10 mL/kg/p.o./day), while groups 3 and 4 had hesperidin (100 mg/kg/p.o./day) for 14 days, but ketamine (20 mg/kg/i.p./day) was concurrently given to groups 2 and 4 from days 8-14. In the reversal study, groups 1 and 3 received vehicle, groups 2 and 4 were pretreated with ketamine for 14 days. Nevertheless, groups 3 and 4 additionally received hesperidin from days 8-14. Thereafter, schizophrenia-like behavior from exploratory activity, open-field (positive symptoms), Y-maze (cognitive symptoms) and social interaction (negative symptoms) tests were evaluated. Brain levels of oxidative/nitrergic (glutathione, superoxide-dismutase, malondialdehyde and nitrite levels) and cholinergic (acetylcholinesterase activity) markers were measured in the prefrontal-cortex, striatum and hippocampus. Hesperidin prevents and reverses ketamine-induced hyperactivities, social withdrawal and cognitive impairment. Also, hesperidin prevented and reversed ketamine-induced decrease in glutathione and superoxide-dismutase levels in the prefrontal-cortical, striatal and hippocampal brain regions in mice. Consequently, hesperidin attenuated ketamine-induced increase in malondialdehyde, nitrite levels and acetylcholinesterase activities in the prefrontal-cortex, striatum and hippocampus, respectively. The study showed that hesperidin prevents and reverses ketamine-induced schizophrenia-like behavior through inhibition of oxidative/nitrergic stress and acetylcholinesterase activity in mice brains. Therefore, these findings suggest that hesperidin dietary supplementation could provide natural nutritional intervention to protect against epigenetic-induced mental ill-health like schizophrenia, and thus serve as an important agent for nutritional psychiatry.

A substantial number of epileptic patients are resistant to the current medication thus necessitating the search for alternative therapies for intractable forms of the disease. Previous studies demonstrated the acute anticonvulsant properties of the methanol extract of the stem bark of Psychotria camptopus (MEPC) in rats. This study investigated the effects of MEPC on pentylenetetrazole-kindled Wistar rats. Kindling was induced by intraperitoneal injection of pentylenetetrazole (37.5 mg/kg) on every alternate day, 1 h after each daily oral pretreatment of rats (8 ≤ n ≤ 10) with MEPC (40, 80 and 120 mg/kg), vehicle or diazepam (3 mg/kg) for 43 days. The kindling development was monitored based on seizure episodes and severity. Rats’ brains were collected on day 43 for the determination of oxidative stress parameters. The histomorphological features and neuronal cell viability of the prefrontal cortex (PFC) and hippocampus were also assessed using H&E and Cresyl violet stains. Chronic administration of pentylenetetrazole time-dependently decreased the latency to myoclonic and generalized seizures, and increased seizure scores and the number of kindled rats. MEPC and diazepam significantly increased the latencies to myoclonic jerks and generalized tonic-clonic seizures. These substances also reduced seizure score and the number of rats with PTZ-kindling. MEPC improved glutathione status and decreased lipid peroxidation in the brains of kindled rats. MEPC also exhibited neuroprotection against pentylenetetrazole-induced hippocampal and PFC neuronal damages. These results suggest that P. camptopus has antiepileptogenic activity, which might be related to the augmentation of antioxidant and neuroprotective defense mechanisms, and further confirm its usefulness in the management of epilepsy.

Cnidoscolus aconitifolius contains various phenolic compounds possessing anti-inflammatory and antioxidant properties. This study aimed to evaluate the protective effect of the Methanol Extract of Cnidoscolus aconitifolius (MECA) against LPS-induced memory impairment, oxidative stress and neuroinflammation in rats. Thirty male Wistar rats were divided into 5 groups (n = 6). Group 1 served as the control and received the vehicle, group 2 was negative control, groups 3–5 received MECA (25, 50, and 100 mg/kg) for 14 days. Groups 2–5 were daily injected with LPS (250 μg/kg, i.p) from day 8–14 of treatment. Memory impairment was evaluated after the last LPS administration using the Y-Maze Test (YMT) and Novel Object Recognition Test (NORT). Brain prefrontal cortex (PFC) and hippocampus (HPC) sections were obtained and levels of reduced glutathione (GSH), malondialdehyde, catalase, nitrite, acetylcholinesterase, and TNF-α and IL-6 were determined. Oral administration of MECA significantly reversed LPS-induced memory impairment in the YMT and NORT. MECA significantly reduced LPS-induced elevated malondialdehyde and nitrite, while preventing depletion of GSH and catalase in the PFC and HPC sections of the brain. Acetylcholinesterase activity is also reduced. MECA (100 mg/kg) significantly reduced IL-6 and TNF-α levels in PFC and HPC of LPS-treated rats. This study showed that the methanol extract of Cnidoscolus aconitifolius has significant protective effect against lipopolysaccharide-induced memory impairment via mechanisms related to inhibition of neuroinflammation and oxidative stress.

Neuroimmune alterations have important implication in the neuropsychiatric symptoms and biochemical changes associated with lead-induced neurotoxicity. It has been suggested that inhibition of neuroinflammatory-mediated lead-induced neurotoxicity by phytochemicals enriched with antioxidant activities would attenuate the deleterious effects caused by lead. Hence, this study investigated the neuroinflammatory mechanism behind the effect of Ginkgo biloba supplement (GB-S) in lead-induced neurotoxicity in mice brains. Mice were intraperitoneally pretreated with lead acetate (100 mg/kg) for 30 min prior the administration of GB-S (10 and 20 mg/kg, i.p.) and ethylenediaminetetraacetic acid (EDTA) (50 mg/kg, i.p.) for 14 consecutive days. Symptoms of neurobehavioral impairment were evaluated using open field test (OFT), elevated plus maze (EPM), and tail suspension test (TST) respectively. Thereafter, mice brain hippocampi were sectioned for myeloperoxidase activity (MPO), pro-inflammatory cytokine (TNF-α and IL-6) estimation and inflammatory protein (NF-κB) expression. Furthermore, histomorphormetric studies (Golgi impregnation and Cresyl violet stainings) were carried out. GB-S (10 and 20 mg/kg) significantly restores neurobehavioral impairments based on improved locomotion, reduced anxiety- and depressive-like behavior. Moreover, GB-S reduced the MPO activity, inhibits TNF-α, IL-6 release, and downregulates NF-κB immunopositive cell expression in mice hippocampus. Histomorphometrically, GB-S also prevents the loss of pyramidal neuron in the hippocampus. The endpoint of this findings suggest that GB-S decreases neuropsychiatric symptoms induced by lead acetate through mechanisms related to inhibition of release of pro-inflammatory mediators and suppression of hippocampal pyramidal neuron degeneration in mice.

Oxidative and inflammatory signaling pathways have been identified as important targets for mitigating hypoxic stress-induced neurological complications. Thus, the effects of naringenin, a potent antioxidant, anti-inflammatory and neuroprotective bioflavonoid on hypoxic stress-induced depressive-like and anxiety-related behaviors in mice, and the underlying molecular mechanisms were evaluated in this study. Thirty-five male Swiss mice were distributed into 5 groups (n = 7). Mice in group I (non-stress control) and group 2 (stress-control) both had vehicle (5 % DMSO), while groups 3-5 received naringenin (10, 25 and 50 mg/kg), intraperitonally. Thirty minutes later, mice in groups 2-5 were subjected to 15 min hypoxic stress, daily for 14 days. Locomotor activity, anxiety and depression were evaluated on day 15. The mice brains were processed for malondialdehyde, glutathione, superoxide-dismutase (SOD), catalase, tumor necrosis factor-alpha (TNF-α) and interleukin-1β assays. The serum corticosterone concentration and expressions of the brain immunopositive cells of inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-kB) and brain derived neurotrophic factor (BDNF) as well as histomorphological changes of the amygdala were also determined. Naringenin (25-50 mg/kg) ameliorated the hypolocomotion, depressive- and anxiety-like behaviors in hypoxic mice. The increased brain contents of malondialdehyde, TNF-α, interleukin-1β, and decreased antioxidant (glutathione and SOD) status were attenuated by naringenin. Naringenin (10 mg/kg) increases BDNF expression but did not significantly (p 0.05) alter corticosterone and catalase contents. The increased expressions of iNOS and NF-kB as well as loss of amygdala neuronal cells were reduced by naringenin (10 mg/kg). Overall, these findings suggest that naringenin improves depressive- and anxiety-like behaviors in mice exposed to hypoxic stress by modulating oxido-inflammatory insults and NF-kB/BDNF expressions.

Mounting evidences have shown that nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox-2) pathway modifies glutamic-acid decarboxylase-67 (GAD67) (GABAergic enzyme) and cholinergic systems via oxidative-nitrergic mechanisms in schizophrenia pathology. Rutin, a neuroactive antioxidant compound, with proven neuroprotective property has been shown to reduce schizophrenic-like behavior in mice. This study sought to investigate the mechanisms of action of the psychopharmacological activity of rutin in the preventive and reversal effects of ketamine-induced schizophrenic-like behavior, oxidative-nitrergic stress, cholinergic and GABAergic derangements in mice. In the preventive treatment, male mice were given rutin (0.1, 0.2 and 0.4 mg/kg) or risperidone (0.5 mg/kg) orally for 14 days prior to ketamine (20 mg/kg, i.p.) treatment from the 8 to 14th day. However, in the reversal treatment, ketamine was given for 14 days prior to rutin and risperidone. Behavioral (open-field, social-interaction and Y-maze tests), biochemical (oxidative/nitrergic stress markers, acetylcholinesterase activity), immunohistochemical (GAD67, Nox-2) and neuronal cell deaths in the striatum, prefrontal cortex, and hippocampus were evaluated. Ketamine-induced behavioral impairments were prevented and reversed by rutin. Exposure of mice to ketamine increased malondialdehyde, nitrite contents, acetylcholinesterase activity, neuronal cell death and Nox-2 expressions in the striatum, prefrontal cortex and hippocampus. Conversely, these derangements were prevented and reversed by rutin. The decreased glutathione levels due to ketamine were marked increased by rutin. Rutin only prevented ketamine-induced decrease in GAD67 expression in the striatal-hippocampal region. Altogether, the study showed that the prevention and reversal treatments of mice with rutin attenuated ketamine-induced schizophrenic-like behaviors via reduction of Nox-2 expression, oxidative/nitrergic stresses, acetylcholinesterase activity, and increased GAD67 enzyme.

This study investigated the effect of high doses of monosodium glutamate (MSG), a known food additive on hepatic, memory and locomotor functions in mice, and the ameliorative potentials of Jobelyn® (JB), a unique dietary supplement. Twenty four male Swiss mice divided into 4 groups (n = 6) were given MSG (2, 4 and 8 g/kg) or normal saline (10 mL/kg) orally for 14 days. In the intervention study, another set of 30 male Swiss mice distributed into 5 groups (n = 6) received normal saline, MSG (8 g/kg) alone or in combination with JB (5, 10 and 20 mg/kg) orally, for 14 days. Memory and locomotor functions as well as brain oxido-nitrergic stress biomarkers were then assessed in both studies. The hepatic oxido-nitrergic stress biomarkers, liver enzymes functions and histomorphology of the liver were also assessed. MSG (2, 4 and 8 g/kg) produced memory dysfunction, hyperlocomotion, increased malondialdehyde and nitrite levels accompanied by decreased antioxidant status in the brain and hepatic tissues. MSG-treated mice had increased hepatic enzyme activities (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) and distorted cyto-architectural integrity of the liver. These findings further suggest that MSG compromised hepatic functioning, which might also contribute to its neurotoxicity. However, JB (5, 10 and 20 mg/kg, p.o) attenuated the memory deficit, hyperlocomotion, increased oxido-nitrergic stress responses in the brain and hepatic tissues induced by MSG (8 g/kg, p.o). JB also normalized hepatic enzymes activities and histomorphological changes in MSG-treated mice. Taken together, JB mitigated MSG-induced toxicity through mechanisms relating to enhancement of cellular antioxidant-machineries and normalization of hepatic enzymatic functions.

Adaptogens are substances that act nonspecifically to combat stress by regulating the key elements involved in stress-induced pathologies. D-Ribose-L-cysteine (DRLC), a potent glutathione (GSH) booster, has been recommended for relief of stress. Hence, we investigated its adaptogenic-like effect in mice subjugated to unpredictable chronic mild stress (UCMS). Thirty six male Swiss mice were assigned to 6 groups (n = 6): group 1 received saline (p.o, non-stress control), group 2 (stress-control) also had saline, groups 3 to 5 received DRLC (25, 50 and 100 mg/kg, p.o) whereas group 6 had ginseng (50 mg/kg, p.o). The animals in groups 2-6 were subjugated to UCMS 30 min later, daily for 21 days and afterwards, tested for memory and anxiety. Blood glucose, serum corticosterone concentrations and adrenal weight were determined. The brain tissues were processed for estimation of malondialdehyde (MDA), GSH, superoxide-dismutase (SOD), catalase, tumor necrosis factor-alpha (TNF-α), interleukin-6, acetyl-cholinesterase, and caspase-3 activities. The histomorphologic features and neuronal viability of the hippocampus, amygdala and prefrontal cortex were also determined. DRLC (25-100 mg/kg) reduces anxiety, memory deficit, adrenal gland enlargement, glucose, and corticosterone concentrations in UCMS-mice. The increased brain contents of MDA, TNF-α, interleukin-6, acetyl-cholinesterase and decreased antioxidant (GSH, SOD and catalase) status induced by UCMS were attenuated by DRLC. The DRLC increased caspase-3 activity and reduces histomorphological distortions of neuronal cells of the hippocampus, amygdala and prefrontal cortex of stressed-mice. These findings suggest that DRLC has adaptogenic-like effect which might be related to modulation of corticosterone-mediated oxido-inflammatory processes and altered caspase-3 activity.

Phragmanthera incana (Schum) is a specie of mistletoe that has been mentioned in Nigeria ethnomedicine to be used in the treatment of inflammatory disorders. The aim of this study was to investigate the anti-inflammatory effect of Phragmanthera incana leaf ethanol extract (PIEE) in carrageenan-induced inflammation models in rats. In the carrageenan-induced rat paw oedema experiment, 0.1 mL of carrageenan (1%) was injected into the paw one hour after treatment with PIEE (125, 250 and 500 mg/kg). Paw volume was measured hourly for 4 h using the plethysmometer. The anti-inflammatory activity was investigated using the carrageenan-induced air pouch inflammation model. Leucocytes migration and pro-inflammatory mediators (TNF-α and IL-6) were evaluated in the air pouch exudate. Oxidative stress biomarkers (MDA, Nitrite, GSH and Catalase) were estimated in both the carrageenan-induced paw tissue homogenates and air pouch exudate. PIEE (125, 250 and 500 mg/kg) administration significantly (p

Objective Psychosocial stress has been implicated in the genesis of psychiatric disorders such as memory deficits, depression, anxiety and addiction. Aqueous leaf extract of Cymbopogon citratus (CYC) otherwise known as lemongrass tea has antidepressant, anxiolytic and anti-amnesic effects in rodents. This study was designed to evaluate if C. citratus could reverse the neurobehavioral and biochemical derangements induced by social defeat stress (SDS) in the resident/intruder paradigm. Methods Intruder male mice were divided into five groups (n = 7): group 1 received saline (10 mL/kg, p.o.; non-stress control), group 2 also received saline (10 mL/kg, p.o.; SDS control) while groups 3–5 had C. citratus (50, 100 and 200 mg/kg, p.o.) daily for 14 d. The SDS was carried out 30 min after each treatment from day 7 to day 14 by exposing each intruder mouse in groups 2–5 to a 10 min confrontation in the home cage of an aggressive resident counterpart. The neurobehavioral features (spontaneous motor activity-SMA, anxiety, memory, social avoidance and depression were then evaluated. The concentrations of nitrite, malondialdehyde and glutathione as well as acetylcholinesterase activity in the brain tissues were also determined. Results C. citratus (50, 100 and 200 mg/kg) attenuated hypolocomotion, heightened anxiety, depressive-like symptom, memory deficit and social avoidance induced by SDS. The altered levels of oxidative stress and acetyl-cholinesterase in SDS-mice were positively modulated by C. citratus. Conclusion The results of this study suggest that C. citratus might mitigate psychosocial stress-induced neurologic diseases in susceptible individuals.

Objectives Blend of seeds and leaves of Picralima nitida herein referred to as West African Durand powder (WDP) was investigated for antinociceptive and anti-inflammatory properties. Methods Acute toxic effect of the aqueous extract was evaluated in mice of both sexes. Antinociceptive effect of WDP (100–400 mg/kg) was evaluated in models of acetic acid-induced writhing and thermal nociception on hot plate in mice. Carrageenan-induced paw oedema and air pouch rat models were used to evaluate the anti-inflammatory activity of the extract. Results WDP (2,000 mg/kg) showed no toxic effect in mice. WDP at 100, 200 and 400 mg/kg inhibited abdominal writhings by 59.9, 66.0 and 79.0%, respectively. There was a significant increase in reaction time on the hot plate tests in mice treated with WDP (400 mg/kg). The paw oedema was reduced by WDP (100, 200 and 400 mg/kg) 5 h post-carrageeenan. Exudate volume was significantly reduced to 39.8 and 44.8% by 200 and 400 mg/kg WDP, respectively. WDP reduced Leucocytes counts (23.3 and 57.1%, respectively) and neutrophil counts (28.1 and 60.0%, as well as reduced nitrites, malondialdehyde levels and increased glutathione concentrations in the air pouch. Conclusions These results suggest that aqueous extract of blend of seeds and leaves of P. nitida possesses antinociceptive and anti-inflammatory properties.

The effect of ethanol fruit extract of Spondias mombin (FESM) against scopolamine-induced memory impairment was evaluated in mice. Swiss mice were injected with scopolamine (3 mg kg−1, i.p) and tre...

Chrysophyllum abidum fruit is a seasonal fruit commonly eaten as snacks with abundant health promoting phytochemicals in the fruit peels. The fruit peels have been reported to be rich in anti-inflammatory eleagnine, myricetin rhamnoside, quercetin, linoleic acid and oleic acid. We hypothesized that the anti-inflammatory effect of the peel extract involve suppression of pro-inflammatory cytokines, cyclooxygenase-2 and nuclear factor-kappa B (NF-κB). Hence, this study was designed to assess the anti-nociceptive and anti-inflammatory effects of fruit peel extract of Chrysophyllum albidum in animal models of nociception and inflammation. The anti-nociceptive activity of CAPEE (100 and 400 mg/kg) was evaluated in acetic acid-induced writhing and formalin-induced paw licking in mice. Formalin-induced paw edema and carrageenan-induced air pouch models of inflammation were used to evaluate the anti-inflammatory activity. CAPEE (100 and 400 mg/kg) significantly reduced abdominal writhing and paw licking in acetic acid and formalin tests in mice, respectively. CAPEE demonstrated significant inhibition of paw edema at 24 h (41.0% and 55.7%) and 72 h (52.3% and 86.6%) after formalin injection. CAPEE suppressed inflammatory responses in carrageenan-induced air pouch by reducing exudates, inflammatory cells infiltration, nitrites and myeloperoxidase activity. There was significant inhibition of tumor necrosis factor-alpha, interleukin-6 levels and reduced immunopositive expression of COX-2 and NF-κB. In conclusion, CAPEE has anti-nociceptive and anti-inflammatory potentials via mechanisms associated with inhibition of pro-inflammatory cytokines and cyclooxygenase-2 (COX-2) expression through suppression of nuclear factor kappa B (NF-κB) activation, and has potential as a functional food ingredient.

d-Ribose-l-cysteine (DRLC) is an analogue of cysteine that has been shown to boost cellular antioxidant capacity by enhancing intracellular biosynthesis of glutathione (GSH). Deficiency of GSH has been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with loss of memory. Thus, the use of antioxidants to prevent or retard the progression of memory deteriorations in persons with AD has been the focus of intense investigations. This study was carried out to evaluate the effects of DRLC on memory and scopolamine-induced amnesia, acetyl-cholinesterase activity, and oxidative stress in mice. Male Swiss mice were given oral administration of saline (10 ml/kg), DRLC (25, 50, and 100 mg/kg) or donepezil (1 mg/kg) 30 min before testing for memory performance using Y-maze and object recognition models. Another set of mice were also pretreated orally with saline, DRLC (25, 50, and 100 mg/kg) or donepezil (1 mg/kg) but in combination with scopolamine (3 mg/kg, i.p.) daily for 7 days. Thirty minutes after treatment on Day 7, memory function was then evaluated. The brain levels of acetyl-cholinesterase and oxidative stress parameters were assayed. DRLC significantly (p < .05) enhanced memory performance and attenuated scopolamine-induced amnesia. Increased acetyl-cholinesterase activity and oxidative stress, as shown by decreased antioxidant substrates (glutathione and catalase) and elevated malondialdehyde contents in mice with scopolamine amnesia were also attenuated by DRLC. Our findings suggest that inhibition of oxidative stress and acetyl-cholinesterase activity might contribute to the potential benefit of DRLC in persons with amnesia.

Oxidative stress and neuroinflammation play key roles in the initiation and progression of Parkinson's disease (PD), a neurodegenerative disorder, associated with the loss of nigrostriatal dopaminergic pathway. Thus, compounds that can mitigate oxidative stress and neuroinflammation are being investigated as promising agents for the treatment of PD. This study was designed to evaluate the effects of methyl jasmonate (MJ), a potent antioxidant and anti-inflammatory compound on parkinsonian-like symptoms and the underlying biochemical changes induced by rotenone (Rot) in mice. To this end, the effects of graded doses of MJ (25, 50 and100 mg/kg, i.p.) on motor dysfunctions, cognitive and depressive-like disorders induced by Rot (2.5 mg/kg, i.p.) were evaluated. The specific brain regions (striatum, prefrontal cortex and hippocampus) of the animals were processed for various biochemical studies. Rot-treated mice showed reduced motor activity, postural instability, cognitive and depressive-like disorders. Rot also increased brain levels of malondialdehyde (MDA), nitrite, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and acetyl-cholinesterase (AChE) activity. Moreover, Rot reduced the concentration of glutathione (GSH) and increased immnopositive cells of NF-κB and α-synuclein expressions in these brain regions. However, pretreatment with MJ, attenuated the parkinsonian-like symptoms and reduced the brain levels of MDA/nitrite, TNF-α and IL-6 induced by Rot. MJ also reduced AChE activity and down-regulate the expressions of NF-κB and α-synuclein in the brain of Rot-treated mice. These findings suggest that MJ has anti-parkinsonian-like activity, which may be related to the inhibition of oxidative stress, release of pro-inflammatory cytokines, and down regulation of NF-κB and α-synuclein expressions.

Decreased tyrosine hydroxylase (TH) activity, due to degeneration of dopaminergic neurons contributes to the low dopamine content and the motor deficits that characterized Parkinson’s disease (PD). This study examines the effect of methyl jasmonate (MJ), a neuroprotective bioactive compound isolated from jasminum grandiflorum, on motor functions, immunopositive cells of TH, dendritic neurons and dopamine contents in rotenone (Rot)-treated rats. Rats pretreated daily with MJ (100 mg/kg, i.p) for 21 days also received Rot (2.5 mg/kg, i.p.) 30 min after each pretreatment for every 48 h for 21 days. Motor functions were assessed on day 22. The specific brain regions of the rats were processed for determination of dopamine contents, immunopositive cells of TH, neuronal cell morphology and dendritic aborizations. Rot impaired locomotion and rearing behavior, and decreased dopamine content in the striatum, prefrontal cortex and midbrain. It further reduced the expression of TH in the substantia nigra and striatum relative to vehicle-control (p

l-Arginine-nitric oxide pathway has been reported to be involved in the mediation of the psychopharmacological effects of many psychotropic drugs. Previous studies have shown that morin, a psychotropic compound isolated from mulberry leaf produces functional psychopharmacological effects indicative of antidepressant, antipsychotic, anxiolytic and nootropic properties. However, the role of l-arginine-nitric oxide pathway in the psychotropic effects of morin has not been fully investigated, hence, the need for this study. Male Swiss mice were pretreated individually or in combination with nitric oxide precursor [l-arginine (750 mg/kg, i.p.)], competitive nonselective nitric oxide synthase (NOS) inhibitor [N(G)-nitro-l-arginine methyl ester (l-NAME, i.p) (50 mg/kg)] or selective neuronal NOS inhibitor [methylene blue (3.75 mg/kg, i.p)] prior to morin (100 mg/kg, i.p.) or saline (10 mL/kg, i.p.) treatment. Psychopharmacological activities were then evaluated 30 min later using open field, Y-maze, and forced swim tests. l-Arginine significantly reversed the effects of morin on locomotion, memory and depression in mice. The reduced motor activity and enhanced memory function produced by morin were significantly attenuated by methylene blue but augmented the antimobility activity of morin in the FST. Moreover, l-NAME potentiated the psychopharmacological effects of morin in the open field and forced swim tests but reduced its memory promoting effect. Meanwhile, morin supplementation reversed the effects of l-arginine on l-NAME-treated mice in all behavioral models. The results of this study suggest that l-arginine-nitric oxide pathway might play a role in the modulation of the antidepressant and memory promoting effects of morin in mice.

Chrysophyllum albidum peel ethanol extract (CAPEE) was investigated for its antioxidant and hypolipidemic effects in rats. Dried peel was extracted in 70% ethanol and tested for phenolic content an...

Important underlying mechanisms of nitroglycerine tolerance development include oxidative stress and endothelial dysfunction, and there is paucity of information on how to reduce the tolerance during long-term administration. Taurine, a sulfonic amino acid, was reported to possess antioxidant, cardio-regulatory, neuro-modulatory, and membrane-stabilizing effect. The present study was designed to investigate the potential ability of taurine to prevent nitroglycerine-induced tolerance. The effect of taurine on nitroglycerin-induced tolerance was investigated in endothelium intact and endothelium-denuded aortic ring preparations. In the in vivo study, male Wistar rats were pre-treated with taurine for ten days and co-treated with nitroglycerin (GTN) 50 mg/kg for 3 days. Then, the aortic ring was harvested and tested in vitro for GTN tolerance. The serum was used to test for oxidative stress parameter (malondialdehyde, reduced glutathione (GSH), catalase (CAT)). Taurine (20 mM) co-incubated with GTN significantly augmented vasodilatory response to nitroglycerin (GTN) in endothelial-denuded aortic rings. Pre-treatment with taurine (100 and 200 mg/kg) also ameliorated GTN (50 mg/kg)-induced tolerance in isolated aortic ring in rats. Also, taurine (100 and 200 mg/kg) significantly (p

Objectives Cnidoscolus aconitifolius have been investigated to have abundant phytochemicals. However, study on the effect of Cnidoscolus aconitifolius on neurobehavioral performance when supplemented with diet is lacking. The study is aimed at investigating the memory-enhancing effect of Cnidoscolus aconitifolius-supplemented diet (CAD) using Morris water maze and Novel object recognition test. Methods Ninety male Wistar rats (80–100 g) were fed with CAD (1, 2.5, 5 and 10%) continuously for a period of 4, 8 and 12 weeks respectively. Six animals per group were used for assessment of memory performance (Morris water maze [MWM] and Novel object recognition test [NORT]); afterwards the brain tissues were harvested for malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) estimation. Acetylcholinesterase (AChE) concentration was also determined. Hippocampal architectural change in the neuron was examined using hematoxylin and eosin (H&E) and cresyl fast violet (Nissl) stain. Results Higher percentage of CAD significantly (pCornu Ammonis 3 (CA3) region. Conclusions The results suggest that CAD boost memory performance in rats through positive modulation of oxidative stress, cholinergic system and degeneration of hippocampal neurons.

Treatment-resistance depression and memory impairment disease, burdened with high levels of serious adverse effects of currently existing antidepressants and memory enhancers, have necessitated the search for alternative agents. Although previous preclinical studies have revealed the antidepressant-like and memory-enhancing potentials of morin, a compound isolated from Morus alba, the neurotransmitter receptor interaction mechanisms of action remain unknown. Hence, the role of monoaminergic and nonmonoaminergic neurotransmitter receptors in the antidepressant-like and memory-enhancing effects in naive mice were evaluated in this study. Male Swiss mice were pretreated intraperitoneally with D2-dopaminergic receptor antagonists (haloperidol), 5-HT1- and 5-HT2-receptor antagonist (metergoline), 5-HT synthesis inhibitor (para-chlorophenylalanine), α1-noradrenoceptor antagonist (prazosin), α2-noradrenoceptor antagonist (yohimbine), or cholinergic receptor antagonist (atropine) prior to the administration of morin (100 mg/kg, i.p.) or vehicle (10 mL/kg, i.p.). The memory-enhancing and antidepressant-like effects were then evaluated 30 min later using the open-field test (OFT), Y-maze test (YMT), and forced swim test (FST). Morin reduced locomotor activity however, it was reversed by metergoline, pCPA, prazosin, yohimbine, haloperidol, and atropine independent of their actions. Morin exhibited antidepressant property in the FST when compared with control (p < 0.05). Metergoline, para-chlorophenylalanine, prazosin, and haloperidol decreased the antidepressant-like activity of morin. Morin showed memory-enhancing effect in the YMT relative to control. Pretreatment with metergoline, para-chlorophenylalanine, or atropine, however, decreased the memory-promoting effect of morin. These findings suggest that the antidepressant-like activity exhibited by morin might be mediated via interactions with 5-HTergic, noradrenergic, and dopaminergic receptors, while the memory-enhancing effect might involve interaction with both 5-HTergic and cholinergic receptors.

Trastuzumab (TZM) is useful in the clinical management of HER2-positive metastatic breast, gastric, and colorectal carcinoma but has been limited by its off-target cardiotoxicity. This study investigates the therapeutic potentials of 0.25 mg/kg/day amlodipine, 0.035 mg/kg/day lisinopril, 5 mg/kg/day valsartan, and their fixed-dose combinations in TZM-intoxicated Wistar rats that were randomly allotted into 10 groups of 6 rats for each group. Group I rats were treated with 10 ml/kg/day sterile water orally and 1 ml/kg/day sterile water intraperitoneally; Groups II, III, and IV rats were orally gavaged with 5 mg/kg/day valsartan and 1 ml/kg/day sterile water intraperitoneally, 0.25 mg/kg/day amlodipine and 1 ml/kg/day sterile water via the intraperitoneal route, 0.035 mg/kg/day lisinopril and 1 ml/kg/day sterile water administered intraperitoneally, respectively. Group V rats were orally treated with 10 ml/kg/day of sterile water prior to intraperitoneal administration of 2.25 mg/kg/day of TZM. Groups VI–VIII rats were equally pretreated with 5 mg/kg/day valsartan, 0.25 mg/kg/day amlodipine, and 0.035 mg/kg/day lisinopril before intraperitoneal 2.25 mg/kg/day TZM treatment, respectively; Groups IX and X rats were orally pretreated with the fixed-dose combinations of 0.25 mg/kg/day amlodipine +0.035 mg/kg/day lisinopril and 5 mg/kg/day valsartan +0.035 mg/kg/day lisinopril, respectively, before TZM treatment. Cardiac injury and tissue oxidative stress markers, complete lipids profile, histopathological, and immunohistochemical assays were the evaluating endpoints. Results showed that repeated TZM treatments caused profound increases in the serum TG and VLDL-c levels, serum cTnI and LDH levels, and cardiac tissue caspase-3 and -9 levels but decreased BCL-2 expression. TZM also profoundly attenuated CAT, SOD, GST and GPx activities, and increased MDA levels in the treated tissues. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, the altered biochemical, histopathological, and immunohistochemical changes were reversed with amlodipine, lisinopril, valsartan, and fixed-dose combinations, although fixed-dose valsartan/lisinopril combination was further associated with hyperlipidemia and increased AI and CRI values and coronary artery cartilaginous metaplasia. Thus, the promising therapeutic potentials of amlodipine, lisinopril, valsartan and their fixed-dose combinations in the management of TZM cardiotoxicity, majorly mediated via antiapoptotic and oxidative stress inhibition mechanisms were unveiled through this study.

Cymbopogon citratus aqueous leaf extract (CYC) otherwise known as lemongrass tea is used for achy joints (rheumatism) and central nervous system disorders in ethnomedicine. This study was designed to investigate the effects of CYC on neurobehavioral, oxidative, and inflammatory changes produced by complete Freund adjuvant (CFA) in male Swiss mice. The mice were allotted into 6 groups (n = 6). The animals in group 1 received saline (control), group 2 also had saline (CFA-control), groups 3–5 received CYC (50, 100, or 200 mg/kg), whereas group 6 were given celecoxib (20 mg/kg) orally for 14 consecutive days. Mice in groups 2–6 also received 0.1 mL injection of CFA (10 mg/mL) into the left hind paw 30 min earlier on day 1. The paw volumes were measured on days 0, 7, and 14. Neurobehavioral changes were evaluated on day 14. Thereafter, the left hind paw tissues were processed for estimation of malondialdehyde, nitrite, glutathione, tumor necrosis factor-alpha, and interleukin-6 contents. The increase in paw volume and weight produced by CFA was reduced by CYC (p

Objectives Diosmin (DSM), commonly isolated from various plants, is a citrus nutrient that has been shown to increase intracellular antioxidant capacity and assuage symptoms associated with neurological disorders. Deficiency in the antioxidant system has been implicated in the pathogenesis of schizophrenia. The use of antioxidants as neuroprotectants to suppress schizophrenia pathology is increasingly being sought. Hence, this study investigated the effects of DSM on schizophrenia-like behavior and the underlying changes in biomarkers of oxidative stress and acetylcholinesterase (AChE) activity in mice. Methods The acute antipsychotic effect of DSM (25, 50, and 100 mg/kg, intraperitoneally [i.p.]), haloperidol (1 mg/kg, i.p.), and risperidone (RIS) (0.5 mg/kg, i.p.) was investigated on stereotyped behaviors induced by apomorphine (2 mg/kg, i.p.) and ketamine (10 mg/kg, i.p.). The effect of DSM on ketamine-induced hyperlocomotion, immobility enhancement, and its woodblock cataleptogenic potential was evaluated. Also, the subacute antipsychotic potential of DSM was assessed following intraperitoneal injection of DSM (25–100 mg/kg, i.p.) alone and in combination with ketamine (20 mg/kg, i.p.) for 10 days. The behaviors of the animals were assessed in the open-field, Y-maze, and forced swim tests. Brains of the animals were afterward processed for spectrophotometric assay of oxidative stress and AChE contents. Results DSM (25, 50, and 100 mg/kg) attenuated apormorphine-induced stereotypy and devoid of cataleptogenic effect. DSM and RIS reversed acute and subacute ketamine-induced schizophrenia-like behaviors. Disomin alone increased cognitive function and reduced despair-like phenotype. Furthermore, DSM increased superoxide dismutase and glutathione and decreased malondialdehyde and AChE levels in naïve and ketamine schizophrenic mice. Conclusions DSM prevents schizophrenia-like behavior, attenuates oxidative stress, and AChE activity in naïve and ketamine schizophrenic mice.

Apple cider vinegar (ACV), an acidic solution usually obtained from apple’s fermentation, is rich in polyphenols, compounds whose protective effects against neurodegenerative diseases is well documented. In view of this, the present study sought to evaluate the potential of ACV to attenuate lipopolysaccharide (LPS)-induced neurobehavioral deficits. Twenty-four Swiss mice randomly grouped into four (n = 6) were used for the study. Group 1 received normal saline, group 2 (LPS control) also received normal saline, while groups 3 and 4 respectively received ACV (10 mL/kg) for 7 days. LPS (0.5 mg/kg) was injected into animals in groups 2 and 4. Twenty-four hours (24 h) later, neurobehavioral deficits were evaluated in the animals using open field test (OFT), walk beam test (WBT), elevated plus maze (EPM), and forced swimming test (FST). Proinflammatory cytokines (TNF-α and IL-6) and nitrite, as well as malondialdehyde, reduced glutathione, and catalase activity, were assayed as biomarkers of brain inflammation and oxidative stress, respectively. The WBT, EPM, and FST analyses showed that pretreatment with ACV significantly (P

Purpose Fruit-based supplement has an important role in protecting the brain against oxido-inflammatory stress. Chrysophyllum albidum fruit contained several phytonutrients that possess antioxidants and anti-inflammatory properties. Hence, this study investigated the effect of C. albidum fruit supplemented diet (CAFD) on cognitive functions and lipopolysaccharide (LPS)-induced memory impairment and oxido-inflammatory response in mice. Methods Mice were randomized into two experiments. Experiment 1 with naïve mice contained four groups (n = 6) while experiment 2 with LPS contains five groups (n = 6). Mice in experiments 1 and 2 were fed on CAFD (5%, 10%, and 20%) in naïve (6 weeks) and LPS (250 μg/kg, i.p.) in the 7th week, respectively. Cognitive performance was tested using Y-maze test (YMT) and novel object recognition test (NORT) in the naïve and LPS mice. Brain samples were obtained for determination of oxido-inflammatory parameters and acetylcholinesterase activity. Results The CAFD significantly enhanced cognitive performance in the YMT and NORT in naïve and LPS mice, as evidenced by increased % alternation and discrimination index, respectively. CAFD supplementation significantly reduced acetylcholinesterase enzyme activity while it attenuated depletion of reduced glutathione and catalase activities in brains of naive and LPS-treated animals. The CAFD significantly reduced LPS-induced increased malondialdehyde levels in mice brains. CAFD supplementation significantly attenuated LPS-induced pro-inflammatory cytokines (IL-6, TNF-α) in mice brains. Conclusion Chrysophyllum albidum fruit supplementation in diet enhances memory function and prevents cognitive deficits induced by LPS via mechanisms associated with inhibition of oxidative stress-related processes, acetylcholinesterase activity, and pro-inflammatory mediators.

Objectives The juice extract of Cyperus esculentus commonly known as tiger nuts (TINUT) is widely used for its numerous health promoting effects including alleviation of symptoms associated with neurological disorders. Herein, we investigated the influence of the aqueous extract of C. esculentus on cognitive disorder and the underlying changes in acetylcholinesterase (AChE) activity and oxidative stress biomarkers in mice exposed to scopolamine. Methods C. esculentus (50–200 mg/kg) or saline (10 mL/kg) was given alone or with scopolamine 30 min after, to male Swiss mice (6/group) daily for seven days. We evaluated the cognitive performance using Y-maze and object recognition on day seven post-treatment. Brains of the animals were afterwards processed for spectrophotometric determination of AChE activity and contents of oxidative stress biomarkers (malondialdehyde [MDA], glutathione [GSH], catalase, superoxide dismutase and nitrite). Results The extract improves cognitive function and also upturned scopolamine amnesia in mice. The extract markedly reduced brain AChE, MDA, and nitrite contents in mice injected with scopolamine (p Conclusions The results of this study suggest that regular consumption of TINUT might offer beneficial effects in memory-related disorders.

The effects of Jobelyn® (JB) on neurological deficits and biochemical alterations associated with ischemic stroke induced by bilateral common carotid artery occlusion (BCCAO) in rats were investigated in this study. Male Wistar rats were divided into five groups (n = 8): group 1 served as Sham control; group 2, which served as negative control received normal saline while groups 3-5 were given JB (25, 50 and 100 mg/kg, p.o) daily for 28 days. Then, rats in groups 2-5 were subjected to BCCAO for 30 min and reperfusion afterwards. Neurological deficits were assessed 3 h post-reperfusion using a 9-point neurological scoring scale. The levels of biomarkers of oxidative stress and pro-inflammatory cytokines (tumour necrotic factor-α and interleukin-6), expressions of immunopositive cells of nuclear factor-kappa B (NF-κB) and acetyl-cholinesterase (AChE) activity were determined in brain tissues. Histology of the striatum, prefrontal cortex (PFC) and hippocampus (CA1) was also evaluated. JB improved BCCAO-induced neurological deficits and attenuated increased oxidative stress and AChE activity in rats subjected to BCCAO (p 0.05). Increased brain levels of tumour necrotic factor-α and interleukin-6 as well as expressions of immunopositive cells of NF-κB were decreased by JB. JB reduced brain damage and also increased population of viable neurons in the striatum, PFC and hippocampus of ischemic stroke rats. These findings suggest that the positive effect of JB on neurological function in rats with ischemic stroke may be related to inhibition of oxidative stress, release of pro-inflammatory cytokines and expressions of immunopositive cells of NF-κB.

Objectives The contribution of anesthetic procedure to surgical stress and postoperative complications has been attributed to increased oxidative stress and release of inflammatory cytokines. Thus, the levels of oxidative stress biomarkers and inflammatory cytokines in patients with general anesthesia (GA) and spinal anesthesia (SA) that underwent open reduction and internal fixation (ORIF) in orthopedic surgery at Federal Teaching Hospital, Ido-Ekiti, Ekiti state, Nigeria were investigated. Methods Forty patients were randomly distributed into two groups (n = 20) namely GA and SA. Blood samples were collected before and after surgery for estimation of glucose, oxidative stress biomarkers (malondialdehyde [MDA], glutathione, catalase and nitrile) and inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6) levels. Results The post-operative blood glucose level was higher than the pre-operative value (p Conclusions These findings suggest that anesthesia has differential effects on oxidative stress and inflammatory cytokines in patients with ORIF orthopedic surgery.

This study investigated the effect of methanolic leaf extract of Peristrophe Bicalyculata (MEPb) on type 2 diabetes mellitus (T2DM) associated cognitive decline in Wistar rats. 36 male rats weighing 130-200 g were assigned into 6 groups (n = 6) as follows: normal control, diabetic control, pioglitazone-treated diabetic and three MEPb-treated diabetic groups, type 2 diabetes mellitus was induced with low dose streptozocin (STZ) injection following 3 weeks of high fat diet (HFD) intake. Thirty days after diabetes induction, rats exhibited marked and persistent hyperglycemia, animals were treated with MEPb (50, 100 and 200 mg/kg) and pioglitazone (10 mg/kg) as standard. Morris water maze (MWM) test and Novel object recognition test (NORT) were used to assess learning and memory. Blood glucose level, oxidative stress makers, pro-inflammatory marker and acetylcholinestarase activities were analysed. Both MEPb and pioglitazone significantly (P < 0.05) reduced escape latency in treated animals compared to the diabetic control group in the MWM test. Methanolic leaf extract of Peristrophe bicalyculata and pioglitazone also significantly (P < 0.05) increased discrimination index in treated animals compared to the diabetic control group in the novel object recognition test. Serum, brain and liver MDA levels were significantly (P < 0.05) decreased in MEPb and pioglitazone treated rats compared to diabetic control. Serum and liver GSH as well as CAT levels were significantly (P < 0.05) increased while brain GSH and CAT levels shows apparent increase in MEPb and pioglitazone treated rats compared with diabetic control. Treatment with MEPb caused a significant (P < 0.05) decrease in brain nitrite level, interleukin 6 and acetylcholinesterase activity compared to diabetic control group. We conclude that Methanolic leaf extract of Peristrophe bicalyculata enhanced antioxidant capacity and prevented neuroinflammation, consequently improving brain neuronal cholinergic function in experimental animals.

Graphical abstract, Highlights • Acute oral dose of 2000 mg/kg of unripe B. sapida fruit extract (BSE) was toxic to mice. • Repeated treatment with BSE impaired locomotor function, memory performance and shortened seizure latency in mice. • Repeated treatment with BSE significantly up-regulate acetylcholinesterase enzyme activity in mice. • Repeated treatment with BSE elevates oxidative stress in the brain and liver of mice. • Repeated treatment with BSE showed histopathological evidences of toxicity in mice brain and liver., Ackee (Blighia sapida) is a commonly eaten fruit that is indigenous to West Africa and Jamaica. Ackee poisoning in young children have been reported in parts of Nigeria due to consumption of the unripe fruits. This study was designed to identify potential mechanisms of acute and sub-acute toxicity of unripe B. sapida fruit extract (BSE). Acute toxic effect was investigated in mice of either sex administered BSE 2000 mg/kg. The sub-acute toxicity effects were investigated in mice of either sex that received 28 days repeated administration of BSE (100 and 500 mg/kg, p.o.). Locomotor activity and memory performance were measured as well as seizure vulnerability in PTZ-induced model. Liver enzymes were assessed in the serum. Acetylcholinesterase, oxidative stress parameters and histopathological changes were assessed in the brain and liver tissues. Signs and symptoms of toxicity such as urination, tremor, depressed locomotion and death were observed in acute toxicity test. Sub-acute dosing caused significant impairment in locomotor activity and memory performance in mice. Seizure threshold was shortened in BSE-treated compared to control mice. Brain acetylcholinesterase activity was significantly increased. Alkaline phosphatase (ALP) was significantly elevated in mice that received BSE (500 mg/kg). Furthermore, BSE caused significant increase in oxidative stress expressed in nitrite, malondialdehyde, reduced glutathione and catalase in the brain and liver tissues. Histological staining revealed neuronal damage of brain hippocampus and hepatocellular swelling and necrosis. Blighia sapida unripe fruit extract increased susceptibility to seizure and impaired locomotor and memory function. The biochemical and histopathological findings revealed potential toxicity mechanisms related to neurotoxicity and hepatotoxicity.

Psychosocial stress has been widely reported to contribute to psychiatric disturbances. Perturbations in the enzymes of GABAergic and cholinergic systems have been implicated as precursors in different stress-related neuropsychiatric diseases. Targeting glutamic acid decarboxylase-67 kDa (GAD67) and acetylcholinesterase (AChE) via oxidative, nitrergic, and neuroinflammatory mechanisms have been recognized as prospective strategies for the prevention of psychosocial stress-induced behavioral impairments. Naringin, a neuro-active flavonoid compound isolated from citrus fruits, has been shown to produce memory-enhancing, antiepileptic, antidepressant, and anti-inflammatory activities similarly to ginseng, a very potent adaptogen. In this communication, we assessed the effect of naringin on social-defeat stress (SDS)-induced behavioral, GABAergic, cholinergic, oxidative, nitrergic, and neuroinflammatory changes in mice using the resident-intruder paradigm. The intruder male mice were culled into six groups. Groups 1 and 2 (normal- and SDS-controls) received sterile saline, groups 3-5 were given naringin (25-100 mg/kg, i.p.) whereas group 6 had ginseng (50 mg/kg, i.p.) daily for 14 days, but followed by 10 min SDS (physical and psychological) exposure to groups 2-6 with aggressor-resident mice. Behavioral effects using Y-maze, elevated-plus maze, sociability, and tail-suspension tests were assessed on day 14. GAD67, AChE enzymes, and biomarkers of oxidative, nitrergic, and neuroinflammatory changes were assayed in the striatum, prefrontal cortex, and hippocampus. Naringin and ginseng reversed all SDS-induced behavioral impairments. Naringin increased the levels of GAD67 and decreased AChE activities in the striatum, prefrontal cortex, and hippocampus. Furthermore, naringin reduced pro-inflammatory cytokines (TNF-α, IL-6), malondialdehyde, nitrite concentrations, and increased glutathione levels in a region-dependent manner. Our study suggests that naringin attenuated SDS-induced behavioral endophenotypes of neuropsychiatric disease through increased GAD67 synthesis, inhibition of AChE activity, oxidative, nitrergic stress, and neuroinflammatory processes in stress-sensitive brain regions.

Introduction Isoniazid-induced seizure, often described as Status Epilepticus (SE), is an emergency condition characterized by repeated convulsive episodes that responds poorly to the currently available anticonvulsant drugs. The current study aimed at ascertaining the effect of Jobelyn® (JB), an African dietary supplement, on seizures, altered oxidative stress, and glutamate decarboxylase activity induced by isoniazid in mice. Methods A total of 6 mice received JB (10-50 mg/kg, PO), pyridoxine (300 mg/kg), diazepam (5 mg/kg), or distilled water (10 mL/kg) 30 minutes prior to the induction of SE with injection of isoniazid (300 mg/kg, IP). Thereafter, the mice were observed for the onset of convulsions for a period of two hours. Moreover, the effect of JB on Glutamate Decarboxylase (GAD) activity and biomarkers of oxidative stress (glutathione and malondialdehyde) was also evaluated in the brain homogenates of another set of isoniazid-treated mice. Results JB (50 mg/kg, PO) prolonged the latency to convulsions, but could not prevent the occurrence of seizure episodes caused by isoniazid. Moreover, JB neither showed any protection against death nor delayed the latency to death caused by isoniazid. However, this dose of JB positively modulated the concentrations of malondialdehyde and glutathione in the brains of mice treated with isoniazid. The activity of GAD, the enzyme responsible for GABA synthesis, increased by JB, which suggested enhanced GABAergic neurotransmission. Conclusion The current study findings suggest that JB prolongs the latency to convulsions, enhances GABAergic neurotransmission, and demonstrates anti-oxidative effect in isoniazid-treated mice.

The aqueous leaf extract of Cymbopogon citratus (CYC) was evaluated for memory functions on scopolamine (SCO)-induced amnesia in mice. Male mice received CYC (25, 50, or 100 mg kg−1) or saline (10 ...

Evidence derived from preliminary studies suggests that morin, a neuroactive flavonoid with proven antioxidant and antiinflammatory properties possess antipsychotic-like activity. The present study was designed to evaluate the probable mechanisms involve in the antipsychotic-like activity of morin in ketamine model of schizophrenia. The effects of morin, haloperidol and risperidone on neurobehavioral and anti-schizophrenia-like effects were evaluated in mice (n = 7) following intraperitoneal (i.p.) administration of morin (25–100 mg/kg), haloperidol (1 mg/kg) and risperidone (0.5 mg/kg) alone or in combination with ketamine (20 mg/kg, i.p.) for 10 days. Neurobehavioral and schizophrenia-like activities consisting of open-field (positive symptoms), Y-maze, novel-object recognition (cognitive symptoms), social interaction (negative symptoms) tests were assessed. Also, wood-block catalepsy and rota-rod tests were employed to evaluate extrapyramidal side effects of morin. Thereafter, brain levels of biomarkers of oxidative, nitrergic and acetylcholinesterase alterations as well as histomorphological changes in the striatum and prefrontal-cortex were determined. Administration of morin and risperidone alone but not haloperidol significantly (p > 0.05) prevented ketamine-induced hyperlocomotion, social withdrawal and cognitive impairments relative to controls, and were devoid of extrapyramidal side effects. Morin alone or in combination with ketamine significantly increased glutathione concentration, superoxide dismutase and catalase activities compared with saline- or ketamine-treated mice. Moreover, morin alone or in combination with ketamine also significantly decreased malondialdehyde, nitrite and acetylcholinesterase alterations in mice brains. Furthermore, morin prevented ketamine-induced brain neuronal alterations in the striatum and prefrontal-cortex. Together, our findings suggest that morin may demonstrate antipsychotic-like therapeutic effect via modulation of oxidative/nitrergic, cholinergic actions and neuroprotection.

The effects of naringenin; a dietary flavonoid, with potent anti-oxidant and anti-inflammatory activities on social defeat stress (SDS)-induced neurobehavioral and biochemical changes were evaluated in mice using resident-intruder paradigm. The intruder male mice were distributed into 6 groups (n = 6). Mice in group 1 (control) received vehicle (3% DMSO, i.p), group 2 (SDS-control) were also given vehicle, groups 3-5 received naringenin (10, 25 and 50 mg/kg, i.p.) while group 6 had ginseng (50 mg/kg, i.p) daily for 14 days. However, 30 min after treatment on day 7, mice in groups 2-6 were exposed to SDS for a period of 10 min confrontation with aggressive counterparts for 7 consecutive days. Neurobehavioral phenotypes: spontaneous motor activity (SMA), memory, anxiety and depression were then evaluated on day 14. Malondialdehyde (MDA), glutathione (GSH), catalase and superoxide dismutase (SOD) were then estimated in the brain tissues. Acetylcholinesterase (AChE) activity and the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were also determined. SDS-induced neurobehavioral deficits were significantly (p 0.05) attenuated by naringenin. The increased brain level of MDA (13.00 ± 0.63 μmol/g tissue) relative to vehicle-control (6.50 ± 0.43 μmol/g tissue) was significantly (p 0.05) reduced to 5.50 ± 0.22 μmol/g tissue by naringenin (50 mg/kg). Mice exposed to SDS had decreased brain GSH level (5.17 ± 0.40 μmol/g tissue) relative to control (11.67 ± 0.84 μmol/g tissue). However, naringenin (50 mg/kg) significantly (p 0.05) elevated GSH content (13.33 ± 0.88 μmol/g tissue) in the brains of SDS-mice. Moreover, 50 mg/Kg of naringenin (38.13 ± 2.38 ρg/mL) attenuated (p 0.05) increased TNF-α level when compared with SDS (49.69 ± 2.81 ρg/mL). SDS-induced increase in brain level of IL-1β (236.5 ± 6.92 ρg/mL) was significantly (p 0.05) reduced by naringenin (219.90 ± 15.25 ρg/mL). Naringenin also elevated antioxidant enzymes and decreased AChE activity in the brains of mice exposed to SDS (p 0.05). These findings suggest that naringenin attenuates SDS-induced neurobehavioral deficits through inhibition of acetylcholinesterase activity, oxidative stress and release of pro-inflammatory cytokines.

Ethnopharmacological relevance The stem bark of Theobroma cacao L. have been used for the treatment of inflammation, toothache, measles and malaria in ethnomedicine. However, the anti-inflammatory activity of Theobroma cacao stem bark has not been fully elucidated. Aim The anti-inflammatory activity of Theobroma cacao stem bark ethanol extract and its fractions was investigated in this study. Materials and Methods The anti-inflammatory effect of ethanol extract of Theobroma cacao stem bark (EETc) and its dichloromethane (DCMF), ethylacetate (EAF) and aqueous (AQF) fractions was investigated in erythrocytes membrane stabilizing assay and carrageenan-induced paw oedema. The anti-inflammatory activity of the EAF and EETc was investigated in carrageenan induced-granuloma air pouch models. Results The extract and fractions showed significant membrane stabilizing action on rat erythrocytes cell membrane. The oral administration of DCMF, EAF and AQF (250 mg/kg) significantly inhibited paw oedema induced by carrageenan (41.3%, 55.0% and 45.0%, respectively) compared to control group. The EAF (62.5, 125 and 250 mg/kg) and EETc (250 mg/kg) significantly inhibited exudates formation in carrageenan air pouch by (63.8, 71.5, 74.5, 64.3%) at 24 h and by (69.4%, 75.7%, 77.1% and 68.4%) at 72 h respectively. The EETc and EAF significantly reduced neutrophil counts, protein, nitrite, Tumor necrosis factor (TNF-α) and malondialdehyde (MDA) but increased reduced glutathione (GSH) levels compared to control in pouch exudates. The HPLC fingerprint of EAF revealed presence of caffeic acid, rutin, ferulic acid and morin. Conclusion Ethanol extract of Theobroma cacao and its ethylacetate fraction demonstrated anti-inflammatory activity partly by reducing neutrophil migration and inflammatory mediator production.

The involvement of oxidative, nitrergic, cholinergic and inflammatory alterations have been reported to contribute to the pathophysiology of schizophrenia, a debilitating neuropsychiatric disorder. Our previous studies have shown that doxycycline (DOX), a notable member of tetracyclines with proven antioxidant and anti-inflammatory properties, attenuated psychotic-like behaviors induced by apomophine and ketamine (KET) in mice. This present study was designed to further evaluate in detail the ability of DOX and its combination with risperidone (RIS) to prevent and reverse KET-induced schizophrenic-like behaviors and the role of oxidative/nitrergic and cholinergic pathways in mice. In the prevention protocol, mice were treated orally with DOX (25, 50 or 100 mg/kg), RIS (0.5 mg/kg), DOX (50 mg/kg) in combination with RIS, or vehicle for 14 consecutive days. In addition, the animals received intraperitoneal injection of KET (20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the animals received KET or vehicle for 14 days prior to DOX, RIS, DOX in-combination with RIS or vehicle treatments. Schizophrenic-like behaviors consisting of positive, negative and cognitive symptoms were evaluated using open field, social interaction, Y-maze and novel object recognition tests. Thereafter, the brain levels of biomarkers of oxidative stress, nitrite and acetylcholinesterase activity were determined. DOX given alone or in combination with RIS attenuated schizophrenic-like behaviors induced by chronic injection of KET in both preventive and reversal treatment protocols. DOX significantly increased glutathione, superoxide dismutase and catalase levels in the brain of chronic KET-treated mice. However, it decreased malonyladehyde, nitrite levels and acetylcholinesterase activity when given alone or in-combination with RIS in both protocols. Taken together, these findings showed that doxycycline ameliorated schizophrenic-like behaviors induced by ketamine in both preventive and reversal treatment protocols in mice via inhibition of oxidative and nitrergic alterations, and acetylcholinesterase activity. Our data further suggests that adjunctive oral administration of doxycycline may augment the therapeutic efficacy of risperidone particularly for the treatment of negative and cognitive symptoms associated with schizophrenia.

GABAergic (Gamma-aminobutyric acid) and neurotrophic derangements have important implication in schizophrenia, a neuropsychiatric disease. Previous studies have shown that nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) alters GABAergic and neurotrophic activities via inflammatory and oxidative pathways. Thus, it has been proposed that agents with anti-oxidant and anti-inflammatory properties might be beneficial for the treatment of the disease. Morin is neuroactive bioflavonoid compound, which has been reported to demonstrate antipsychotic and anti-oxidant/anti-inflammatory activities. In this study, we further evaluated its effects on the brain markers of GABAergic, neurotrophic and oxidative alterations in the preventive and reversal of schizophrenia-like behavior induced by ketamine (KET). In the prevention protocol, adult mice were treated intraperitoneally with morin (100 mg/kg/day), haloperidol (1 mg/kg/day), risperidone (0.5 mg/kg/day), or saline (10 mL/kg/day) for 14 consecutive days. In addition, the animals were administered KET (20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the animals received KET or saline for 14 days. From 8th to 14th days mice were additionally treated with morin, haloperidol, risperidone or saline. Schizophrenic-like behaviors consisting of positive (stereotypy test), negative (behavioral despair in forced swim test) and cognitive (novel-object recognition test) symptoms were evaluated. Afterwards, brain levels of biomarkers of GABAergic (Glutamic acid decarboxylase-67, GAD67), neurotrophic (Brain-derived neurotrophic factor, BDNF) and oxidative [NADPH-oxidase, superoxide dismutase, (SOD) and catalase (CAT)] alterations were determined in the striatum, prefrontal cortex (PFC) and hippocampus, respectively. Morin significantly (p

Pineapple (Ananas comosus) peel is a major waste in pineapple canning industry and it is reported to be used in ethnomedicine as a component of herbal remedies for malarial management. This study aimed to evaluate the antimalarial, antinociceptive and anti-inflammatory properties of Ananas comosus peel extract (PEAC).Ananas comosus peel was extracted with 80% methanol. PEAC (100, 200 and 400 mg/kg) was investigated for antimalarial effect using Peter's 4-day suppressive test (4-DST) model in mice. Antinociceptive activity of PEAC was investigated in hot plate, acetic acid-induced writhing and formalin tests in mice. The anti-inflammatory activity was evaluated using the lipopolysaccharides-induced sickness behavior in mice and carrageenan-induced air pouch in rats' models.PEAC could not significantly (p 0.05) suppressed parasitemia level at 7-day post-infection in 4-DST. PEAC (400 mg/kg) mildly prolongs survival of infected mice up till day 21. PEAC demonstrated significant (p 0.05) antinociceptive activity by increasing latency to jump on the hot plate, reduced number of writhings in acetic acid test and reduced paw licking time in 2Ananas comosus peel extract demonstrated mild antimalarial activity but significant anti-nociceptive and anti-inflammatory properties probably mediated via inhibition of pro-inflammatory mediators.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the physical and psychosocial wellbeing of the patients and a major cause of work disability. Current drugs for its treatment only provide palliative effect, as cure for the disease still remains elusive. Jobelyn® (JB), a potent anti-oxidant and anti-inflammatory dietary supplement obtained from Sorghum bicolor, has been claimed to relieve arthritic pain. Thus, this study was designed to evaluate its effect on inflammatory and biochemical changes as well as neurobehavioural deficits associated with complete Freund-adjuvant (CFA)-induced arthritis in mice. The effect of JB (50, 100 and 200 mg/kg) on inflammatory oedema, neurobehavioural deficits, levels of biomarkers of oxidative stress and inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by 0.1 mL of CFA (10 mg/mL) was evaluated in male Swiss mice. Oral administration of JB (100 and 200 mg/kg) reduced inflammatory paw volume and reversed sensorimotor deficits induced by CFA. JB also reduced pain episodes, anxiety and depressive-like symptoms in CFA-mice. The increased level of oxidative stress in the joint and brain tissues of CFA-mice was reduced by JB. It also decreased tumor necrosis factor-alpha and interleukin-6 levels induced by CFA in the joint tissue of mice. These findings suggest that Jobelyn® attenuates inflammatory responses induced by CFA in mice via inhibition of oxidative stress and release of inflammatory cytokines. The ability of JB to attenuate CFA-induced nociception, sensorimotor deficits and depressive-like symptom suggests it might improve the quality of life of patients with arthritic conditions.

Preclinical Research The effects of methyl jasmonate (MJ; 5, 10, 20 mg/kg, i.p), a natural product widely used for the relief of stress, depression, and exhaustion on unpredictable chronic mild stress (UCMS)-induced depression-like behaviors in mice was assessed and compared to those of imipramine (IMP; 10 mg/kg, i.p). MJ and IMP were given 30 min before exposure to UCMS with the procedure repeated daily for 2 weeks; 24 h after the stress session, the tail suspension test (TST) and sucrose preference test were assessed. MJ decreased immobility time in the TST and reversed impaired intake of sucrose relative to the stressed control suggesting antidepressant-like activity. MJ also reduced UCMS-induced increases in corticosterone and MDA (malondialdehyde) levels and attenuated UCMS-induced decreases in GSH and TNF-α levels and SOD activity. These findings suggest that MJ attenuated UCMS-induced depressive-like behaviors through decreased levels of corticosterone and decreasing oxidative stress and neuroinflammation in mouse brain.Drug Dev Res 78 : 381-389, 2017. © 2017 Wiley Periodicals, Inc.

Anacardium occidentale stem bark has been reportedly used in the management of diabetes, inflammatory and oxidative stress conditions in folk medicine. In this study, the methanolic stem bark extract of Anacardium occidentale (MEAO) was evaluated for its hypolipidemic and antioxidant activities. Extract was obtained from powdered stem bark of A. occidentale by maceration in methanol (80%). Phytochemical screening, phenolic contents and free radical scavenging activity were determined in the extract. Animals were injected with Triton-X 100 (100 mg/kg, i.p.) to induce hyperlipidemia. MEAO (100, 200 and 400 mg/kg) and atorvastatin (10 mg/kg) were administered orally for 7 days. Serum, liver and heart tissue homogenates were used for determination of lipid profile and antioxidant assays. Alkaloids, flavonoids, saponins, tannins, anthraquinones, terpenoids and cardiac glycosides were found to be present in MEAO. Total phenolic content (TPC) and total flavonoid content (TFC) of MEAO were 129 mg GAE/g sample and 93.7 mg RE/g sample respectively. MEAO showed potent antioxidant activity with IC50 value of 42.44 ± 0.16 compared to ascorbic acid with 121.7 ± 0.04. Administration of MEAO resulted in a significant (p

Background: Vernonia amygdalina is well known as a medicinal plant in folk medicine as anti-diabetic, anthelmintic, antimalarial, laxative/purgative, and expectorant amongst others. Aim: This study was conducted to investigate the mechanisms of action of the anti-nociceptive and anti-inflammatory of Vernonia amygdalina. Materials and Methods: Methanol extract of Vernonia amygdalina leaf (MEVa) was evaluated for anti-nociceptive effect and possible mechanisms of action in the presence naloxone (1mg/kg), atropine (2mg/kg) and prazosin (1mg/kg) using acetic acid writhing test in mice. The anti-inflammatory effect was evaluated in carrageenan hind paw edema and carrageenan air pouch models. protein concentration, malondialdehyde, glutathione and superoxide dismutase assays were carried out for its anti-oxidative activities in inflammation. Hematoxylin and eosin staining were used to assess the level of inflammation. Results: From the acetic acid writhing test results, MEVa (50,100mg/kg) showed significant anti-nociceptive effect. Naloxone reversed the antinociceptive effect in comparison to atropine and prazosin. MEVa (50, 100 and 200 mg/kg) showed dose dependent inhibition of oedema (41.4, 63.0, 68.6%) at 4 h post carrageenan injection. In the carrageenan air pouch model, MEVa (200 mg/kg) reduced fluid exudation, infiltrating leucocytes and protein concentration. MEVa reduced MDA and prevented the depletion of GSH while increasing SOD activities. The histological study showed a reduction in the infiltration of inflammatory cells in MEVa-treated groups. Conclusion: Vernonia amygdalina might be carrying out its anti-nociceptive mechanism via the opioidergic system and its anti-inflammatory mechanism via reduction of leucocyte migration and lipid peroxidation. [J Complement Med Res 2017; 6(2.000): 192-198]

Preclinical Research Ocimum gratissimum L. leaves have attracted considerable attention from researchers because of their medicinal value that include anti-inflammatory, analgesic, antimicrobial, and antioxidant activities. In the present study, the toxicity and the protective effect of phenolic extract of O. gratissimum leaf (EAFOg) against acute inflammation and oxidative stress in rats was assessed. EAFOg, enriched in phenols had no cytotoxic effect against CHO-k1 cells, and no lethality against brine shrimp eggs or mice at a dose of 2000 mg/kg. EAFOg (50 and 100 mg/kg) reduced paw edema by 47% and 61%, compared to 29% with the COX-2 inhibitor, SC58125 (1 mg/kg) and 81% with indomethacin (5 mg/kg), respectively. In the rat carrageenan-induced air pouch model, EAFOg reduced exudate volume, leucocyte count, nitrite, TNF-α, and myeloperoxidase activity. EAFOg also protected against carrageenan-induced lipid peroxidation and glutathione depletion. These results provide evidence of the protective effects of EAFOg against acute inflammation and oxidative stress in rats. Drug Dev Res 78 : 135-145, 2017. © 2017 Wiley Periodicals, Inc.

Background Anxiety is a common ailment of high co-morbidity with epilepsy, a chronic neurologic disease characterized by recurrent seizures. Current drugs used for these conditions have several limitations such as disabling side effects, relapse, and ineffectiveness in certain population necessitating the search for alternative options. The aqueous leaf extract of Cymbopogon citratus (CYC) is widely used for its various health-promoting effects including relief of seizures and anxiety in ethnomedicine. This present study describes its effects on convulsions, anxiety-like behaviors, and social interaction in mice. Methods Male Swiss mice were pretreated orally with CYC (25, 50, and 100 mg/kg), diazepam (1 mg/kg), or distilled water (10 mL/kg) 60 min before induction of convulsions with intraperitoneal (i.p.) injection of picrotoxin (10 mg/kg), pentylenetetrazole (PTZ; 85 mg/kg), or isoniazid (300 mg/kg). The animals were then observed for the occurrence of seizure for 30 min or 2 h for isoniazid. The effects of CYC on anxiety-like behaviors, social interaction, and spontaneous motor activity (SMA) were evaluated in naive mice. Results CYC (25–100 mg/kg) did not prevent convulsions nor delay the latency to convulsions induced by picrotoxin, PTZ, or isoniazid. Pretreatment with CYC (50 and 100 mg/kg, p.o) produced anxiolytic-like effect, decreased SMA, and also enhanced social interaction behavior in naive mice. Conclusions The results of this study suggest that CYC did not exhibit an anticonvulsant property in mice injected with picrotoxin, PTZ, or isoniazid, but its anxiolytic-like activity and social interaction-promoting effect might be of benefit as an adjuvant in improving the quality of life of epileptic patients.

Morus mesozygia Stapf (Moraceae), commonly known as African mulberry, is traditionally used for the treatment of inflammatory disorders such as rheumatism and dermatitis.This work aimed to evaluate the anti-nociceptive and anti-inflammatory effects of its ethanol (EEMm) extract, and ethylacetate fraction (EAFMm).The anti-nociceptive and anti-inflammatory effect of ethanol extracts of M. mesozygia (EEMm), and its ethylacetate (EAFMm) and residual aqueous fraction (RAFMm) was evaluated in hotplate, acetic acid and formalin tests and as well in membrane stabilizing assay and carrageenan-induced paw oedema models. Mechanism of anti-inflammation of EAFMm was investigated in the carrageenan-induced air-pouch model.In the hot plate test of nociception, only the EAFMm showed significant (p 0.05) anti-nociceptive activity. The extract and fractions significantly reduced number of writhing with EAFMm (400 mg/kg) showing highest inhibition (66.5%) in the acetic acid-induced writhing in mice. EEMm and EAFMm (400 mg/kg) significantly reduced the paw licking time in the early and late phases of the formalin test. The extract and fractions showed good membrane stabilizing activity comparable to indomethacin. EAFMm (100 and 400 mg/kg) showed the highest inhibition of paw oedema (53.4% and 58.1%) in the carrageenan-induced paw oedema model. The EAFMm (100 and 400 mg/kg) reduced exudate volume relative to carrageenan-control (2.64 ± 0.22, 2.08 ± 0.15 vs 3.83 ± 0.18 mL) and neutrophils (8.98 ± 1.36, 8.00 ± 0.22 vs 20.51 ± 1.14) in carrageenan-induced pouch. EAFMm significantly reduced exudate volume, pro-inflammatory cytokines and the expression of COX-2 and NFκB.M. mesozygia leaves demonstrated anti-nociceptive and anti-inflammatory activities by suppressing oxidative stress, pro-inflammatory cytokines, cyclooxygenase-2, and nuclear factor kappa B.

d-Ribose-l-cysteine (DRLC), an analog of cysteine that boosts glutathione (GSH) content, has been reported to mitigate oxidative stress–mediated diseases. This study seeks to evaluate the effects of DRLC on memory deficits and the biochemical and histo-morphological changes induced by lipopolysaccharide (LPS) in mice. Male Swiss mice (n = 10) were pre-treated orally with three doses of DRLC (25 mg/kg, 50 mg/kg, and 100 mg/kg), donepezil (1 mg/kg), or vehicle (saline) for 30 min prior to the intraperitoneal injection of LPS (0.25 mg/kg) daily for 7 days. Memory functions were evaluated using the Y-maze, object recognition, and social recognition tests. The specific brain regions (prefrontal cortex and hippocampus) were evaluated to determine oxidative stress biomarkers (malondialdehyde, GSH, and catalase), acetyl-cholinesterase activity, proinflammatory cytokines (tumor necrosis factor-α and interleukin-6), expression of nuclear factor-kappa B (NF-κB), and neuronal cell morphology. DRLC (25–100 mg/kg) reversed the memory deficits in the LPS-treated mice (p

Aim: Chenopodium opulifolium is a specie of the Chenopodiaceae commonly used as vegetables in local diet and for treating different ailment in Uganda. This study was conducted to evaluate the antioxidant, antinociceptive and anti-inflammatory effects of the aqueous extract of C opulifolium leaves (AECo). Methods: The dried leaf of the plant was extracted by maceration in water. Qualitative and quantitative phytochemical analysis, antioxidants and membrane stabilizing effects were determined in the extract. The extract was then investigated for acute toxicity effect, antinociceptive (writhing, hot plate and open field test) and anti-inflammatory (egg albumin-induced paw oedema) in rodents. Results: Phytochemical analysis revealed the presence of alkaloids, tannins, phlobatannins, flavonoids and saponins in AECo. Total caffeic acid derivatives and total flavonoids content yields 91.7 mgCAE/g sample and 94.7 mgRE/g sample, respectively. AECo demonstrated antioxidant effects in both DPPH and NO assays. Significant membrane stabilizing activity was observed in both the heat and hypotonic solution-induced lysis of erythrocytes. The acute toxicity test showed that AECo (5000 mg/kg) did not cause any significant change in behavior or death in rats. AECo (100-400 mg/kg) produced a significant antinociceptive effects in both the writhing and hot plate tests, but no significant reduction in the locomotory activity in mice. Furthermore, the extract significantly (p < 0.05) reduced egg albumin-induced rat paw oedema by 44.2, 44.5, and 51.2 %, respectively after 120 min. Conclusion: The results denote that Chenopodium opulifolium extract has significant antioxidant, antinociceptive and anti-inflammatory effects, and these affirm the reasons for its folkloric use.