ABSTRACT
Various NMDA-receptor antagonists have been investigated for their therapeutic potential in Alzheimer's disease with memantine shown to be safe and with relative efficacy. There is, however, need to develop novel drugs to counter tolerance and with better efficacy in ameliorating neurodegeneration. We have shown neurodegeneration in different models of vanadium-exposed mice. This study was designed to evaluate and ascertain the potency of three novel NMDA-receptor antagonists (Compounds A, B and C) to ameliorate neurodegeneration in vanadium-exposed mice. One-month-old mice (n = 6) received sterile water (control) and another group (n = 6) was treated with vanadium (3 mg/kg sodium metavanadate) intraperitoneally for 1 month. Three other groups (n = 6) received vanadium and compounds A, B and C (4.35 mg/kg, 30 mg/kg and 100 mg/kg, respectively) simultaneously for the same period. Assessment of pathologies and neurodegeneration in different brain regions was done to test the ameliorative effects of the 3 antagonists using different immunohistochemical markers. Vanadium exposure resulted in reduced calbindin expression and pyknosis of Purkinje cells, cell loss and destruction of apical dendrites with greater percentage of cytoplasmic vacuolations, morphological alterations characterized by cell clustering and multiple layering patterns in the Purkinje cell layer. In addition, the observed degeneration included demyelination, increased GFAP-immunoreactive cells and microgliosis. Simultaneous administration of the compounds to vanadium-exposed mice resulted in the preservation of cellular integrity in the same anatomical regions and restoration of the cells' vitality with reduced astroglial and microglial activation.
Subject(s)
Excitatory Amino Acid Antagonists/pharmacology , Nerve Degeneration , Neurotoxicity Syndromes/prevention & control , Purkinje Cells/drug effects , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Astrocytes/pathology , Calbindins/metabolism , Cell Death/drug effects , Disease Models, Animal , Glial Fibrillary Acidic Protein/metabolism , Mice , Microglia/drug effects , Microglia/metabolism , Microglia/pathology , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/pathology , Purkinje Cells/metabolism , Purkinje Cells/pathology , Receptors, N-Methyl-D-Aspartate/metabolism , VanadatesABSTRACT
BACKGROUND: Buchholzia coriacea, taken by elderly, has phytochemicals that have neuro-active metabolites, and the folklore documented its use in neuro-behavioural despairs. OBJECTIVE: This study was conducted to investigate the neuro-pharmacological potentials of Buchholzia coriacea (MEBC) seed extract in the laboratory rodents. METHODOLOGY: Methanol extract of the seeds on B. coriacea (MEBC) was evaluated for its antidepressant (Forced Swimming Test and Tail Suspension Test), anxiolytic (Light-Dark Test, Hole Board Test and Elevated Plus Maze), antinociceptive (Hot-Plate and Tail Flick test) and motor coordination (Rota Rod) functions in mice. RESULTS: Our findings showed antidepressant activity (P < 0.05) of MEBC that is dose-dependent. Secondly, MEBC showed significant anxiolytic property that is comparable with the standard drug (diazepam). Furthermore, MEBC significantly prolonged the latency on hot-plate and tail flick responses when compared with the control (P < 0.05). Finally, MEBC significantly prolonged mice endurance time (P < 0.05) on a revolving Rota rod. The results suggest antidepressant, anxiolytic and analgesic potentials of MEBC. CONCLUSION: Buchholzia coriacea may have a stabilizing effect on the motor activity and MEBC probably contains secondary metabolites with some therapeutic effects on neuro-physiological disorders like depression, anxiety and pain.
Subject(s)
Analgesics/pharmacology , Anti-Anxiety Agents/pharmacology , Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Capparaceae , Plant Extracts/pharmacology , Seeds , Animals , Anxiety , Depression , Disease Models, Animal , Male , Mice , PainABSTRACT
OBJECTIVE: To investigate the toxicity of an ethanolic extract of the aerial parts of Tithonia diversifolia, used in Nigeria to treat malaria, in rats. MATERIALS AND METHODS: A 70% ethanol extract was administered orally to adult Wistar rats at various dosages (400-1600 mg/kg) and the animals sacrificed and various organs examined at a range of times from 30 min up to 24 h after administration. RESULTS: The studies showed a dose- and time-dependent toxic effect, which was reversible on the kidney and liver while there was no noticeable adverse effect on the morphology of the heart, spleen and brain. CONCLUSION: A 70% ethanol extract of the aerial parts of Tithonia diversifolia, which had previously been shown to reduce parasitemia in mice infected with Plasmodium, displayed kidney and liver toxicity at the lowest dose tested. The use of this plant extract against malaria therefore raises concerns over its safety.
Subject(s)
Antimalarials/toxicity , Asteraceae , Kidney/drug effects , Plant Extracts/toxicity , Animals , Brain/drug effects , Cell Size/drug effects , Female , Heart/drug effects , Kidney/pathology , Leukocyte Count , Liver/drug effects , Male , Nigeria , Organ Size/drug effects , Phytotherapy , Plant Components, Aerial , Rats , Rats, Wistar , Spleen/drug effectsABSTRACT
Ethanolic extracts of the aerial part of Tithonia diversifolia and the stem bark of Crossopteryx febrifuga were investigated against early, residual (repository) and established malaria infections in vivo using Swiss albino mice at a dose range of 50-400 mg/kg per day. Chloroquine at 5 mg/kg per day was used as the positive control for the early and established infections while Pyrimethamine at 1.2 3/kg per day was used as the positive control for the residual infection test. Dose dependent chemo suppressive activities were obtained at the different levels of the infection tested. Tithonia diversifolia and Crossopteryx febrifuga gave some level of suppression of parasitaemia in the early and established infection stages. Tithonia diversifolia was active at 200 mg/kg per day in the repository test. The mean survival period of the mice treated with the extract in the established infection test was low, a possible indication of toxicity as a result of sub chronic administration of the extract. Crossopteryx febrifuga was inactive in the repository test. Beside the above limitations, the suppression of parasitaemia by the extracts at the highest dose was similar to chloroquine and pyrimathamine.
