Abstract:There is a strong association between depression and memory impairment. The present study aims to assess the nootropic activity of duloxetine and piracetam combination. Male Swiss Albino mice were divided randomly into 4 groups. Treatment of normal saline (10 ml/kg), duloxetine (10 mg/kg), piracetam (100 mg/kg), and duloxetine (5 mg/kg) plus piracetam (50 mg/kg) were given through intra-peritoneal route to group I-IV, respectively. Transfer latency in elevated plus maze (EPM) and time spent in target quadrant … Show more
“…Piracetam was administered at a dose of 300 mg/kg, while Meldonium was administered at a dose of 200 mg/kg. These doses correspond to literature data for Piracetam [87] and Meldonium [88].…”
An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the “swim exhaustion” test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.
“…Piracetam was administered at a dose of 300 mg/kg, while Meldonium was administered at a dose of 200 mg/kg. These doses correspond to literature data for Piracetam [87] and Meldonium [88].…”
An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the “swim exhaustion” test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.
“…For the control group ( N = 24), the same amount of PBS was administered in the same pattern. The dosage of piracetam was determined by referencing previous reports [[28], [29], [30]]. All of the animal handling and treatment protocols were reviewed and approved by the Animal Care and Use Committee of National Institute of Neuroscience, National Center of Neurology and Psychiatry (approval number, 2017010).…”
Background
Pelizaeus-Merzbacher disease (PMD) is caused by point mutations or copy number changes in the proteolipid protein 1 gene (
PLP1
).
PLP1
is exclusively localized in the myelin sheath of oligodendrocytes. Amino acid-substituted PLP1 protein is unable to fold properly and is subsequently degraded and/or restrictedly translated, resulting in a decrease in the PLP1 protein level and a failure to localize to the membrane. Furthermore, misfolded proteins increase the burden on the intracellular quality control system and trafficking, finally resulting in cell apoptosis. The objective of this study was to identify therapeutic chemicals for PMD by quantifying the total levels and membrane localization of PLP1.
Method
We established a cell line stably expressing PLP1
A243V
fused with green fluorescent protein in oligodendrocyte-derived MO3.13 cells. We screened a chemical library composed of drugs approved for central nervous system disorders that increased both the total intensity of PLP1
A243V
in the whole cell and the cell membrane localization. We analyzed the change in the endoplasmic reticulum (ER) stress and the gene expression of candidate chemicals using a micro-array analysis. Finally, we tested the in vivo effectiveness using myelin synthesis deficient (
msd
) mice with
Plp
A243V
.
Results and conclusion
Piracetam significantly increased the PLP1
A243V
intensity and membrane localization and decreased the ER stress. It was also shown to reverse the gene expression changes induced by PLP1
A243V
in a micro-array analysis. However, in vivo treatment of piracetam did not improve the survival of
msd
mice (Plp1
A243V
).
The aim of the current study was to analyse the augmentation of minocycline with bupropion in treating depression. 'Saline' (10 ml/kg), 'minocycline per se' (25 mg/kg), 'minocycline per se' (50 mg/kg), 'bupropion per se' (5 mg/kg), 'bupropion per se' (10 mg/kg) and 'bupropion + minocycline' (5 mg/kg + 25 mg/kg each) were administered to mice via the intraperitoneal route. In the forced swim and tail suspension test, the immobility period was analysed after 30 min of the treatment. Monoamines like dopamine, norepinephrine and serotonin levels were analysed in brain areas such as the whole brain, hippocampus and cerebral cortex using an HPLC-fluorescence detector. Euthanasia of mice was performed 1 h after treatment. Comparison between the control group and combination therapy and other standard drug groups showed a significant decrease in immobility in both antidepressant animal models. The combination of bupropion and minocycline showed greater benefits with respect to a reduction in the immobility time period and enhancement of dopamine, serotonin, and norepinephrine levels in the cerebral cortex, hippocampus and the whole brain when compared to the monotherapy treated groups.Hence, the side effects may be reduced drastically through this combination by a reduction in the bupropion/minocycline dosage.
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