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.

Cannabis sativa exacerbate testicular function by increased oxidative stress, altered male reproductive hormones, sperm quality/quantity and cellular architecture of the testis.

The illicit use of Cannabis in Nigeria is on the increase within the last 10 years and has been implicated as one of the causes of fertility disorder among young men in Nigeria. Hence, this study aimed to ascertain the reproductive impact of n-hexane extract of Cannabis sativa on male Wistar rats. Fifteen male Wistar rats weighing between 180 and 200 g were assigned into three groups of five animals each. The first group served as control, second (low dose), and third (high dose) were fed with n-hexane extract of C. Sativa at doses of 0.75 mg/100 g and 1.5 mg/100 g body weight respectively for 28 days. The administration was done via orogastric. The results revealed the mean serum gonadotropin-releasing hormone (GnRH) concentration in LD and HD was significantly lower (p < 0.05) than in control. LH was significantly higher (p < 0.01) in both LD and HD compared to control. There was a significant increase (p < 0.01) in LD and HD compared to control. Testosterone was significantly elevated in HD (p < 0.05) compared to control. Testicular reduced glutathione and Superoxide dismutase were significantly (p < 0.05) reduced in fed rats compared to control. Testicular catalase and Malondialdehyde were significantly (p < 0.05) increased in HD compared to control. Non-motile sperm count showed a significant (p < 0.001) increase in fed rats compared to control. Total sperm count was significantly (p < 0.05) reduced in fed rats than in control. There were significant (p < 0.001) increased spermatozoa with abnormal morphology in treated groups compared to control. HDL cholesterol was significantly (p < 0.05) elevated in HD compared to control. The atherogenic index was significantly (p < 0.05) reduced in the group fed with 1.5 mg/kg compared to the control. Furthermore, total cholesterol, triglyceride, VLDL-c, and LDL-c did not reveal any significant difference statistically. Histological examination of testes and epididymis of fed rats showed an empty cavity with a reduction in spermatogenesis. This study suggests that n-hexane extract of C. Sativa had more effects on the gonads compared to the higher centres and its ingestion in whatever form could impair male reproductive function.

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.

Inhibition of human androgen receptor by delta 9-tetrahydro-cannabinol and cannabidiol related to reproductive dysfunction: A computational study.

There have been conflicting reports on the impact of Cannabis sativa impact on reproductive function. Hence this study was aimed to ascertain the impact of tetrahydrocannabinol (THC) and cannabidiol (CBD) binding affinity on human androgen receptor (AR) via computational molecular dynamic simulation. The human AR coordinate in this study is derived from human AR in complex with the ligand metribolone (R18) (PBD ID: 1E3G) template using (MODELER version. 9.15). CBD (PubChem CID: 644019), and THC (PubChem CID: 16078) 2D structures were retrieved from PubChem and docked (Autodock-Vina inbuilt in PyMol into the active site of human AR using the coordinates of the co-crystalized ligand (R18). All atomic representations in this study were created using visual molecular dynamics (VMD) tools. The result revealed that neither CBD nor THC bear significant 2D similarity with R18. Despite the diversity within the chemical space, both CBD and THC poses bond flexibility required to bind avidly to AR with the docking scores comparable to R18. In fully bound state, the three compounds engage the AR pocket hydrophobic residues such as L701, L704, and L707, and aromatic residues such as F764. Polar contacts with T877 observed in R18 bound state is avoided in the THC and CBD bound states. Moreso, the results revealed that CBD has lesser binding energy compared to THC and R18 compound which serves as standard. This study hypothesized that CBD and THC binds complimentarily to the pocket AR, indicating a likely inhibition of reproductive function and prostate cancer progression.

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.

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.

Selenium abates manganese-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats.

Excessive exposure to manganese (Mn) is associated with neurotoxicity characterized by oxidative stress, inflammation, and apoptosis induction. Selenium (Se) has been shown to possess antioxidant, anti-inflammatory, and anti-apoptotic properties in humans and animals. The present study investigated the neuroprotective mechanism of Se in rats sub-chronically treated with Mn at 30 mg/kg body weight or orally co-treated with Se at 0.2 and 0.4 mg/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were recorded and computed with the aid of ANY-Maze (a video-tracking software) for 5-min trial, in a novel apparatus. The ANY-Maze analysis showed that Se significantly (p < 0.05) abated Mn-induced locomotive impairment evidenced by increased in maximum speed, total time traveled, absolute turn angle, number of line crossing, rotation and forelimb grip and decreased total time immobile, grooming, and negative geotaxis as verified by the enhanced track plot density. Furthermore, the striatum and hippocampus of the rats were excised and the levels of Mn and Se, oxidative stress markers, proinflammatory cytokines including acetylcholinesterase and caspase-3 activities were assayed. The result shows that Se abates Mn-mediated accumulation of Mn. Also, Se ameliorated Mn-induced decrease in antioxidant enzymes as well as glutathione level and increase in acetylcholinesterase activity, lipid peroxidation, proinflammatory cytokines (i.e., interleukin (IL)-6, IL-1ß, tumor necrosis factor alpha), and caspase-3 activation in the striatum and hippocampus of the rats. Collectively, Se abated Mn-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats. Se may serve as a neuroprotective agent against Mn-mediated neurotoxicity.

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.

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.

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.

Anxiogenic and memory impairment effect of food color exposure: upregulation of oxido-neuroinflammatory markers and acetyl-cholinestrase activity in the prefrontal cortex and hippocampus.

Erythrosine and tartrazine are one of the synthetic azo dye mostly consumed in food, drugs and other industrial compounds. This study was designed to investigate the adverse effect of combine erythrosine and tartrazine on cognitive and neurobehavioral functions, pro-oxidants, endogenous antioxidants, cholinergic system and pro-inflammatory cytokines in rats. Erythrosine and tartrazine (2 mg/kg, 6 mg/kg, and 10 mg/kg, b.w., p.o, 50:50) was administered to rats (n = 6) for 6 weeks. Memory and neurobehavioral assessment using Novel object recognition test (NORT) and Elevated plus maze (EPM) and biochemical (pro-oxidants and anti-oxidant enzymes) and pro-inflammatory cytokine measurement from the brain sub regions namely, hippocampus and prefrontal cortex were done at the end of treatment. The results showed (p < 0.05) significant decreased memory and neurobehavioral function, increased acetyl-cholinesterase and pro-oxidants activity (Malonaldehyde level and Nitrite), decreased endogenous anti-oxidants (Glutathione and Catalase) and increased pro-inflammatory cytokines (Tumor necrosis factor-alpha, TNF-α). We suggested that the mechanism by which this oxidative and neuro-inflammatory damage and cholinergic system alteration occur might be related to the release of metabolite in fission of the azo dyes of the combined erythrosine and tartrazine administration in the animals. However, we concluded on these findings that erythrosine and tartrazine dyes significantly provoke the release of oxido-nitrergic and neuroinflammatory stress markers and also may incite acetyl-cholinesterase activities in different brain regions leading to memory and neurobehavioral impairment.

Synthetic Food dyes cause testicular damage via up-regulation of pro-inflammatory cytokines and down-regulation of FSH-R and TESK-1 gene expression.

OBJECTIVE: This study investigated the effects of Tartrazine and Erythrosine (T+E) on the reproductive hormones and expression of some pro-inflammatory cytokines and testicular genes in testis of male Wistar rats. METHODS: 25 male Wistar rats (150-180g) were divided into 5 groups (n=5). Group 1 received distilled water while groups 2, 3, 4 and 5 were treated with T+E (2.5mg/kg, 5mg/kg, 10mg/kg and 20mg/kg) for the period of 23 days. Toxicity studies of the combined dye were investigated by evaluating serum reproductive hormones [Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Testosterone], gene expression and profiling, and testes histology. RESULTS: male Wistar rats (150-180g) were divided into 5 groups (n=5). Group 1 received distilled water while groups 2, 3, 4 and 5 were treated with T+E (2.5mg/kg, 5mg/kg, 10mg/kg and 20mg/kg) for the period of 23 days. Toxicity studies of the combined dye were investigated by evaluating serum reproductive hormones [Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Testosterone], gene expression and profiling, and testes histology. CONCLUSIONS: This present study reveals that the dyes could impair testicular function as evident in the up-regulation of pro-inflammatory cytokines and down-regulation of TESK-1 gene expression and architecture of the testes leading to Orchitis.