Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinson’s Disease: A Systematic Review and Meta-Analysis

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.

Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease

There is a substantial amount of evidence from experimental parkinsonian models to show the neuroprotective effects of monoamine oxidase-B(MAOB)inhibitors.They have been studied for their potential disease-modifying effects in Parkinson’s disease(PD)for over 20 years in various clinical trials.This review provides a summary of the clinical trials and discusses the implications of their results in the context of disease-modification in PD.Earlier clinical trials on selegiline were confounded by symptomatic effects of this drug.Later clinical trials on rasagiline using delayed-start design provide newer insights in disease-modification in PD but success in achieving the aims of this strategy remain elusive due to obstacles,some of which may be insurmountable.

Anti-free radical,anti-oxidative ability and anti-fatigue effects of Huanshaodan An experiment of aging mice

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.

Novel strategy of constructing fluorescent probe for MAO-B via cascade reaction and its application in imaging MAO-B in human astrocyte

To detect monoamine oxidase B(MAO-B), the level of which is one of the most important indicators of neurodegenerative diseases such as Parkinson's disease, a new type of cascade reaction based on the formation of coumarin was applied in this research. After the reaction with MAO-B, the protecting group of hydroxyl group in probes(DEAN-MA and DEAB-MA) was removed, and the fluorescence intensity significantly increased(l_(em) 456 nm) as the structure of coumarin was formed subsequently. The probes showed excellent sensitivity and selectivity to MAO-B. The detection limit of DEAN-MA and DEAB-MA were 0.6ng/mL and 0.2 ng/mL, respectively. We succeeded in detecting MAO-B in vitro and imaging it in human astrocyte(U87).