Neuroprotective effects of Aframomum pruinosum seed extract against stroke in rat: Role of antioxidant and anti-inflammatory mechanisms.

BACKGROUND: Stroke is a major cause of disability and neurological impairment worldwide. Effective prevention and management strategies are needed to reduce its burden. This study aimed to investigate the therapeutic effect of the seed ethanolic extract of Aframomum pruinosum (EEAP) on stroke and its related motor and cognitive deficits in rats. MATERIALS AND METHODS: Stroke was induced by either middle cerebral artery occlusion (MCAO) or bilateral common carotid artery occlusion (BCCAO). In the MCAO model, rats received EEAP (75, 150, or 300 mg kg-1) or N-acetyl-L-cysteine (100 mg kg-1) orally for one week before 2 h of occlusion, followed by reperfusion. Twenty-four hours after ischemia, brain was collected for infarct size using 2, 3, 5 -TriphenylTetrazolium Chloride (TTC) staining, oxidative stress markers and inflammatory cytokines (TNF-α, IL-1ß) measurements. In the BCCAO model, rats underwent occlusion for 30 min and received EEAP or quercetin (25 mg kg-1) for 7 days post-induction. Behavioral parameters were evaluated at the end of the treatment. Oxidative stress and inflammatory markers were measured in the cerebrum and cerebellum. RESULTS: MCAO caused significant brain infarction, and increased lipid peroxidation, TNF-α and IL-1ß contents. EEAP, rich in nerolidol, prevented these changes in a dose-dependent manner. BCCAO impaired the neurological function, mobility, and muscle strength of rats. It also increased lipid peroxidation and inflammatory cytokines in the cerebellum. EEAP significantly ameliorated these impairments. CONCLUSION: EEAP exerts preventive and curative neuroprotective effects against ischemic stroke and its associated motor impairments at least partially through its antioxidant and anti-inflammatory properties, and its nerolidol content.

The antioxidant and neuroprotective effects of the Psychotria camptopus Verd. Hook. (Rubiaceae) stem bark methanol extract contributes to its antiepileptogenic activity against pentylenetetrazol kindling in male Wistar rats.

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.

Alcohol-exacerbates post-traumatic stress psychiatric behavior and its neuropathological sequalae in experimental mice: preventive effects of morin.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2g/kg, oral gavage) every other day, alongside daily morin (50 and 100mg/kg) or fluoxetine (10mg/kg) from days 8-21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal-cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin prevented TNF-α, and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.

Antipsychotic effect of diosgenin in ketamine-induced murine model of schizophrenia: Involvement of oxidative stress and cholinergic transmission.

A decrease in the levels of antioxidant arsenals exacerbate generation of reactive oxygen/nitrogen species, leading to neurochemical dysfunction, with significant impact on the pathogenesis of psychotic disorders such as schizophrenia. This study examined the preventive and reversal effects of diosgenin, a phyto-steroidal saponin with antioxidant functions in mice treated with ketamine which closely replicates schizophrenia-like symptoms in human and laboratory animals. In the preventive phase, adult mice cohorts were clustered into 5 groups (n = 9). Groups 1 and 2 received saline (10 mL/kg, i.p.), groups 3 and 4 were pretreated with diosgenin (25 and 50 mg/kg), and group 5 received risperidone (0.5 mg/kg) orally for 14 days. Mice in groups 2-5 additionally received a daily dose of ketamine (20 mg/kg, i.p.) or saline (10 mL/kg/day, i.p.). In the reversal phase, mice received intraperitoneal injection of ketamine or saline for 14 consecutive days prior to diosgenin (25 and 50 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) treatment from days 8-14. Mice were assessed for behavioral changes. Oxidative, nitrergic markers, and cholinergic (acetylcholinesterase activity) transmission were examined in the striatum, prefrontal-cortex and hippocampus. Diosgenin prevented and reversed hyperlocomotion, cognitive and social deficits in mice treated with ketamine relative to ketamine groups. The increased acetylcholinesterase, malondialdehyde and nitrite levels produced by ketamine were reduced by diosgenin in the striatum, prefrontal-cortex and hippocampus, but did not reverse striatal nitrite level. Diosgenin increased glutathione, and catalase levels, except for hippocampal catalase activity when compared with ketamine controls. Conclusively, these biochemical changes might be related to the behavioral deficits in ketamine-treated mice, which were prevented and reversed by diosgenin.

Depression in Sub-Saharan Africa.

Mood disorders can be considered among the most common and debilitating mental disorders. Major depression, as an example of mood disorders, is known to severely reduce the quality of life as well as psychosocial functioning of those affected. Its impact on the burden of disease worldwide has been enormous, with the World Health Organisation projecting depression to be the leading cause of mental illness by 2030. Despite several studies on the subject, little has been done to contextualise the condition in Africa, coupled with the fact that there is still much to be understood on the subject. This review attempts to shed more light on the prevalence of depression in Sub-Saharan Africa (SSA), its pathophysiology, risk factors, diagnosis and the experimental models available to study depression within the sub-region. It also evaluates the contribution of the sub-region to the global research output of depression as well as bottlenecks associated with full exploitation of the sub region's resources to manage the disorder.

Anticonvulsant effects of the aqueous and methanol extracts from the stem bark of Psychotria camptopus Verdc. (Rubiacaea) in rats.

ETHNOPHARMACOLOGY RELEVANCE: The decoction from the stem bark of Psychotria camptopus (Rubiaceae) is used in the Cameroonian pharmacopoeia to treat neurological pathologies including epilepsy. AIM: The present work was undertaken to study the anticonvulsant properties of the aqueous (AE) and methanol (ME) extracts from the stem bark of P. camptopus in acute models of epileptic seizures in Wistar rats. METHOD: AE and ME were obtained by decoction and maceration of the stem bark powder in water and methanol, respectively. They were tested orally at the doses of 40, 80 and 120 mg/kg, on the latency of onset and duration of epileptic seizures induced by pentylene tetrazole (PTZ, 70 mg/kg, i.p.). The kinetic effect of both extracts at 120 mg/kg was evaluated. Their effects on diazepam (50 mg/kg) induced sleep and strychnine (STR, 2.5 mg/kg, i.p.) induced seizures were determined. ME was further tested on picrotoxin (PIC, 7.5 mg/kg, i.p.) and thiosemicarbazide (TSC, 50 mg/kg, i.p.) induced seizure models. The phytochemical composition of ME was assessed using LC-MS method, as well as its acute toxicity. RESULTS: AE and ME significantly (p < 0.001) reduced the duration of seizures in both PTZ and STR models. Their maximal effect was observed at 1 h after administration, though their effect at 120 mg/kg was maintained (p < 0.05) up to 24 h post-treatment. Both extracts significantly (p < 0.01) reduced sleep duration. ME significantly (p < 0.001) increased the latency of rat death on PIC-induced convulsions. In TSC rats, ME significantly (p < 0.001) delayed the latency to the first convulsion, and decreased the duration and frequency of convulsions. ME showed no acute toxicity while its phytochemical screening revealed the presence of two flavonoids (Rutin and Butin), two triterpenoid saponins (Psycotrianoside B and Bauerenone) and four alkaloids (10-Hydroxy-antirhine, 10-hydroxy-iso-deppeaninol, Emetine and Hodkinsine). In conclusion, AE and ME from the stem bark of P. camptopus have comparable anticonvulsant properties. The effect of ME is likely due to the presence of flavonoids and alkaloid and the activation of GABA pathway. These results further justify and support the use of P. camptopus in traditional medicine for the treatment of epilepsy.