Neuroprotective potential of plant derived parenchymal stem cells extract on environmental and genetic models of Parkinson disease through attenuation of oxidative stress and neuroinflammation.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor features. The current treatment regimen for PD are dopamine enhancers which have been reported to worsen the disease prognosis after long term treatment, thus, the need for better treatment options. This study sought to investigate the protective action of Double Stem Cell® (DSC), a blend of stem cells extracts from Swiss apples (Malus Domestica) and Burgundy grapes (Vitis vinifera) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in mice and genetic model of PD in Drosophila melanogaster. Male albino mice were pretreated with MPTP (4 × 20 mg/kg, i.p., two hourly in 8 h), twelve hours before administration of DSC (8, 40, or 200 mg/kg, p.o.). Thereafter, behavioural, biochemical and immunohistochemical assays were carried out. The impact of vehicle or DSC supplementation on α-synuclein aggregation was evaluated in Drosophila melanogaster using the UAS-Gal4 system, female DDC-Gal4 flies were crossed with male UAS-α-synuclein, the progenies were examined for fecundity, locomotion, memory, and lifespan. MPTP-induced motor deficits in open field test (OFT), working memory impairment (Y-maze test (YMT)) and muscle incoordination (rotarod test) were ameliorated by DSC (8, 40 or 200 mg/kg) through dose-dependent and significant improvements in motor, cognitive and motor coordination. Moreso, MPTP exposure caused significant increase in lipid peroxidation and decrease in antioxidant enzymes activities (glutathione, catalase and superoxide dismutase) in the midbrain which were attenuated by DSC. MPTP-induced expression of microglia (iba-1), astrocytes (glia fibrillary acidic protein; GFAP) as well as degeneration of dopamine neurons (tyrosine hydroxylase positive neurons) in the substantia nigra (SN) were reversed by DSC. Supplementation of flies feed with graded concentration of DSC (0.8, 4 or 20 mg/ml) did not affect fecundity but improved climbing activity and lifespan. Findings from this study showed that Double Stem Cell improved motor and cognitive functions in both mice and Drosophila through attenuation of neurotoxin-induced oxidative stress and neuroinflammation.

Antinociceptive and anti-arthritic effects of aqueous whole plant extract of Trianthema portulacastrum in rodents: Possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Trianthema portulacastrum L. (Aizoaceae) is used in traditional African Medicine for the treatment of various illnesses including dropsy, inflammation and rheumatism. AIM OF THE STUDY: This study was designed to investigate the anti-nociceptive and anti-arthritic properties of the aqueous whole plant extract of Trianthema portulacastrum (AETP), possible mechanisms of action and characterize some of the active constituents. MATERIALS AND METHODS: Antinociceptive activity was evaluated using the acetic acid-induced writhing and hot plate tests in mice. The carrageenan test was used to induce a transient inflammation while arthritis was induced with complete Freund's adjuvant (CFA) in rats. On completion of CFA-induced arthritis macroscopic observations, the rats were euthanized to isolate the spleen, liver and limbs for estimation of oxidative stress and histological analysis. RESULTS: AETP (10, 50, or 250 mg/kg; p.o.) produced significant (p < 0.05) and dose-dependent inhibition (41.10, 50.40, and 67.10%, respectively) of writhing response elicited by acetic acid. Also, increased pain threshold of supraspinally mediated nociceptive behaviour, with peak maximum possible effect (MPE) obtained at 250 mg/kg (22.98%; 30 min post-treatment). However, the pre-treatment of mice with Nitro-L-arginine (L-NNA) or naloxone reversed AETP-induced antinociception. In another experiment, AETP produced time course inhibition of carrageenan-induced paw oedema with peak effect (50.60%) at 250 mg/kg as well as significant reduction in CFA-induced arthritis by 58.56%, on day 27 and arthritic index (26.84%). Similarly, AETP attenuated CFA-induced MDA generation and deficit in antioxidant enzyme activities. Histological analysis of rat joints revealed a reduction in the synovial hyperplasia and mononuclear infiltration induced by CFA in AETP treated groups. CONCLUSION: Findings from this study showed that T. portulacastrum possesses anti-nociceptive action through nitrergic and opioidergic signalling as well as anti-arthritic effect through enhancement of antioxidant defense system and inhibition of release or actions of inflammatory mediators.

Involvement of Antioxidant System in the Amelioration of Scopolamine-Induced Memory Impairment by Grains of Paradise (Aframomum melegueta K. Schum.) Extract.

Background: Grains of paradise (Aframomum melegueta) K. Schum is used to flavour foods and used as memory enhancer and anti-aging in traditional African medicine. This study examine the influence of ethanolic seed extract of Aframomum melegueta (AFM) on cognitive impairment induced by scopolamine in rodents. Methods: AFM (6.25, 12.5 or 25 mg/kg, p.o.) or tacrine (5 mg/kg, i.p.) was administered for 3 consecutive days, 1 h post-treatment on day 3, scopolamine (3 mg/kg, i.p.) was given, 5 min later, cognition was evaluated in the Y-maze and elevated plus maze (EPM) tests in mice as well as the Morris water maze (MWM) paradigm in rats. Biomarkers of oxidative stress in the prefrontal cortex, striatum and hippocampus of rats were evaluated after the MWM task. The antioxidant capacity of AFM was evaluated in vitro using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric ion reducing power (FRAP) assays. Results: Scopolamine significantly reduced (38.72%) spontaneous alternation behavior in the Y-maze and increase in transfer latency in the EPM test on day 2, which was ameliorated by AFM (25 mg/kg; 49.86%, 71.55%, respectively) in mice. In addition, AFM prevented the spatial learning deficit induced by scopolamine in the MWM task. Similarly, scopolamine-induced oxidative-nitrosative stress was attenuated by AFM treatment, evidenced in decreased malondialdehyde and nitrite levels, restoration of glutathione and superoxide dismutase levels. Interestingly, AFM exhibited notable scavenging activities against DPPH, NO and FRAP radicals. Conclusion: These results showed that A. melegueta seed extract prevented scopolamine-induced memory impairments through enhancement of antioxidant defense systems.

Antidepressant Effect of Cnestis ferruginea Vahl ex DC (Connaraceae): Involvement of Cholinergic, Monoaminergic and L-arginine-nitric Oxide Pathways.

BACKGROUND: We have previously reported antidepressant effect of Cnestis ferruginea (CF) in behavioral models of depression. Due to the promise shown by this extract, this study was carried out to investigate the contribution of monoaminergic, cholinergic and nitrergic systems to the antidepressant-like effect elicited by CF. METHODS: Male albino mice were pretreated with monoaminergic or cholinergic receptor antagonists, L-arginine or N(G)-nitro-L-arginine (nitric oxide synthase inhibitor) (at doses reported to block the in vivo effect of the agonists), 15 min before oral administration of CF (100 mg/kg), 1 h later, the forced swim test (FST) in mice was carried out. RESULTS: CF treatment produced significant changes in the duration of swimming (F(5,42)=9.86, P<0.001), climbing behaviour (F(5,42)=4.51, P=0.004) and mean time spent immobile (F(5,42)=11.55, P<0.001) vs. vehicle-treated control. Co-administration of CF with fluoxetine or imipramine potentiated their effect. However, pretreatment of mice with reserpine (F(1,16)=119.20, P<0.001), prazosin (F(1,16)=68.98, P<0.001), sulpiride (F(1,16)=15.46, P<0.01), RS 127445 ((F(1,20)=8.22, P<0.01), SB 399885 ((F(1,20)=38.44, P<0.001), atropine (F(1,16)=53.77, P<0.001), or L-arginine (nitric oxide precursor) (F(1,16)=10.35, P<0.01) prevented CF-induced antidepressant-like effect in mice. In addition, pretreatment of mice with L-NNA (10 mg/kg) augmented the effect of CF. CONCLUSION: C. ferruginea exerts its antidepressant-like action through interaction with α-adrenoceptor, dopamine D2, 5-HT2B, 5-HT6 and muscarinic cholinergi1c receptors as well as L-arginine-nitric oxide systems. C. ferruginea could be used as adjuvant with conventional antidepressants in the treatment of major depressive disorder.

Antidepressant and anxiolytic effects of the methanol root extract of Capparis thonningii: involvement of monoaminergic, cholinergic and GABAergic systems.

BACKGROUND: Capparis thonningii Schum. (Capparaceae) is used in traditional African Medicine for the treatment of mood disorders. OBJECTIVE: The study investigates antidepressant and anxiolytic activities of methanol root extract of C. thonningii (CT). METHODS: CT (25-100 mg/kg, p. o.) was administered 1 h before behavioral studies were carried out in mice. Antidepressant effect was investigated using the forced swimming test (FST) and tail suspension test (TST). The anxiolytic effect was evaluated using the elevated-plus maze test (EPM), hole-board test (HBT), and light-dark test. RESULTS: CT (25 and 50 mg/kg) increased swimming activity (P<0.05) by 92.73% and attenuated immobility time by 35.72%, similar to anti-immobility effect of imipramine (33.87%) in FST. In addition, CT (50 mg/kg) significantly (P<0.01) reduced immobility time by 30.24% in TST. -However, the antidepressant-like effect elicited by CT was reversed by metergoline, cyproheptadine, and sulpiride (40.81, 45.93, and 48.52%, respectively) pretreatment but prazosin, and yohimbine failed to reverse this antidepressant-like effect. Similar to diazepam, CT (25 mg/kg) increased duration of open arms exploration (P<0.05) by 43.73% in EPM, number of head-dips (HBT) (90.32%), and time spent in the light compartment by 45.77% in light/dark test indicating anxiolytic-like effect. The anxiolytic-like effect of CT was reversed by flumazenil pretreatment. CONCLUSION: The findings from this study suggest antidepressant-like effect of C. thonningii involving interaction with serotonergic (5-HT2), dopaminergic (D2), noradrenergic (α1 and α2), and muscarinic cholinergic systems; and anxiolytic effect through an interaction with GABAA benzodiazepine receptor.

Hepatoprotective and antioxidant activities of Hepacare®, a herbal formulation against carbon tetrachloride-induced liver injury.

BACKGROUND: Hepacare(®) is a herbal formulation used to treat patients with sickle-cell anaemia complicated with jaundice, also recommended as a protective agent against liver damage due to chronic ingestion of alcohol. METHODS: In vitro antioxidant properties of Hepacare(®) was determined using 1, 1- diphenyl-2-picryl-hydrazyl (DPPH), total antioxidant capacity, reducing power ability, and nitric oxide assays. Hepatoprotective effect of Hepacare(®) (50-400 mg/kg/day for 7 days, p.o.) was investigated in male Sprague Dawley rats against carbon tetrachloride (CCl(4) /olive oil, 1:1, 0.7 ml/kg, i.p.)-induced liver damage. At the end of the study, blood samples and liver tissue were assayed for biochemical and antioxidants parameters. RESULTS: Hepacare produced concentration dependent inhibition of DPPH and nitric oxide activity with IC(50) of 48.50 and 55.00 µg/ml, respectively, it suppressed the absorbance of ABTS(.+) with total antioxidant capacity of 423.47±8.37 mg QUE/g. CCl(4) administration induced significant (P<0.001) elevation of serum aspartate transaminase (1.70 fold), alanine transaminase (1.60 fold), alkaline phosphatase (2.90 fold) and bilirubin (2.00 fold) in comparison to control. The increase in serum biomarker were dose-depen-dently reversed by Hepacare(®) pretreatment. More-over, CCl(4) pretreatment increased (P<0.001) malondialdehyde (MDA) (73.98%) and decreased (P<0.001) antioxidant enzymes level but Hepacare pretreatment produced dose-dependent attenuation of the increased MDA (3.84 fold) with enhancement of glutathione (3.08 fold), superoxide dismutase (2.08 fold), and catalase (3.14 folds) levels in comparison to CCl(4) treated group, similar to those of silymarin reference standard. CONCLUSION: Hepacare was beneficial in the prevention of CCl(4)-induced hepatocellular injury, possibly by scavenging reactive free radicals, and boosting endogenous antioxidant systems.

Antidepressant and anxiolytic properties of the methanolic extract of Momordica charantia Linn (Cucurbitaceae) and its mechanism of action.

BACKGROUND: The whole plant of Momordica charantia Linn (Cucurbitaceae) is used in traditional African medicine in the management of depressive illness. METHODS: Momordica charantia (MC) (50-400 mg/kg, p.o.) was administered 1 h before behavioural studies using the forced swimming test (FST) and tail suspension test (TST) to investigate antidepressant-like effect while the anxiolytic-like effect was evaluated with elevated plus maze test (EPM), hole-board test (HBT), and light-dark test (LDT). RESULTS: Acute treatment with MC (50-400 mg/kg) significantly increased swimming time (86.51%) and reduced the duration of immobility (52.35%) in FST and TST with peak effects observed at 200 mg/kg, respectively, in comparison to control. The pretreatment of mice with either sulpiride (dopamine D2 receptor antagonist), or metergoline (5-HT2 receptor antagonist), or cyproheptadine (5-HT2 receptor antagonist), or prazosin (α1-adrenoceptor antagonist), or yohimbine (α2-adrenoceptor antagonist), and atropine (muscarinic cholinergic receptor antagonist) 15 min before oral administration of MC (200 mg/kg) significantly blocked its anti-immobility effect. Similarly, MC (200 mg/kg) significantly reduced anxiety by increasing the open arm exploration (64.27%) in EPM, number of head-dips in HBT (34.38%), and time spent in light compartment (29.38%) in the LDT. However, pretreatment with flumazenil (GABAA receptor antagonist) 15 min before MC (200 mg/kg) significantly blocked (54.76%) its anxiolytic effect. CONCLUSION: The findings in this study showed that MC possesses antidepressant-like effect that is dependent on the serotonergic (5-HT2 receptor), noradrenergic (α1- and α2-adrenoceptors), dopaminergic (D2 receptor), and muscarinic cholinergic systems and an anxiolytic-like effect that might involve an action on benzodiazepine-type receptor.

Evaluation of amentoflavone isolated from Cnestis ferruginea Vahl ex DC (Connaraceae) on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Cnestisferruginea (CF) Vahl ex DC (Connaraceae) is a shrub widely used in traditional African medicine for the treatment of various psychiatric illness and inflammatory conditions. AIM OF THE STUDY: This study was carried out to investigate the effect of amentoflavone isolated from methanolic root extract of CF on lipopolysaccharide (LPS)-induced neuroinflammatory cascade of events associated to the oxidative and nitrative stress, and TNF-α production in rat astrocytoma cell line (C6) and human monocytic leukemia cell line (THP-1), respectively. MATERIALS AND METHODS: Rat astrocytoma cells (C6) were stimulated with LPS (10µg/ml) alone and in the presence of different concentrations of amentoflavone (0.1-3µg/ml) for 24h incubation period. Nitrite release, reactive oxygen species (ROS), malondialdehyde (MDA) and reduced-glutathione (GSH) in C6 cells were estimated; while the TNF-α level was estimated in THP-1 cell lysate. In vivo analgesic activity was evaluated using mouse writhing and hot plate tests while the anti-inflammatory effect was investigated using carrageenan-induced oedema test. RESULTS: LPS (10µg/ml) significantly (P<0.05) stimulated C6 cells to release nitrite, ROS, MDA, and TNF-α generation while GSH was down regulated in comparison to control. However, amentoflavone significantly (P<0.05) attenuated nitrite, ROS, MDA and TNF-α generation and also up regulated the level of GSH. Amentoflavone per se did not have any significant effect on C6 and THP-1 cells. Amentoflavone (6.25-50mg/kg) significantly (P<0.05) reduced number of writhes and also increase pain threshold in hot plate test. It produced time course significant (P<0.05) decrease in oedema formation in rodents. DISCUSSION AND CONCLUSION: Findings in this study demonstrate the anti-neuroinflammatory and antinoceptive effects of amentoflavone which may suggest its beneficial roles in neuroinflammation associated disorders.