Diosgenin alleviates alcohol-mediated escalation of social defeat stress and the neurobiological sequalae.

RATIONALE: Emerging evidence indicates that persistent alcohol consumption escalates psychosocial trauma achieved by social defeat stress (SDS)-induced neurobiological changes and behavioral outcomes. Treatment with compounds with neuroprotective functions is believed to reverse ethanol (EtOH)-aggravated SDS-induced behavioral impairments. OBJECTIVES: We investigated the outcomes of diosgenin treatment, a phytosteroidal sapogenin in mice co-exposed to repeated SDS and EtOH administration. METHODS: During a period of 14 days, SDS male mice were repeatedly administered EtOH (20%, 10 mL/kg) orally from days 8-14 (n = 9). Within days 1-14, SDS mice fed with EtOH were simultaneously treated with diosgenin (25 and 50 mg/kg) or fluoxetine (10 mg/kg) by oral gavage. Locomotor, cognitive-, depressive-, and anxiety-like behaviors were assessed. Adrenal weight, serum glucose, and corticosterone levels were assayed. Brain markers of oxido-inflammatory, neurochemical levels, monoamine oxidase-B, and acetylcholinesterase activities were measured in the striatum, prefrontal cortex, and hippocampus. RESULTS: The anxiety-like behavior, depression, low stress resilience, social, and spatial/non-spatial memory decline exhibited by SDS mice exposed to repeated EtOH administration were alleviated by diosgenin (25 and 50 mg/kg) and fluoxetine, illustrated by increased dopamine and serotonin concentrations and reduced monoamine oxidase-B and acetylcholinesterase activities in the prefrontal cortex, hippocampus, and striatum. Diosgenin attenuated SDS + EtOH interaction induced corticosterone release and adrenal hypertrophy, accompanied by reduced TNF-α, IL-6, malondialdehyde, and nitrite levels in the striatum, prefrontal cortex, and hippocampus. Diosgenin increased glutathione, superoxide dismutase, and catalase levels in SDS + EtOH-exposed mice. CONCLUSIONS: Our data suggest that diosgenin reverses SDS + EtOH interaction-induced behavioral changes via normalization of hypothalamic-pituitary-adrenal axis, neurochemical neurotransmissions, and inhibition of oxidative and inflammatory mediators in mice brains.

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.

Geraniol attenuates behavioral and neurochemical impairments by inhibitions of HPA-axis and oxido-inflammatory perturbations in mice exposed to post-traumatic stress disorder.

Geraniol is an acyclic isoprenoid monoterpenoid analogue that has been shown to elicit neuroprotective functions, primarily through its ability to stimulate antioxidant and anti-inflammatory systems. An increase in inflammatory cytokines and oxidative stress exacerbate activation hypothalamic-pituitary-adrenal axis (HPA), leading to neurochemical dysfunction, which has important roles in the pathogenesis of post-traumatic disorder (PTSD), a mental health disorder characterized of post-trauma-induced intense fear. The aim of this study was to evaluate the anti-PTSD-like effects and underlying mechanisms of geraniol against single-prolonged-stress (SPS)-induced PTSD in mice. Following concomitant exposure to SPS (triple-paradigm traumatic events) and isolation for 7 days, mice (n = 9) were treated with geraniol (50 and 100 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.) from days 8-21. Mice were assessed for behavioral changes. Neurochemical changes, inflammatory, oxido-nitrergic markers, adrenal weight, serum glucose and corticosterone concentrations were assayed. Geraniol inhibits SPS-induced anxiety- and depressive-like features as well as behavioral despair in the depression paradigms. SPS-induced locomotor and memory impairments were also abated by geraniol treatment similarly to fluoxetine. SPS-induced adrenal hypertrophy and increased blood glucose and corticosterone concentrations, were attenuated by the geraniol treatment. Elevated levels of TNF-α and IL-6, and malondialdehyde, nitrite, acetylcholinesterase enzyme were reduced by geraniol. Geraniol also increased glutathione, superoxide-dismutase, and catalase levels as well as dopamine, serotonin concentrations and GABAergic glutamic acid decarboxylase enzyme activity in the striatum, prefrontal cortex and hippocampus in the PTSD-mice relative to SPS control. In conclusion, geraniol attenuates behavioral impairments and neurochemical dysregulations by inhibitions of HPA-axis and oxido-inflammatory perturbations in mice exposed to PTSD.

Mechanisms underpinning Carpolobia lutea G. Don ethanol extract's neurorestorative and antipsychotic-like activities in an NMDA receptor antagonist model of schizophrenia.

ETHNOPHARMACOLOGICAL RELEVANCE: Persistent ketamine insults to the central nervous system block NMDA receptors and disrupt putative neurotransmission, oxido-nitrosative, and inflammatory pathways, resulting in schizophrenia-like symptoms in animals. Previously, the ethnomedicinal benefits of Carpolobia lutea against insomnia, migraine headache, and insanity has been documented, but the mechanisms of action remain incomplete. AIM OF THE STUDY: Presently, we explored the neuro-therapeutic role of Carpolobia lutea ethanol extract (C. lutea) in ketamine-induced schizophrenia-like symptoms in mice. MATERIALS AND METHODS: Sixty-four male Swiss (22 ± 2 g) mice were randomly assigned into eight groups (n = 8/group) and exposed to a reversal ketamine model of schizophrenia. For 14 days, either distilled water (10 mL/kg; p.o.) or ketamine (20 mg/kg; i.p.) was administered, following possible reversal treatments with C. lutea (100, 200, 400, and 800 mg/kg; p.o.), haloperidol (1 mg/kg, p.o.), or clozapine (5 mg/kg; p.o.) beginning on days 8-14. During the experiment, a battery of behavioral characterizations defining schizophrenia-like symptoms were obtained using ANY-maze software, followed by neurochemical, oxido-inflammatory and histological assessments in the mice brains. RESULTS: A 7-day reversal treatment with C. lutea reversed predictors of positive, negative and cognitive symptoms of schizophrenia. C. lutea also mitigated ketamine-induced neurochemical derangements as evidenced by modulations of dopamine, glutamate, norepinephrine and serotonin neurotransmission. Also, the increased acetylcholinesterase activity, malondialdehyde nitrite, interleukin-6 and tumor necrosis-factor-α concentrations were reversed by C. lutea accompanied with elevated levels of catalase, superoxide dismutase and reduced glutathione. Furthermore, C. lutea reversed ketamine-induced neuronal alterations in the prefrontal cortex, hippocampus and cerebellum sections of the brain. CONCLUSION: These findings suggest that C. lutea reverses the cardinal symptoms of ketamine-induced schizophrenia in a dose-dependent fashion by modulating the oxido-inflammatory and neurotransmitter-related mechanisms.

Psychobiotic interventions attenuate chronic alcohol use-mediated exacerbation of posttraumatic stress disorder in rats: the role of gut-liver axis response.

OBJECTIVES: The incidence of co-occurring alcohol-use disorder (AUD) and post-traumatic stress disorder (PTSD) is high, and the presence of one disorder aggravates the severity of the other. Emerging evidence shows the neuroprotective and anti-inflammation functions of psychobiotics. Hence, the study explored the effects of probiotics and synbiotic inulin on the gut- and liver-oxidative and inflammatory biomarkers in chronic alcohol exacerbation of PTSD symptoms in rats. METHODS: Young adult rats were administered 10% ethanol in a two-bottle choice test for six weeks and were subjected to single prolonged stress. Probiotics and synbiotic intervention followed this. Markers of oxido-inflammatory stress, liver functions, intestinal (faecal) metabolites, occludin expression, and histopathology of the ileum and liver were evaluated. RESULTS: Chronic alcohol drinking and PTSD increased oxido-inflammatory stress, markers of hepatic damage, and reduced faecal metabolites, which were attenuated by probiotic and synbiotic interventions. Furthermore, reduced immunoexpression of gut and liver occludin, with loss of barrier integrity, viable hepatocytes, congestive portal area, and shortened villi and crypt depth, were observed. Probiotic and synbiotic interventions mitigated these effects. CONCLUSIONS: The study demonstrates that psychobiotics mitigate the detrimental effects of co-occurring chronic alcohol intake in the context of PTSD.

Normalization of HPA Axis, Cholinergic Neurotransmission, and Inhibiting Brain Oxidative and Inflammatory Dynamics Are Associated with The Adaptogenic-like Effect of Rutin Against Psychosocial Defeat Stress.

Social defeat stress (SDS) due to changes in biochemical functions has been implicated in the pathogenesis of affective and cognitive disorders. Employing pharmacological approach with adaptogens in the management and treatment of psychosocial stress is increasingly receiving scientific attention. In this study, we investigated the neuroprotective effect of rutin, a bioflavonoid with neuroprotective and anti-inflammatory functions on neurobehavioral and neuro-biochemical changes in mice exposed to SDS. Groups of mice named the intruder mice received normal saline (10 mL/kg), rutin (5, 10, and 20 mg/kg, i.p.), and ginseng (50 mg/kg, i.p.) daily for 14 days, and then followed by 10 min daily SDS (physical/psychological) exposures to aggressor mice from days 7-14. Investigations consisting of neurobehavioral (locomotion, memory, anxiety, and depression) phenotypes, neuro-biochemical (oxidative, nitrergic, cholinergic, and pro-inflammatory cytokines) levels in discrete brain regions, and hypothalamic-pituitary-adrenal (HPA) axis consisting adrenal weight, corticosterone, and glucose concentrations were assessed. Rutin restored the neurobehavioral deficits and reduced the activity of acetylcholinesterase in the brains. Adrenal hypertrophy, increased serum glucose and corticosterone levels were significantly attenuated by rutin. SDS-induced release of tumor necrosis factor-alpha and interleukin-6 in the striatum, prefrontal cortex, and hippocampus were also suppressed by rutin in a brain-region-dependent manner. Moreover, SDS-induced oxidative stress characterized by low antioxidants (glutathione, superoxide-dismutase, catalase) and lipid peroxidation and nitrergic stress were reversed by rutin in discrete brain regions. Collectively, our data suggest that rutin possesses an adoptogenic potential in mice exposed to SDS via normalization of HPA, oxidative/nitrergic, and neuroinflammatory inhibitions. Thus, may be adopted in the management of neuropsychiatric syndrome due to psychosocial stress.

Possible mechanisms involved in the testicular-protective property of quercetin in rats exposed to endosulfan toxicity.

The study investigated the effects of quercetin and putative mechanisms involved against endosulfan-testicular impairments in rats. Rats were allotted into five treatment groups (n = 5). Groups 1-2 had normal saline and maize oil (vehicle) (10 mL/kg), group 3 received quercetin (20 mg/kg), 4-5 had endosulfan (5 mg/kg, p.o) orally for 28 days. However, from days 14-28, group 4 received an additional dose of vehicle (10 mL/kg, p.o./day), while group 5 received quercetin (20 mg/kg, p.o./day). Thereafter, blood samples and testes were harvested for markers of cholinergic, hormonal and testicular oxido-nitrergic, inflammatory, apoptosis and proton pump ATPase activities. Also, testicular histopathological changes were also evaluated alongside with germ cell count, testicular injury and spermatogenesis score. Quercetin increased testicular/body weights and spermatogenesis, androgenic hormones (follicle stimulating hormones, FSH; luteinizing hormone, LH; testosterone), acetylcholinesterase levels and attenuated altered membrane integrity, DNA fragmentation, increased caspases-3 levels in rats exposed to endosulfan. Moreover, quercetin increased testicular B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x-protein (Bax) and proton pump adenosine trisphosphate (ATPase) and sialic acid levels. Of note, quercetin reversed endosulfan-mediated increased malondialdehyde, nitrite, peroxynitrite formation, 8-hydroxy-2'-deoxyguanosine and lowered antioxidant enzymes in the testes. The increased levels of testicular myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) by endosulfan were also reduced by quercetin administration. Additionally, quercetin attenuate endosulfan-induced testicular histopathological changes of rats. Our findings showed that quercetin significantly inhibited endosulfan-induced testicular damage and altered spermatogenesis through inhibition of oxido-nitrergic pathway, inflammatory mediators, apoptosis, acetylcholinesterase activity and enhancement of testicular hormones and improvement in testicular ATPase activity.

Treatment with Ginkgo biloba supplement modulates oxidative disturbances, inflammation and vascular functions in oxygen deprived hypothyroid mice: Involvement of endothelin-1/NO signaling pathways.

A double-hit biological alteration involving exposure to oxygen deprivation in hypothyroid condition may exacerbate cellular oxidative and inflammatory disturbances comparative to a one-hit biological exposure. This study investigated the therapeutic effect of Ginkgo biloba as cardioprotective against aortic oxido-inflammatory disturbances following oxygen deprivation in hypothyroid mice. Male Swiss mice were partitioned into 5 groups (n = 6) for hypothyroidism (Carbimazole 1.2 mg/kg) and hypoxia induction. Group 1 (normal control), group 2 (hypoxic stress control), group 3 (hypoxic and hypothyroid stress), group 4 (hypoxic and hypothyroid stress and Ginkgo biloba 20 mg/kg; p.o) and group 5 (hypoxic and hypothyroid stress and Levothyroxine 10 µg/kg; p.o) for 14 days. Thereafter, serum and aorta was collected for biochemical evaluation. GBS did not up-regulate the serum thyroid hormone imbalances (tri-iodothyronine (T3), thyroxin (T4)) but maintains the TSH levels. The blood glucose level was reduced with decrease oxidative stress and inflammatory mediators in the serum/aorta indicated by inhibited redox status following treatment with GBS. Moreover, endothelin-1/nitric oxide signaling pathways were markedly regulated in the aorta. Conclusively, GBS acts as a therapeutic agent and may be consider as a potential vasodilator candidate in the management and control of hypoxic stress in hypothyroid condition. PRACTICAL APPLICATIONS: Treatment with Gingko biloba supplement abated endothelial abnormalities via elevation of nitric oxide release and suppression of endothelin activity in hypothyroid mice exposed to hypoxic hypoxia. The activity of myeloperoxidase enzyme and redo-inflammatory status was downregulated following treatment with Gingko biloba supplement in hypothyroid mice exposed to hypoxic hypoxia. Treatment with Gingko biloba supplement modulates hypothalamic-pituitary-adrenal (HPA) axis by inhibiting corticosterone release in hypothyroid mice exposed to hypoxic hypoxia.

Taurine, an essential ß-amino acid insulates against ketamine-induced experimental psychosis by enhancement of cholinergic neurotransmission, inhibition of oxidative/nitrergic imbalances, and suppression of COX-2/iNOS immunoreactions in mice.

Cholinergic, oxidative, nitrergic alterations, and neuroinflammation are some key neuropathological features common in schizophrenia disease. They involve complex biological processes that alter normal behavior. The present treatments used in the management of the disorder remain ineffective together with some serious side effects as one of their setbacks. Taurine is a naturally occurring essential ß-amino acid reported to elicit antipsychotic property in first episode psychosis in clinical setting, thus require preclinical investigation. Hence, we set out to investigate the effects of taurine in the prevention and reversal of ketamine-induced psychotic-like behaviors and the associated putative neurobiological mechanisms underlying its effects. Adult male Swiss mice were sheared into three separate cohorts of experiments (n = 7): drug alone, preventive and reversal studies. Treatments consisted of saline (10 mL/kg/p.o./day), taurine (50 and 100 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) with concomitant ketamine (20 mg/kg/i.p./day) injections between days 8-14, or 14 days entirely. Behavioral hyperactivity, despair, cognitive impairment, and catalepsy were measured. Brain oxidative/nitrergic imbalance, immunoreactivity (COX-2 and iNOS), and cholinergic markers were determined in the striatum, prefrontal-cortex, and hippocampus. Taurine abates ketamine-mediated psychotic-like episodes without cataleptogenic potential. Taurine attenuated ketamine-induced decrease in glutathione, superoxide-dismutase and catalase levels in the striatum, prefrontal-cortex and hippocampus. Also, taurine prevented and reversed ketamine-mediated elevation of malondialdehyde, nitrite contents, acetylcholinesterase activity, and suppressed COX-2 and iNOS expressions in a brain-region dependent manner. Conclusively, taurine insulates against ketamine-mediated psychotic phenotype by normalizing brain central cholinergic neurotransmissions, oxidative, nitrergic and suppression of immunoreactive proteins in mice brains.

The Anti-Parkinson Potential of Gingko biloba-Supplement Mitigates Cortico-Cerebellar Degeneration and Neuropathobiological Alterations via Inflammatory and Apoptotic Mediators in Mice.

Activation of nuclear factor erythroid 2 related factor 2 (Nrf2) associated with the suppression of various oxido-inflammatory pathways and the controller of several gene expressions involving "antioxidant response elements" (AREs) in their promoters to mediate and restores homeostatic functions is now considered as one of the main switch regulating the immune response, and it is also now involved in inflammatory cascade in PD. Whether therapeutic approach using Ginkgo biloba would have significant protective effects against cortico-cerebellar dopaminergic degeneration in rotenone-induced mice remains unknown. In this present study, we studied the therapeutic effects of Ginkgo biloba-supplement (Gb-S) administration in cortico-cerebellar dopaminergic degeneration. The results revealed that treatment with Gb-S suppresses cognitive decline and neuromuscular incompetence in the mice, abated tyrosine hydroxylase depletion and synucleinopathy development in the cortico-cerebellar neurons of the mice before and after rotenone induction. However, our data further shows increase Nrf2 immunoexpression with decrease oxido-nitrergic and neuroinflammatory release, increase cholinergic enzyme activity and downregulated executioner caspase-3 that may mediate cortico-cerebellar apoptosis. Also, the loss of cortico-cerebellar neurons was attenuated, marked by increase in dendritic spine length and width with numerous viable neurons. Overall findings suggest that Gb-S could be a potential pharmacotherapeutic candidate providing a strong protection for cortico-cerebellar neurocellular substances and against Parkinsonism-like non-motor and motor symptoms.

Ginkgo biloba protects striatal neurodegeneration and gut phagoinflammatory damage in rotenone-induced mice model of Parkinson's disease: Role of executioner caspase-3/Nrf2/ARE signaling.

Asymptomatic and early clinical stages of Parkinson's disease (PD) have been linked with comorbid non-motor symptoms including dysfunction of the gastrointestinal (GI) tract. Notwithstanding, neuroprotective and gastroprotective effects of Ginkgo biloba supplements (GBS) have been investigated independently. Hence, whether GBS-mediated GIT-protective capacity could be helpful in PD via gut-brain anti-inflammatory signaling still remains unknown. Treatment with GBS significantly repressed the motor behavioral and neuromuscular deficits and prevented loss of striatal dopaminergic loss by improving the level of tyrosine hydroxylase enzyme and suppressing synucleinopathy development. Striatal neurons and ileal epithelial injury following intraperitoneal rotenone administration were accompanied with oxidoinflammatory/nitroinflammatory stress and marked inhibition of cholinergic transmission. Moreover, there was increased striatal executioner caspase-3 and decreased nuclear factor erythroid-2-related factor 2 (Nrf2) immunoexpression, loss of striatal pyramidal neuron with a marked decrease in length and width of the dendritic spines as well as significant hyperplasia of cryptal cells in the ileal epithelial tissues, all which were reversed by the pretreatment + concurrent (Pre-CONC) and concurrent (CONC) GBS treatment pattern. In sum, we proved the potential dual effects of GBS in preventing both dopaminergic neural-related impairments and gut wall abnormalities linked with PD.

Kolaviron, a flavonoid-rich extract ameliorates busulfan-induced chemo-brain and testicular damage in male rats through inhibition of oxidative stress, inflammatory, and apoptotic pathways.

Previous reports revealed that increased oxidative stress with up-regulated inflammatory proteins and apoptotic factors have serious implications in busulfan-induced chemo-brain and testicular damages. Hence, we investigated the potential reversal effects of kolaviron (KV), a neuro-active extract rich in flavonoids with proven anti-oxido-inflammatory and anti-apoptotic properties, on busulfan-induced oxidative damage, inflammatory proteins, and apoptosis in the brains and testes of male rats. In the treatment-regimen, animals in groups 1 and 2 had saline (10 ml/kg/p.o./day) and dimethyl sulfoxide (DMSO; 10 ml/kg/p.o./day), group 3 received KV extract (200 mg/kg/p.o./day), group 4 was given busulfan (50 mg/kg/p.o./day) and animals in group 5 were pretreated with busulfan (50 mg/kg/p.o./day) successively for 56 days in addition to KV extract (200 mg/kg/p.o./day) from days 29-56. Non-spatial memory function was valuated with a novel-object recognition memory test. Thereafter, testicular and brain oxidative/antioxidant status, proinflammatory- and apoptotic-related proteins, testicular enzymatic markers were evaluated respectively. Kolaviron extract improved cognitive function by increasing exploration of novel-object of busulfan-treated rats. Kolaviron extract reversed busulfan-mediated increased malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and decreased superoxide dismutase, catalase, glutathione, and glutathione-peroxidase in brains and testes as well as the testicular enzyme markers. Increased brain and testicular weights, and TNF-α, IL-1ß, and NF-κß productions due to busulfan administration were also reduced by the extract. The reduced testicular B-cell lymphoma-2, sperm mitochondrial cytochrome-C, and membrane potential, increased DNA fragmentation, caspases -3 and -9 levels were also profoundly reversed by KV. Additionally, KV extract ameliorated busulfan-induced testicular histopathological changes in rats. Conclusively, KV extract reverses busulfan-induced neuroendopathobiological derangements via oxidative stress inhibition, down-regulation of inflammatory and apoptotic mediators in rats' brains and testes. PRACTICAL APPLICATIONS: Busulfan is an orally effective chemotherapy drug widely used for cancer treatment. It has been reported that chronic usage of busulfan increases the tendency for carcinogenic and teratogenic activities with severe side effects on the functions of the gonads and other body organs such as brain, popularly regarded as chemo-brain. When taken over a prolonged period of time, busulfan causes sterility in animals and destroyed spermatogonial stem cells along with the seminiferous tubules and sperm morphology of animals as well as memory impairments. The findings from the study revealed that KV extract prevent busulfan-induced cognitive and testicular impairments following kolaviron supplementation. Thus, the findings from this scientific investigation suggest that KV extract could improve the quality of reproductive life and cognitive functions of male patients during busulfan chemotherapy, particularly during prolonged therapy.

Lead acetate induces hippocampal pyramidal neuron degeneration in mice via up-regulation of executioner caspase-3, oxido-inflammatory stress expression and decreased BDNF and cholinergic activity: Reversal effects of Gingko biloba supplement.

PURPOSE: It has been hypothesized that compounds with strong anti-oxidant activity might mitigate lead-induced neurotoxicity that resulted to neuronal degeneration.Ginkgo biloba supplement (GB-S) is a neuroactive supplement which has been reported to demonstrate neuroprotective effects. In this study, we investigated the reversal effect and the underlying mechanism of GB-S following lead-induced neurotoxicity in mice. METHODS: Male Swiss mice (n = 8) were pre-treated with lead acetate (100 mg/kg) for 30 min before GB-S (10 mg/kg and 20 mg/kg) or Ethylenediaminetetraacetic acid (EDTA) (50 mg/kg) intraperitoneally for 14 consecutive days. Memory impairment symptoms were evaluated on day 13 and 14 using Y-maze and Novel object recognition test (NORT) respectively. Thereafter, spectrophotometry, ELISA, immunohistochemistry and histomorphormetry were used to estimate the degree and expression of biomarkers of neuronal inflammation: oxido-inflammatory stress, apoptosis and degeneration in the hippocampus (HC). RESULTS: Lead acetate treatment significantly (p < 0.05) induced neurobehavioral impairment which was reversed by GB-S as evident in increased percentage alternation and discrimination index. GB-S significantly (p < 0.05) reduced lipid peroxidation and nitrite level, inhibited TNF-α and acetylcholinesterase activity and improved glutathione, catalase and superoxide dismutase activity in the HC. Moreover, GB-S inhibited hippocampal apoptosis via elevated expression of caspase-3 with marked increase level of brain derived neurotrophic factor (BDNF). Also, the histomorphormetric study showed that GB-S rescued death of pyramidal neurons (CA3) in the HC. CONCLUSION: Our findings however suggest that GB-S decreased memory impairment progression induced by lead acetate via mechanisms connected to inhibition of oxido-inflammatory stress mediators, restrained acetylcholinesterase activity, up-regulated BDNF/Caspase-3 expression and suppression of hippocampal pyramidal neuron degeneration in mice.

Plukenetia conophora seed oil ameliorates streptozotocin-induced hyperglycaemia and oxidative stress in rats.

PURPOSE: Plukenetia conophora (African walnut) is an edible seed, widely cultivated for its ethnomedicinal and nutritional purposes. Consumption of African walnuts has been linked with blood sugar lowering effect. OBJECTIVE: The effects of P. conophora seed oil treatment on hyperglycaemia and oxidative stress were investigated in plasma, liver and kidney of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Plukenetia conophora seed oil (PCO) was obtained by extraction of pulverized dried seed in n-hexane. Diabetes was induced by STZ injection (65 mg/kg, i.p). Rats were assigned into non-diabetic control (NC) and diabetic control (DC; treated with vehicle), PCO (200 mg/kg) and pioglitazone (10 mg/kg). Fasting blood sugar (FBS) was taken from overnight fasted animals on day 7 and 14, respectively. Plasma, liver and kidney samples were obtained on day 14 for the determination of oxidative stress parameters malondialdehyde (MDA), reduced glutathione (GSH), catalase and superoxide dismutase (SOD). RESULTS: PCO treatment significantly (p < 0.05) reduced STZ-induced hyperglycaemia by lowering the elevated FBS. PCO significantly reduced MDA level and attenuated STZ-induced depletion of GSH, catalase and SOD in the diabetic rats' plasma, liver and kidneys. CONCLUSIONS: These results suggest that consumption of Plukenetia conophora seed might offer protection against diabetes-induced hepatic and renal damage.

Gingko biloba abrogate lead-induced neurodegeneration in mice hippocampus: involvement of NF-κB expression, myeloperoxidase activity and pro-inflammatory mediators.

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.

Involvement of striatal oxido-inflammatory, nitrosative and decreased cholinergic activity in neurobehavioral alteration in adult rat model with oral co-exposure to erythrosine and tartrazine.

Overuse or overconsumption of food additive or colorant cannot be ignored in our society and there are several reports of it harmful effect on the body system. This study investigated the toxicity effect of tartrazine and erythrosine (ET, 50:50) on neurobehavioral alteration, striatal oxido-nitrosative and pro-inflammatory stress and striatal acetylcholinesterase activity in experimental rat model. Rats were co-exposed to ET (2 mg/kg, 6 mg/kg and 10 mg/kg) and distilled water (control), p.o for 6 weeks. The change in neurobehavioral function (Open field test, Forced swimming test and Tail suspension test), Lipid peroxidation (Malonaldehyde, MDA), Antioxidants (Glutathione, GSH; Catalase, CAT) Nitrite, Pro-inflammatory cytokine (Tumor necrosis factor-alpha, TNF-α) and Acetylcholinesterase (AChE) activity were evaluated. Results showed significant decrease in neurobehavioral functions after co-exposure to ET. Moreover, there were significant increase in MDA and Nitrite level, significant decrease in the concentration of GSH and CAT and a significant increase TNF-α concentration and AChE activity after co-exposure to ET. Oral co-exposure to tartrazine and erythrosine induced decrease in locomotion and exploration, increase anxiety and depression-like behavior and altered the cholinergic system through upregulation of oxido-nitrosative stress, pro-inflammatory cytokine and acetylcholinesterase activity.

Anti-diabetogenic and in vivo antioxidant activity of ethanol extract of Dryopteris dilatata in alloxan-induced male Wistar rats.

AIMS: Oxido-inflammatory stress has been implicated as the main targets in alleviating diabetic complications induced by hyperglycaemia. Dryopteris dilatata: a bioactive plant serves great medicinal benefits in ethnopharmacology to ameliorate pathological conditions. This study investigated the protective effects of ethanol extract of Dryopteris dilatata (EEDD) in alloxan-induced diabetic rats through mechanism involving inhibition of oxidative stress and liver and kidney inflammatory markers. METHODOLOGY: Male Wistar rats were made diabetic via alloxan monohydrate (100 mg/kg) administration intraperitoneally. Diabetic rats were post-treated with EEDD (800 mg/kg) and Metformin (50 mg/kg) orally for two weeks. Fasting blood sugar (FBS), body and organ weight change, markers of oxidative stress, liver and kidney inflammation were evaluated. RESULTS: Our results revealed that EEDD significantly reduced alloxan-induced hyperglycaemia in the diabetic rats after 5, 10 and 15 days of treatment. Markers of oxidative injury were also significantly ameliorated in the pancreas, liver and kidney of the diabetic rats following treatment with EEDD. However, liver and kidney injury markers were significantly attenuated with marked decreased organ weight in the diabetic rats after treatment with EEDD. CONCLUSION: Here in, we found that Dryopteris dilatata could be used as nutraceuticals in the prevention and treatment of diabetes and its related complications through positively modulating oxidative stress and liver and kidney inflammatory markers.

Moringa oleifera-supplemented diet protect against cortico-hippocampal neuronal degeneration in scopolamine-induced spatial memory deficit in mice: role of oxido-inflammatory and cholinergic neurotransmission pathway.

The therapeutic and pharmacological management of Alzheimer's disease (AD) is generally considered a major concern in ethnomedicine. Moreover, plant-based foods containing flavonoids were previously reported to show neuroprotective effects by modulating self-aggregation of amyloid-ß (Aß)/or tau peptide into oligomers and fibrils, associated with the pathogenesis of AD. This study investigated the impact of Moringa oleifera-supplemented diet (MO-SD) in scopolamine-induced spatial memory deficit in mice. Mice were partitioned into two phases with five groups each (n=6) and pretreated intraperitoneally with scopolamine (1 mg/kg) prior the daily oral administration of MO-SD (1 %, 5 % and 10 %) for 7 and 14 days. Spatial memory function was assessed using the Morris water maze (MWM) test. Thereafter, markers of cholinergic system inhibition (Acetylcholinesterase; AChE) and oxido-inflammatory stress (Malonaldehyde, MDA; Nitrite; Superoxide Dismutase, SOD; Tumor necrosis factor-alpha, TNF-α) and histo-morphology of the cortico-hippocampal neuron were measured. The scopolamine treatment led to loss of spatial memory function in mice spatial exploration of the escape platform in the MWM test. Meanwhile, treatment with MO-SD attenuated loss of spatial memory function via significant decrease in escape latency, significant increase in the frequency of cross with time spent in the platform quadrant. Furthermore, scopolamine treatment altered the endogenous antioxidants and pro-inflammatory mediators, elevated acetylcholinesterase activity and promoted chromatolysis of the cortico-hippocampal neuron. However, MO-SD significantly ameliorated oxido-inflammatory stress, restored cholinergic transmission via acetylcholinesterase inhibition and maintains neuronal integrity in the mice brain at both phases. These results suggest that Moringa oleifera-supplemented diet may serve a potential therapeutic and possible pharmacological macromolecule for preventing loss of neuronal cells and management of Alzheimer's disease.

Kolaviron abates busulfan-induced episodic memory deficit and testicular dysfunction in rats: The implications for neuroendopathobiological changes during chemotherapy.

Busulfan is a popular antileukemia chemotherapeutic alkylating agent widely known to induce variety of serious adverse effects including chemobrain-related cognitive impairments and dysfunction in male reproductive system. Whether kolaviron, a neuro- and repro-active compound obtained from Garcinia kola, with neuroprotective and reproductive-promoting activities, mitigates busulfan-induced cognitive and male reproductive impairments remain unknown. Hence, we investigated the reversal effects of kolaviron on busulfan-induced episodic memory deficit and testicular dysfunction, and its underlying mechanisms in male rats. In the treatment-protocol, rats in groups 1 and 2 received saline (10 mL/kg/p.o./day) and DMSO (10 mL/kg/p.o./day) respectively, group 3 was given kolaviron (200 mg/kg/p.o./day), group 4 received busulfan (50 mg/kg/p.o./day) and group 5 was pretreated with busulfan (50 mg/kg/p.o./day) consecutively for 56 days prior to kolaviron treatment (200 mg/kg/p.o./day) from days 29-56. Episodic memory deficit was assessed using passive avoidance task (PAT). Following euthanization, blood samples, epididymal sperm, testes and brain were harvested and hormonal and neurochemical contents and their metabolizing enzymes were assayed. Kolaviron reversed busulfan-induced episodic cognitive deficit in the PAT. The reduced serotonin, dopamine, noradrenaline concentrations, elevated glutamate levels, acetylcholinesterase, monoamine oxidase-A and B activities were normalized by kolaviron. Kolaviron also reversed the busulfan-induced decreased testicular/body weights and spermatogenesis. Kolaviron abated busulfan-induced changes in androgenic hormones (testosterone, FSH, LH), dehydrogenase enzymes (3ß-HSD and 17ß-HSD), altered sperm-chromatin, sperm-membrane integrity and sperm-acrosomal reaction and capacitation impairments. Our findings suggest that kolaviron could mitigate busulfan-induced episodic memory deficit and dysfunction in male reproductive system via neurochemical modulations and increase testicular androgenic hormones/enzymes in rats.

Long-term consumption of Moringa oleifera-supplemented diet enhanced neurocognition, suppressed oxidative stress, acetylcholinesterase activity and neuronal degeneration in rat's hippocampus.

OBJECTIVES: This study investigates protection against oxidative stress and memory enhancing potential of long-term consumption of Moringa oleifera leaves. METHODS: Male Wistar rat were fed with mixture of M. oleifera-supplemented diets (MOSD) partitioned in 1, 5, 10, and 20% continuously for 12 weeks. Object recognition test (ORT) and Morris water maze (MWM) was used for assessing neurocognition. Changes in body weight, Lipid peroxidation (MDA), Glutathione (GSH), Catalase (CAT) and Acetylcholinesterase (AChE) activity was assayed in the brain tissue. Histomorphometric of the hippocampus was also examined. RESULTS: The diets progressively increase the body weigh after the 12 weeks, improved spatial (MWM) and non-spatial (ORT) memory performance, protect against oxidative stress, inhibit AChE activity and suppresses neuronal degeneration in the hippocampus when stained with Cresyl violent stain. CONCLUSIONS: Conclusively, long-term consumption of MOSD shows strong protection against oxidative stress and hippocampal degeneration and improves neurocognition with dose dependent effect.