Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced ...Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.展开更多
Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to ...Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to conduct a systematic review with meta-analysis to investigate the effects that Rasagiline has on motor and non-motor symptoms in individuals with PD. Introduction: Rasagiline is a second-generation monoamine oxidase-B (MAO-B) inhibitor used both as monotherapy and adjunctive therapy for Parkinsons Disease (PD). Methods: A systematic literature search and meta-analysis were performed with randomized control trials that investigated the effects of Rasagiline on motor and non-motor symptoms in individuals with PD. The systematic search was conducted in PubMed, Cochrane, and EBSCO databases. Methodological quality was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Results: Fourteen studies were included in our review. There were trivial to small and statistically significant improvements in motor symptoms for individuals with PD treated with Rasagiline compared to placebo. Non-motor symptoms showed no significant improvement with Rasagiline compared to placebo in five of six meta-analyses. Results were based on very low to moderate certainty of evidence. Conclusion: 1 mg/day Rasagiline significantly improved Parkinsonian motor symptoms in individuals with PD compared with placebo. For all outcomes, the 1 mg/day Rasagiline group was favored over the placebo group.展开更多
Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy o...Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy of a monoamine oxidase type B inhibitor (MAOBI) with levodopa or a catechol-O-methyl transferase inhibitor (COMTI) with levodopa provides benefits to PD patients. Direct comparison of efficacy and side effect profiles is complex. The aim of this study is to investigate the different AE profiles of MAOBI and COMTI combination therapies. Data used to analyze the AEs of different PD medications were retrieved from “The Boston University Medical Center’s Parkinson’s Disease and Movement Disorder Database”. Ten categories of AEs were compared between patients receiving MAOBI and COMTI combination treatment. In total, 87 subjects were included in the analysis. Out of ten AEs, the presence of dementia was signifi- cantly different between the MAOBI and COMTI groups with an OR of 6.9 (COMTI vs MAOBI, 95% CI 1.3 - 37.0). Motor fluctuations were also found to be differently distributed in the two medication groups with an OR of 3.1 (COMTI vs MAOBI, 95% CI 1.0 - 9.8). In this retrospective database analysis of patients treated with combination treatment for PD, combination therapy of a COMTI with levodopa was more likely to be associated with dementia and motor fluctuations than a MAOBI with levodopa.展开更多
Ayurveda is a renowned traditional medicine practiced in India from ancient times and Clitoria ternatea is one such prospective medicinal herb incorporated as an essential constituent in a brain tonic called as medhya...Ayurveda is a renowned traditional medicine practiced in India from ancient times and Clitoria ternatea is one such prospective medicinal herb incorporated as an essential constituent in a brain tonic called as medhya rasayan for treating neurological disorders.This work emphasises the significance of the plant as a brain drug there by upholding Indian medicine.The phytochemicals from the root extract were extricated using gas chromatography–mass spectrometry assay and molecular docking against the protein Monoamine oxidase was performed with four potential compounds along with four reference compounds of the plant.This persuades the prospect of C.ternatea as a remedy for neurodegenerative diseases and depression.The in silico assay enumerates that a major compound(Z)-9,17-octadecadienal obtained from the chromatogram with a elevated retention time of 32.99 furnished a minimum binding affinity energy value of-6.5 kcal/mol against monoamine oxidase(MAO-A).The interactions with the amino acid residues ALA 68,TYR 60 and TYR 69 were analogous to the reference compound kaempferol-3-monoglucoside with a least score of-13.90/-12.95 kcal/mol against the isoforms(MAO)A and B.This study fortifies the phytocompounds of C.ternatea as MAO-inhibitors and to acquire a pharmaceutical approach in rejuvenating Ayurvedic medicine.展开更多
In the theory of traditional Chinese medicine, aging is mainly thought renal deficiency caused renal failure, mainly involving decline of kidney-Yang and deficiency of kidney-essence. Huanshaodan, a Chinese traditiona...In the theory of traditional Chinese medicine, aging is mainly thought renal deficiency caused renal failure, mainly involving decline of kidney-Yang and deficiency of kidney-essence. Huanshaodan, a Chinese traditional preparation for kidney-replenishing essence, was used to be the preparation for reinforcing renal deficiency and preventing aging for aged people. OBJECTIVE： To observe the effects of Huanshaodan on swimming durance and the abilities of catalase （CAT） in serum and monoamine oxidase-B （MAO-B） in brain tissue as well as in vitro anti-oxidative ability of aging mouse. DESIGN： A controlled animal experiment. SETTING： College of Basic Medicine, Hunan University of Traditional Chinese Medicine. MATERIALS： Fifty-four healthy NIH mice, aged 18 months old, of either gender, weighing （48.9±5.4） g, and one SD male rat, aged 16 months old, weighing 51.7 g, were provided by Animal Experimental Center, Hunan University of Traditional Chinese Medicine. Thirty NIH mice were randomly chosen for swimming test, and divided into experimental group and control group, with 15 in each; The other 24 NIH mice were used for enzyme activity assay, and also divided into experimental group and control group, with 12 in each. SD rat was used for in vitro anti-oxidative ability test, Huanshaodan water decoction was composed of Cheqianzi, Wuweizi, Huaishan, Danggui, Huangbai, Shudi, Baizhi, Niuxi, Baishen, Tusizi, Buguzhi, Roucongrong and Heshouwu 13 Chinese herbs. METHODS： This study was carried out in the Second Laboratory, Department of Biochemistry, Hunan University of Traditional Chinese Medicine in June 2006. Swimming and enzyme activity assay： Mice in the two experimental groups were intragastrically administrated with l0 μL/g Huanshaodan water decoction. Mice in the two control groups were intragastrically administrated with the same amount of normal saline. All the mice were intragastrically administrated for 5 days, and they were free to access to medicine in the other 2 days in a week. Each mouse was administrated for 8 weeks. MAIN OUTCOME MEASURES： ① Forty days after administration, mice in the experimental group and control group for swimming test were loaded at tails and allowed to swim in the water-tank. Swimming durance was recorded. ② Following the method of Chen Qi, the activities of CAT in serum and MAO-B in brain tissue as well as the inhibitory rate of each medicine on malonaldehyde （MDA） content in the in vitro rat hepatic tissue were determined; Meanwhile, the inhibitory rate of different doses of Tusizi liquid to MDA content in the rat hepatic tissue in vitro was also assayed. RESULTS： Fifty-four NIH mice and one SD rat were recruited in this experiment. Three mice died in the swimming test, and all the other animals were involved in the final analysis. ① Swimming durance of mice in the experimental group was significantly longer than that in the control group （ t =7.502, P 〈 0.01 ） . The activity of CAT in serum of mice in the experimental group was significantly higher than that in the control group （ t =13.307, P 〈 0.01 ） . ② The activity of MAO-B in brain tissue of mice in the experimental group was significantly lower than that in the control group （t =l3.27, P 〈 0.01 ） . ③The inhibitory rate of Cheqianzi, Wuweizi, Huaishan, Danggui, Huangbai, Shudi, Baizhi, Niuxi, Baishen, Tusizi, Buguzhi, Roucongrong and Heshouwu 13 Chinese herbs of Huanshaodan to MDA in the rat hepatic tissue in vitro was - 62.9, - 95.1, - 34.9, - 65.1, - 99.1, - 87.2, - 94.1, - 20.0, - 67.0, - 83.7, - 91.0, - 98.4, - 93.0, respectively. ④ The inhibitory rate of low to high dose of Tusizi liquid to MDA content in the rat hepatic tissue in vitro was - 3.41, - 18.1, - 26.6, - 83.7, respectively. CONCLUSION： Huanshaodan enhances swimming endurance, anti-oxygen free radical and anti-oxidativeabilities, and thus, it can delay aging.展开更多
Rasagiline,a monoamine oxidase-B inhibitor,and bis（propyl）-cognitin（B3C）,a novel dimer are reported to be neuroprotective.Herein,the synergistical neuroprotection produced by rasagiline and B3 C was investigated i...Rasagiline,a monoamine oxidase-B inhibitor,and bis（propyl）-cognitin（B3C）,a novel dimer are reported to be neuroprotective.Herein,the synergistical neuroprotection produced by rasagiline and B3 C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced mice of Parkinsonism.By using neurobehavioural tests,high-performance liquid chromatography and western blot assay,we showed that B3 C at 0.3 mg/kg,rasagiline at 0.02 mg/kg,as well as co-treatment with B3 C and rasagiline prevented MPTP-induced behavioural abnormities,increased the concentrations of dopamine and its metabolites in the striatum,and up-regulated the expression of tyrosine hydroxylase in the substantia nigra.However,the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3 C or rasagiline alone.Collectively,we have demonstrated that B3 C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.展开更多
文摘Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.
文摘Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to conduct a systematic review with meta-analysis to investigate the effects that Rasagiline has on motor and non-motor symptoms in individuals with PD. Introduction: Rasagiline is a second-generation monoamine oxidase-B (MAO-B) inhibitor used both as monotherapy and adjunctive therapy for Parkinsons Disease (PD). Methods: A systematic literature search and meta-analysis were performed with randomized control trials that investigated the effects of Rasagiline on motor and non-motor symptoms in individuals with PD. The systematic search was conducted in PubMed, Cochrane, and EBSCO databases. Methodological quality was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Results: Fourteen studies were included in our review. There were trivial to small and statistically significant improvements in motor symptoms for individuals with PD treated with Rasagiline compared to placebo. Non-motor symptoms showed no significant improvement with Rasagiline compared to placebo in five of six meta-analyses. Results were based on very low to moderate certainty of evidence. Conclusion: 1 mg/day Rasagiline significantly improved Parkinsonian motor symptoms in individuals with PD compared with placebo. For all outcomes, the 1 mg/day Rasagiline group was favored over the placebo group.
文摘Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy of a monoamine oxidase type B inhibitor (MAOBI) with levodopa or a catechol-O-methyl transferase inhibitor (COMTI) with levodopa provides benefits to PD patients. Direct comparison of efficacy and side effect profiles is complex. The aim of this study is to investigate the different AE profiles of MAOBI and COMTI combination therapies. Data used to analyze the AEs of different PD medications were retrieved from “The Boston University Medical Center’s Parkinson’s Disease and Movement Disorder Database”. Ten categories of AEs were compared between patients receiving MAOBI and COMTI combination treatment. In total, 87 subjects were included in the analysis. Out of ten AEs, the presence of dementia was signifi- cantly different between the MAOBI and COMTI groups with an OR of 6.9 (COMTI vs MAOBI, 95% CI 1.3 - 37.0). Motor fluctuations were also found to be differently distributed in the two medication groups with an OR of 3.1 (COMTI vs MAOBI, 95% CI 1.0 - 9.8). In this retrospective database analysis of patients treated with combination treatment for PD, combination therapy of a COMTI with levodopa was more likely to be associated with dementia and motor fluctuations than a MAOBI with levodopa.
文摘Ayurveda is a renowned traditional medicine practiced in India from ancient times and Clitoria ternatea is one such prospective medicinal herb incorporated as an essential constituent in a brain tonic called as medhya rasayan for treating neurological disorders.This work emphasises the significance of the plant as a brain drug there by upholding Indian medicine.The phytochemicals from the root extract were extricated using gas chromatography–mass spectrometry assay and molecular docking against the protein Monoamine oxidase was performed with four potential compounds along with four reference compounds of the plant.This persuades the prospect of C.ternatea as a remedy for neurodegenerative diseases and depression.The in silico assay enumerates that a major compound(Z)-9,17-octadecadienal obtained from the chromatogram with a elevated retention time of 32.99 furnished a minimum binding affinity energy value of-6.5 kcal/mol against monoamine oxidase(MAO-A).The interactions with the amino acid residues ALA 68,TYR 60 and TYR 69 were analogous to the reference compound kaempferol-3-monoglucoside with a least score of-13.90/-12.95 kcal/mol against the isoforms(MAO)A and B.This study fortifies the phytocompounds of C.ternatea as MAO-inhibitors and to acquire a pharmaceutical approach in rejuvenating Ayurvedic medicine.
文摘In the theory of traditional Chinese medicine, aging is mainly thought renal deficiency caused renal failure, mainly involving decline of kidney-Yang and deficiency of kidney-essence. Huanshaodan, a Chinese traditional preparation for kidney-replenishing essence, was used to be the preparation for reinforcing renal deficiency and preventing aging for aged people. OBJECTIVE： To observe the effects of Huanshaodan on swimming durance and the abilities of catalase （CAT） in serum and monoamine oxidase-B （MAO-B） in brain tissue as well as in vitro anti-oxidative ability of aging mouse. DESIGN： A controlled animal experiment. SETTING： College of Basic Medicine, Hunan University of Traditional Chinese Medicine. MATERIALS： Fifty-four healthy NIH mice, aged 18 months old, of either gender, weighing （48.9±5.4） g, and one SD male rat, aged 16 months old, weighing 51.7 g, were provided by Animal Experimental Center, Hunan University of Traditional Chinese Medicine. Thirty NIH mice were randomly chosen for swimming test, and divided into experimental group and control group, with 15 in each; The other 24 NIH mice were used for enzyme activity assay, and also divided into experimental group and control group, with 12 in each. SD rat was used for in vitro anti-oxidative ability test, Huanshaodan water decoction was composed of Cheqianzi, Wuweizi, Huaishan, Danggui, Huangbai, Shudi, Baizhi, Niuxi, Baishen, Tusizi, Buguzhi, Roucongrong and Heshouwu 13 Chinese herbs. METHODS： This study was carried out in the Second Laboratory, Department of Biochemistry, Hunan University of Traditional Chinese Medicine in June 2006. Swimming and enzyme activity assay： Mice in the two experimental groups were intragastrically administrated with l0 μL/g Huanshaodan water decoction. Mice in the two control groups were intragastrically administrated with the same amount of normal saline. All the mice were intragastrically administrated for 5 days, and they were free to access to medicine in the other 2 days in a week. Each mouse was administrated for 8 weeks. MAIN OUTCOME MEASURES： ① Forty days after administration, mice in the experimental group and control group for swimming test were loaded at tails and allowed to swim in the water-tank. Swimming durance was recorded. ② Following the method of Chen Qi, the activities of CAT in serum and MAO-B in brain tissue as well as the inhibitory rate of each medicine on malonaldehyde （MDA） content in the in vitro rat hepatic tissue were determined; Meanwhile, the inhibitory rate of different doses of Tusizi liquid to MDA content in the rat hepatic tissue in vitro was also assayed. RESULTS： Fifty-four NIH mice and one SD rat were recruited in this experiment. Three mice died in the swimming test, and all the other animals were involved in the final analysis. ① Swimming durance of mice in the experimental group was significantly longer than that in the control group （ t =7.502, P 〈 0.01 ） . The activity of CAT in serum of mice in the experimental group was significantly higher than that in the control group （ t =13.307, P 〈 0.01 ） . ② The activity of MAO-B in brain tissue of mice in the experimental group was significantly lower than that in the control group （t =l3.27, P 〈 0.01 ） . ③The inhibitory rate of Cheqianzi, Wuweizi, Huaishan, Danggui, Huangbai, Shudi, Baizhi, Niuxi, Baishen, Tusizi, Buguzhi, Roucongrong and Heshouwu 13 Chinese herbs of Huanshaodan to MDA in the rat hepatic tissue in vitro was - 62.9, - 95.1, - 34.9, - 65.1, - 99.1, - 87.2, - 94.1, - 20.0, - 67.0, - 83.7, - 91.0, - 98.4, - 93.0, respectively. ④ The inhibitory rate of low to high dose of Tusizi liquid to MDA content in the rat hepatic tissue in vitro was - 3.41, - 18.1, - 26.6, - 83.7, respectively. CONCLUSION： Huanshaodan enhances swimming endurance, anti-oxygen free radical and anti-oxidativeabilities, and thus, it can delay aging.
基金supported by grants from the Natural Science Foundation of Guangdong Province of China,No.2015A030313317a grant from the Science and Technology Program of Guangzhou City of China,No.2014J4100097+3 种基金partially by a grant from the Science and Technology Development Fund(FDCT) of Macao Special Administrative Region,No.134/2014/A3a grant from the Research Committee of University of Macao,No.MYRG139(Y1-L4)-ICMS12-LMY and MYRG2015-00214-ICMS-QRCMgrants from the Research Grants Council of Hong Kong Special Administrative Region of China,No.561011,15101014the Hong Kong Polytechnic University of China,No.G-SB10,G-UC15 and G-YBGQ
文摘Rasagiline,a monoamine oxidase-B inhibitor,and bis（propyl）-cognitin（B3C）,a novel dimer are reported to be neuroprotective.Herein,the synergistical neuroprotection produced by rasagiline and B3 C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced mice of Parkinsonism.By using neurobehavioural tests,high-performance liquid chromatography and western blot assay,we showed that B3 C at 0.3 mg/kg,rasagiline at 0.02 mg/kg,as well as co-treatment with B3 C and rasagiline prevented MPTP-induced behavioural abnormities,increased the concentrations of dopamine and its metabolites in the striatum,and up-regulated the expression of tyrosine hydroxylase in the substantia nigra.However,the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3 C or rasagiline alone.Collectively,we have demonstrated that B3 C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.
