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.

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.

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.

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.

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.

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.

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.

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.

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.

Cnidoscolus aconitifolius-supplemented diet enhanced neurocognition, endogenous antioxidants and cholinergic system and maintains hippocampal neuronal integrity in male Wistar rats.

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 (p<0.05) improve memory performance with time-dependent effects in rats fed with CAD on MMW and NORT. MDA significantly (p<0.05) reduce in 1 and 2.5% CAD groups at 4th weeks and in 2.5 and 5% CAD groups at 8th weeks while GSH concentration significantly (p<0.05) increase at 12th weeks in 2.5 and 10% CAD groups. However, CAT concentration significantly (p<0.05) increase in 2.5, and 5%, CAD groups, 1, 5, and 10% CAD groups and in 5, and 10% CAD groups at 4th, 8th and 12th weeks. AChE significantly (p<0.05) reduce at 4th and 12th weeks. Histological assessment reveals no neuronal and pyramidal degeneration (chromatolysis) at the hippocampal Cornu 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.