Occupational exposure to 1-bromopropane (1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BP-induced cognitive dysfunction. Male Wistar rats were administered with MK801 (0.1 mg/kg) prior to 1-BP intoxication (800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological, and immunological analyses. We found that the spatial learning and memory were significantly impaired in the 1-BP group, and this was associated with neurodegeneration in both the hippocampus (especially CA1 and CA3) and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex. Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.
Animals ; Brain ; drug effects ; metabolism ; pathology ; Cognitive Dysfunction ; drug therapy ; metabolism ; pathology ; Disease Models, Animal ; Dizocilpine Maleate ; pharmacology ; Excitatory Amino Acid Antagonists ; pharmacology ; Hydrocarbons, Brominated ; Inflammasomes ; drug effects ; metabolism ; Male ; Maze Learning ; drug effects ; physiology ; Microglia ; drug effects ; metabolism ; pathology ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Neurons ; drug effects ; metabolism ; pathology ; Nootropic Agents ; pharmacology ; Random Allocation ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; metabolism ; Spatial Memory ; drug effects ; physiology ; Specific Pathogen-Free Organisms

This study was to evaluate the efficacy and safety of early application of citicoline in the treatment of patients with acute stroke by meta-analysis. Randomized controlled trials published until May 2015 were electronically searched in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, WHO International Clinical Trial Registration Platform, Clinical Trial.gov, and China Biology Medicine disc. Two reviewers independently screened the articles and extracted the data based on the inclusion and exclusion criteria. The quality of included articles was evaluated by using Revman5.0, and meta-analysis was performed. The results showed that 1027 articles were obtained in initial retrieval, and finally 7 articles, involving a total of 4039 cases, were included for analysis. The meta-analysis showed that no significant differences were found in the long-term mortality (OR=0.91, 95% CI 0.07 to 1.09, P=0.30), the rate of dependency (OR=1.02, 95% CI 0.87 to 1.24, P=0.85), and the effective rate (OR=0.98, 95% CI 0.84 to 1.14, P=0.82) between citicoline group and control group. The overall rate of adverse events in citicoline group was not significantly different from that in control group (P=0.30). The quality of included articles reached moderate-low level. In conclusion, citicolne cannot reduce long-term mortality and dependence rate in the treatment of acute stroke, and the effective rate of citivoline may be not better than that of controls but with reliable safety.
Aged ; Cytidine Diphosphate Choline ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Nootropic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Stroke ; drug therapy

OBJECTIVE: To investigate the effect of combined therapy of exercise and nootropic agent on cognitive function in a focal cerebral infarction rat model. METHOD: Forty 10-week old male Sprague-Dawley rats were subjected to photothrombotic cerebral infarction of the left parietal lobe. All rats were randomly divided into 4 groups: group A was photothrombotic cerebral infarction rats without any treatment (n=10); group B was photothrombotic cerebral infarction rats with swimming exercise (n=10); group C was photothrombotic cerebral infarction rats with oral administration of acetyl-L-carnitine (n=10); group D was photothrombotic cerebral infarction rats with swimming exercise and oral administration of acetyl-L-carnitine (n=10). Cognitive function was evaluated using the Morris water maze test on the 1st day, and the 1st, 2nd, and 4th week after the induction of cerebral infarction. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in the hippocampus were measured. The neuronal cells of the hippocampus were histopathologically evaluated. RESULTS: The escape latency was shorter in groups B, C, and D than in group A. However, the differences were not statistically significant at the 1st, 2nd and 4th week. The activity of SOD was the highest in group D. The level of MDA was the lowest in group D. We observed more normal neuronal cells in groups B, C, and D. CONCLUSION: The combined therapy of exercise and nootropic agent was helpful in ameliorating oxidative stress in the focal cerebral infarction rat model. However, the effect did not translate into improvement of cognitive function.
Acetylcarnitine ; Administration, Oral ; Animals ; Cerebral Infarction ; Cognition ; Hippocampus ; Humans ; Male ; Malondialdehyde ; Maze Learning ; Neurons ; Nootropic Agents ; Oxidative Stress ; Parietal Lobe ; Piracetam ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; Swimming ; United Nations

Conditioned fear and its abnormal extinction are involved in the psychopathology of anxiety disorders, such as posttraumatic stress disorder (PTSD). Cognitive enhancing agents have been demonstrated to alter fear extinction in many animal research literatures. The present review has examined the pharmacological role of gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid as well as compounds able to alter the epigenetic and neurotrophic mechanism in fear extinction, highlighting great hope for the future treatment of anxiety disorders with new agents based on the fear extinction.
Animals ; Anxiety Disorders ; drug therapy ; psychology ; Cannabinoids ; pharmacology ; therapeutic use ; Conditioning, Psychological ; drug effects ; Extinction, Psychological ; drug effects ; Fear ; drug effects ; psychology ; Humans ; Nootropic Agents ; pharmacology ; Stress Disorders, Post-Traumatic ; drug therapy ; psychology ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

Animals ; Dementia, Vascular ; drug therapy ; physiopathology ; Hippocampus ; metabolism ; physiopathology ; Learning ; drug effects ; Male ; Memory ; drug effects ; Nootropic Agents ; pharmacology ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Pyrrolidinones ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe clinical therapeutic effect of acupuncture combined with Yizhi Jiannao Granules for treatment of Alzheimer's disease and its effects on intelligence, daily life and social activity ability.

METHODSEighty-four cases were randomly divided into 3 groups, 28 cases in each group. The combined acupuncture and medication group was treated with acupuncture at Baihui (GV 20), Sishencong (EX-HN 1), Dazhui (GV 14), Guanyuan (CV 4), etc. and oral administration of Yizhi Jiannao Granules; the Chinese herb group was treated with Yizhi Jiannao Granules, and the western medicine group with oral administration of Aricept. The scores for the Mini-Mental State Examination (MMSE), Ability of Daily Life (ADL) and the therapeutic effects were assessed and compared before treatment and after treatment for 12 weeks among the groups.

RESULTSAfter treatment, the scores for MMSE and ADL were improved in the combined acupuncture and medication group, the Chinese herb group and the western medicine group, which were better in the combined acupuncture and medication group (P < 0.05). The total effective rate of 85.7% in the combined acupuncture and medication group was better than 71.4% in the Chinese herb group and 67.9% in the western medicine group.

CONCLUSIONAcupuncture combined with Yizhi Jiannao Granules has a significant therapeutic effect on Alzheimer's disease, which is better than that of Yizhi Jiannao Granules or Aricept.

Acupuncture Points ; Acupuncture Therapy ; methods ; Administration, Oral ; Aged ; Alzheimer Disease ; psychology ; therapy ; Combined Modality Therapy ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Humans ; Indans ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Nootropic Agents ; administration & dosage ; therapeutic use ; Piperidines ; administration & dosage ; therapeutic use ; Quality of Life ; Treatment Outcome

This paper reviews history of new drug development in Korea as well as researchs on development of new psychotherapeutic drug from traditional medicines or natural products in Korea. Korea has a long history of traditional medicine and accumulated knowledge of natural resources. However, only a few new drug have been developed from those natural products. Now many researchers in Korea are devoting themselves to test the possibility of natural products as antipsychotic drugs, antidepressants, anxiolytic drugs and cognitive enhancers. However, only a few graduates from traditional medical schools in Korea are engaging in research on developing new drug from natural products and they are not familiar to research methods of western medicine and pharmacology. For research and development of new drug from natural products or traditional medicines, many researchers should be trained for methodology of basic medicine, pharmacology, pharmacognosy, and oriential pharmacy. Government and pharmaceutical companies need to provide more investment for R & D for new drug from natural products including establishment of data base for component of traditional medicines and natural products, system development integrating information technology, bio-technology and nanotechnology, and international collaboration with advanced countries which have common interest in new drug development from natural products.
Antidepressive Agents ; Antipsychotic Agents ; Biological Products ; Natural Resources ; Cooperative Behavior ; Investments ; Korea ; Medicine, Korean Traditional ; Medicine, Traditional ; Nanotechnology ; Nootropic Agents ; Pharmacognosy ; Pharmacology ; Pharmacy ; Schools, Medical

OBJECTIVETo study the efficacy and safety of Reinhartdt and sea cucumber capsule (RSC) combined with donepezil in treating Alzheimer's disease (AD), and its effect on thyroid function axis.

METHODSSixty-eight patients were randomly assigned to the RSC group, the Donepezil group and the combined treatment group, who were treated for 3 and 6 months with RSC, Donepezil and RSC combined with Donepezil, respectively. The curative effect was evaluated by scoring according to Mini-Mental State Examination (MMSE), ADAS-Cog and ADL chart, and the level of thyroid hormones, including TSH, FT3, FT4, TT3 and TT4, were measured with radioimmunoassay before treatment, 3 and 6 months after treatment respectively.

RESULTSAs compared with the baseline, MMSE score increased, ADAS-Cog score and ADL score decreased significantly in all the three groups after 3 months and 6 months of treatment (P < 0.05 and P < 0.01), but the improvement in the combined treatment group was more significant than that in the other two groups (P < 0.01). After 6 months of treatment, the levels of FT3 and FT4 in the combined treatment group were significantly changed (P < 0.01), but no significant change in all the thyroid hormones was found in the other two groups. No obvious adverse reaction occurred in all the three groups.

CONCLUSIONRSC combined with Donepezil in treating AD is effective and safe with no evident adverse reaction, better than single drug treatment, which may be through influencing the metabolism of thyroid hormones to improve the cognition function of AD patients.

Aged ; Aged, 80 and over ; Alzheimer Disease ; drug therapy ; Animals ; Capsules ; Drug Therapy, Combination ; Female ; Humans ; Indans ; therapeutic use ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Nootropic Agents ; therapeutic use ; Piperidines ; therapeutic use ; Radioimmunoassay ; Sea Cucumbers ; chemistry ; Thyroid Hormones ; blood

OBJECTIVETo study the efficacy and safety of the combined treatment with compound Reinhartdt and Sea Cumber Capsule (RSC, a Chinese medicinal preparation consisted mainly of Reinhartdt and Sea Cumber) and Donepezil for vascular dementia (VD), and its effect on thyroid function axis.

METHODSSixty-three patients with VD were treated respectively with RSC, Donepezil and the combined treatment. MMSE, ADAS-Cog and ADL scales were used to evaluate the condition of patients before treatment as well as at 3 months and 6 months after treatment. Meanwhile, levels of thyroid hormones, including (TSH, FT3, FT4, TT3, TT4) were measured with radioimmunoassay.

RESULTSAs compared with the baseline, MMSE score increased, ADAS-Cog score and ADL score decreased significantly in all the three groups after 3 months and 6 months of treatment (P <0.05, P<0.01), the improvement in the Donepezil group was more significant than that in the RSC group after 6 months of treatment (P < 0.05), but the combined treatment group showed the best efficacy (P < 0.01). After 3 months of treament, the levels of FT3 and FT4 in the combined treatment group increased, but showed no statistical significance (P >0.05). However, significant changes were found at 6 months after combined treatment (P < 0.01). No significant changes were seen at all in levels of TSH, TT3 and TT4 (P > 0.05). FT3, FT4 increased without statistical significance after 6 months Donepezil treatment, TSH, TT3 and TT4 also showed no significant difference in the Donepezil group and no other significant changes of thyroid hormones was seen in patients treated with RSC (P > 0.05). No obvious adverse reaction occurred in any of the three groups.

CONCLUSIONCombined treatment of RSC and Donepezil was effective and safe on VD patient, with the efficacy much better than either of them alone. No significant adverse reaction was observed. The regulation on thyroid hormones may one of the mechanisms of the combined treatment in improving cognitive function.

Aged ; Aged, 80 and over ; Capsules ; Dementia, Vascular ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Indans ; therapeutic use ; Male ; Materia Medica ; therapeutic use ; Medicine, Chinese Traditional ; Middle Aged ; Nootropic Agents ; therapeutic use ; Piperidines ; therapeutic use ; Treatment Outcome

OBJECTIVETo observe the therapeutic effect of Shenyin Oral Liquid (SOL) in relieving mild cognitive impairment (MCI) and decreasing the Alzheimer's disease (AD) transformation rate.

METHODSOne hundred and seventeen MCI patients were randomly assigned to the Chinese medicine group (42 cases), the vitamin E group (38 cases) and the placebo group (37 cases). The treatment course was 12 months and a 6-month follow-up was conducted after ending the treatment course.

RESULTSAfter treatment, the scores of clock drawing test (CDT), nonsensical figure recognition and mini-mental state examination (MMSE) raised significantly in the Chinese medicine group (P < 0.05 or P < 0.01), the activity of acetylcholine esterase in erythrocytic membrane was lower in the Chinese medicine group than that in the placebo group and the Vitamin E group (P < 0.05 or P < 0.01). Six months after the treatment, there were 2 and 5 cases in the placebo group and the vitamin E group which were diagnosed as AD, respectively, and none in the Chinese medicine group.

CONCLUSIONSOL has an effect similar to cholinesterase inhibitor, it could improve cognitive function in MCI patients and reduce the AD transformation rate in them.

Aged ; Alzheimer Disease ; prevention & control ; Cognition Disorders ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Memory ; drug effects ; Mental Status Schedule ; Middle Aged ; Nootropic Agents ; therapeutic use ; Phytotherapy ; Treatment Outcome