8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) and monoamine oxidases (hMAO-A/B) for the therapy of neurodegenerative diseases. We identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition of hBChE (IC50 = 1.06 ± 0.31 nmol/L) and hMAO-B (IC50 = 4.46 ± 0.18 μmol/L). The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding, which was further studied by enzyme kinetics. Compound 19 acted as a free radical scavenger and biometal chelator, crossed the blood-brain barrier, was not cytotoxic, and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease. In addition, in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination. Importantly, chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice, underscoring the disease-modifying effect of QN 19.

Do boys with MAOA_LPR*2R allele present cognitive and learning impairments? / Meninos com o alelo maoa_lpr*2r apresentam prejuízos cognitivos e de aprendizagem?

ABSTRACT. Monoamine oxidase A (MAOA) polymorphisms have been associated with antisocial disorders. Less attention has been paid to the cognitive functioning of individuals with different MAOA alleles. No study has described the cognitive phenotype associated with the less frequent, low enzyme activity allele, MAOA_LPR*2R. Objective: We describe the cognitive correlates of boys having MAOA_LPR*2R allele, ascertained in a sample of school children with normal intelligence, not referred for behavioral disorders. Methods: Participants were eight boys, attending from the second to fifth grades in state-run schools. They were identified among 712 children with typical general cognitive ability, genotyped for MAOA_LPR polymorphism. Participants were assessed with general intelligence, mathematics and spelling achievement, and verbal and visuospatial working memory tests. Neuropsychological performance was compared to published standards, using 1 SD below the mean as a cutoff value for low performance. Results: Intelligence of boys with MAOA_LPR*2R allele varied from above average (N=2) to low average in the other children. Five out of eight boys with the MAOA_LPR*2R allele had low mathematics achievement, and three presented additional difficulties with spelling. Four out of eight children had low short-term and working memory performance. Discussion: This is the first study describing cognitive correlates and school performance in boys having the MAOA_LPR*2R allele. Having this allele, and therefore, probably low MAO-A activity, does not necessarily imply low intelligence or low school performance. However, learning difficulties, particularly in math, and low working memory performance were observed in boys having this allele. This suggests a role of MAOA in learning difficulties.

RESUMO. Polimorfismos da monoaminoxidase A (MAOA) são associados a transtornos antissociais. Menos atenção tem sido dada ao funcionamento cognitivo de indivíduos com diferentes alelos de MAOA. Nenhum estudo descreveu o fenótipo cognitivo associado ao alelo menos frequente, de baixa atividade enzimática, MAOA_LPR*2R. Objetivo: Descrevemos os correlatos cognitivos de meninos com o alelo MAOA_LPR*2R, identificados em uma amostra de escolares com inteligência normal, não encaminhados por transtornos de comportamento. Métodos: Oito meninos com o alelo MAOA_LPR*2R foram identificados entre 712 crianças genotipadas, com inteligência típica, que cursavam do 2º ao 5º ano em escolas públicas. Foram avaliados: inteligência, desempenho em matemática e ortografia, memória de trabalho verbal e visuoespacial. O desempenho foi comparado a normas publicadas, utilizando-se 1 desvio padrão (DP) abaixo da média como ponto de corte para desempenho rebaixado. Resultados: A inteligência dos meninos com alelo MAOA_LPR*2R variou de acima da média (N=2) a médio-inferior nas demais crianças. Cinco dos oito meninos com alelo MAOA_LPR*2R apresentaram desempenho rebaixado em matemática e três apresentaram dificuldades adicionais em ortografia. Quatro dos oito meninos apresentaram baixo desempenho de memória de curto prazo e de trabalho. Discussão: Este é o primeiro estudo a descrever os correlatos cognitivos e o desempenho escolar em meninos com alelo MAOA_LPR*2R. Ter esse alelo não significa necessariamente baixa inteligência ou baixo desempenho escolar. No entanto, dificuldades de aprendizagem, principalmente em matemática, e desempenho rebaixado da memória de trabalho foram observados em mais da metade dos meninos com esse alelo. Isso sugere um papel do MAOA nas dificuldades de aprendizagem.

Computational studies on the structural variations of MAO-A and MAO-B inhibitors - An in silico docking approach-Supplementary data

The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research

Computational studies on the structural variations of MAO-A and MAO-B inhibitors - An in silico docking approach-Supplementary data

The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research

Computational studies on the structural variations of MAO-A and MAO-B inhibitors - An in silico docking approach

The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research

Structure of Gardenia Blue Pigment and Its Inhibitory Activity on Monoamine Oxidase B / 中国实验方剂学杂志

ObjectiveTo study the chemical structure of gardenia blue pigment and its inhibitory activity against monoamine oxidase B （MAO-B）， in order to seek a potential feasible way for rational utilization and value enhancement of iridoids in Gardeniae Fructus. MethodIridoid glycosides in Gardeniae Fructus were hydrolyzed by cellulase to obtain their aglycones and reacted with amino acids. Then， the products were purified by column chromatography packed with D101 macroporous resin and preparative liquid chromatography to obtain gardenia blue pigments， and the gardenia blue pigments were identified by nuclear magnetic resonance （NMR） and mass spectrometry （MS）. Benzylamine was used as the reaction substrate of MAO-B and in vitro incubated with gardenia blue pigment monomers， high performance liquid chromatography （HPLC） was employed to determine the production of benzaldehyde for evaluating the inhibitory effect of gardenia blue pigments on MAO-B， the mobile phase was methanol （A） -50 mmol·L-1 potassium phosphate buffer （B， pH 3.2） （2∶3）， and the detection wavelength was 245 nm. ResultEight compounds of gardenia blue pigment A-H were synthesized and identified. In MAO-B inhibition test， compared with geniposide， the inhibitory activity of gardenia blue pigment D and E was significantly enhanced （P<0.05）. Compared with the 6β-hydroxygeniposide， the inhibitory activity of gardenia blue pigment G and H was significantly enhanced （P<0.05， P<0.01）. All the four gardenia blue pigments showed better MAO-B inhibitory activity than the prototype compounds. ConclusionGardenia blue pigment is a simple compound formed by one molecule of amino acid and one molecule of iridoid. Some gardenia blue pigments have better MAO-B inhibitory activity than the prototype compounds. The activity of gardenia blue pigment produced by different substrates is different， and the high-value gardenia blue pigment can be prepared based on experimental optimization， which can expand the application range of gardenia blue pigment and enrich the comprehensive utilization of iridoids from Gardeniae Fructus.

Degrading enzyme modified molecularly imprinted xerogel for selective adsorption and degradation of dopamine / 药学学报

In recent years, the overexpression dopamine (DA) due to the use of addictive drugs has caused concern and urgently needs to be addressed. The method used in our study is known as biomimetic sol-gel synthesis. We undertook the experiment to develop molecularly imprinted xerogel polymers (MIXPs) through template molecules dopamine polymerized with polyethyleneimine (PEI), then self-assembled and crosslinked with tetramethoxysilane (TMOS) in the form of non-covalent hydrogen bonds by using biomimetic sol-gel process, and then eluted template DA will leave a blotting site. Monoamine oxidase immobilized MIXPs (MAO-MIXPs) was obtained by coating monoamine oxidase onto MIXPs. The synthesis optimization of MAO-MIXPs was finally set as the ratio of DA template, PEI and MAO coating (DA 40 mg, PEI 0.6 mL, MAO 2.5 mg·g-1) to achieve highly selective adsorption toward DA in artificial cerebrospinal fluid based on the adsorption performance and degradation performance. The micromorphologies and physical-chemical properties of MAO-MIXPs were characterized by scanning electron microscopy, differential scanning calorimeter and Fourier transform infrared spectroscopy, and then amount of adsorption was calculated with adsorption equation. Simultaneously, the Brunner-Emmet-Teller (BET) and Langmuir model were simulated. It was found that the adsorption behavior tended to be monolayer adsorption. This new molecularly imprinted polymer demonstrated potential dopamine expression regulation for highly selective recognition, adsorption and degradation of dopamine.

Current state of monoamine oxidase A in prostate cancer / 国际外科学杂志

Recent years, the incidence of prostate cancer is increasing, and the need of novel and effective diagnosis and treatment for prostate cancer is becoming more and more urgent.Monoamine oxidase A (MAO-A) is a mitochondrial binding enzyme, which plays an important role in the deamination of some neurotransmitters. Currentlly, some novel studies have shown that MAO-A plays an important role in the occurrence, development and metastasis of prostate cancer. At present, MAO-A has become a potential therapeutic target of prostate cancer and has been widely concerned. This article make a review on the possible mechanism of MAO-A in the occurrence, development and metastasis of prostate cancer and the application of MAO-A in the diagnosis and treatment of prostate cancer.

The pharmacological interaction of compounds in ayahuasca: a systematic review

Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding about the pharmacological mechanisms that may be interacting in ayahuasca. Searches were performed using PubMed, PsycINFO, and Web of Science databases and 16 papers were selected. As hypothesized, the primary narrative in existing research revolved around prevention of deamination of N,N-dimethyltryptamine (N,N-DMT, also referred to as DMT) by monoamine oxidase inhibitors (MAOIs) in ayahuasca. Two of the constituents, DMT and harmine, have been studied more than the secondary harmala alkaloids. At present, it is unclear whether the pharmacological interactions in ayahuasca act synergistically or additively to produce psychoactive drug effects. The included studies suggest that our current understanding of the preparation's synergistic mechanisms is limited and that more complex processes may be involved; there is not yet enough data to determine any potential synergistic interaction between the known compounds in ayahuasca. Our pharmacological understanding of its compounds must be increased to avoid the potential risks of ayahuasca use.

8-Propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one: A new coumarin with monoamine oxidase B inhibitory activity and possible anti-parkinsonian effects

Parkinson's disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson's disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.

Anti-Parkinson mechanism of Foshou Powder based on factorial design / 中草药

Objective: To explore the effects and potential mechanism of Foshou Powder on Parkinson’s disease. Methods: Reserpine was injected in KM mice to establish Parkinson’s disease model, and hypothermia and akinesia were measured to evaluate the effects of volatile oil of Angelica sinensis, Ligusticum chuanxiong and combination. The human monoamine oxidase (hMAO) activity and inhibition mode were measured by fluorescence spectrophotometry in vitro with kynuramine as the common substrate of human monoamine oxidase A (hMAO-A) and human monoamine oxidase B (hMAO-B). On this basis, the 2 × 4 factorial design was applied to research the interaction between Angelica sinensis volatile oil and Ligusticum chuanxiong volatile oil. Results: The antagonistic experiments of reserpine showed that the application of Angelica sinensis volatile oil and Ligusticum chuanxiong volatile oil significantly improved hypothermia and akinesia. Enzyme activity test revealed that volatile oil of Angelica sinensis and Ligusticum chuanxiong had competitive inhibitory effects on hMAO-A and hMAO-B, and the combination of the two substances had significant synergistic effect on the activity of both hMAO. Conclusion: Angelica sinensis and Ligusticum chuanxiong in Foshou Powder have significant synergistic effects in the prevention and treatment of Parkinson’s disease, which may be related to the inhibition of MAO activity.

Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Tratamiento de la enfermedad de Parkinson temprana / Treatment of early Parkinson's disease

RESUMEN La enfermedad de Parkinson (EP) es principalmente una enfermedad de pacientes ancianos. Es un trastorno multifacético que comprende síntomas motores y no motores en todas las etapas de la enfermedad. Esta revisión busca integrar los datos de las opciones de tratamiento más recientes con los datos de las terapias establecidas, a fin de proporcionar una referencia actualizada basada en la evidencia para los médicos que tratan la EP temprana, con medicamentos que puedan usarse como alternativa a la levodopa. El enfoque de los médicos para el tratamiento de la enfermedad de Parkinson (EP) temprana debe tener en cuenta numerosos aspectos, entre ellos, cómo informar al paciente sobre el diagnóstico y la decisión crítica de qué terapia adoptar y cuándo iniciarla. El tratamiento del trastorno motor asociado con la EP temprana debe considerar varios factores cruciales, como la edad de inicio, las comorbilidades y los requisitos funcionales del paciente, y no se puede resumir en una fórmula simple. En pacientes más jóvenes (es decir, antes de la edad de 70 años) y en aquellos sin altos requisitos funcionales, el tratamiento generalmente se inicia con agonistas de dopamina y / o inhibidores de la enzima monoaminooxidasa-B (MAO- B I). En pacientes más jóvenes, la levodopa se debe agregar a los agonistas de la dopamina y / o MAO-B I, según lo requiera la progresión de la enfermedad, mientras que en los pacientes mayores, cuando la respuesta a la levodopa sola no es satisfactoria, los agonistas de la dopamina o los inhibidores de la catecol-O- metiltransferasa pueden posteriormente ser agregados.

SUMMARY Parkinson's disease (PD) is primarily a disease of elderly patients. Is a multifaceted disorder comprised of both motor and non-motor symptoms at all stages of the disease. This review seeks to integrate data from the newest treatment options with data from established therapies, so as to provide an up-to- date evidence-based reference for clinicians treating early PD, with medications that can be used as an alternative to levodopa. The clinicians' approach to the treatment of early Parkinson's disease (PD) should take into account numerous aspects, including how to inform a patient upon diagnosis and the critical decision of what therapy to adopt and when to start it. The treatment of the motor disorder associated with early PD needs to consider several crucial factors, such as age at onset, comorbidities, and the patient's functional requirements, and cannot be summarized in a simple formula. In younger patients (i.e., before the age of 70) and in those without high functional requirements, treatment is usually initiated with dopamine agonists and/or monoamine oxidase-B enzyme inhibitors (MAO-B I). In younger patients, levodopa should be added to dopamine agonists and/or MAO-B I, as required by disease progression, whereas in older patients, when response to levodopa alone is not satisfactory, dopamine agonists or catechol-O- methyltransferase inhibitors may subsequently be added.

Effect of monoamine oxidase B A644G variant on nicotine dependence and/or schizophrenia risk

Abstract Objectives Schizophrenia (Sch) is a severe and chronic mental illness. Smoking prevalence is higher in patients with Sch than general population. We aimed to investigate the effects of MAOB gene A644G variant on nicotine dependence (ND) and Sch+ND risk in Turkish population and to evaluate by bioinformatic analysis. Methods Present study included 161 individuals with ND, 223 patients with Sch+ND, and 96 non-smoker controls. MAOB A644G variant was analyzed using PCR-RFLP method. As the MAOB gene is located on the X chromosome, each gender was analysed separately. Results The total distributions of AA, AG and GG genotypes of MAOB gene A644G were 44.7%, 22.4% and 32.9% in the ND group, 45.3%, 25.1% and 29.6% in the Sch+ND group and, 44.8, 22.9% and 32.3% in non-smoker controls. No significant differences were observed between groups for the MAOB A644G genotype and allele frequencies when female group compared to male group (p > 0.05). Examination of disease associations of SNPs from each miRNA gene region in GWAS databases yielded results for aging, bipolar disorder, autoimmune, and neurological diseases. Discussion Our results indicate that the MAOB gene A644G variant is not associated with ND and/or Sch susceptibility in the Turkish population.

Postpartum depression: association with genetic polymorphisms of noradrenaline metabolic enzymes and the risk factors / 南方医科大学学报

OBJECTIVE@#To investigate the association of genetic polymorphisms of norepinephrine metabolizing enzymes with postpartum depression and analyze the risk factors for postpartum depression in women following cesarean section.@*METHODS@#A total of 591 Chinese woman of Han Nationality undergoing caesarean section were enrolled in this study. The diagnosis of postpartum depression was established for an Edinburgh Postnatal Depression Scale (EPDS) score ≥9. For all the women without antepartum depression, the genotypes of catechol-O-methyltransferase (COMT; at 5 sites including rs2020917 and rs737865) and monoamine oxidase A (rs6323) were determined using Sequenom Mass Array single nucleotide polymorphism (SNP) analysis. We analyzed the contribution of the genetic factors (SNPs, linkage disequilibrium and haplotype) to postpartum depression and performed logistic regression analysis to identify all the potential risk factors for postpartum depression and define the interactions between the genetic and environmental factors.@*RESULTS@#The incidence of postpartum depression was 18.1% in this cohort. Univariate analysis suggested that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype) were significantly correlated with the occurrence of postpartum depression ( < 0.05). Logistic regression analysis showed that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype), severe stress during pregnancy, and domestic violence were the risk factors for postpartum depression ( < 0.05); no obvious interaction was found between the genetic polymorphisms and the environmental factors in the occurrence of postpartum depression.@*CONCLUSIONS@#The rs2020917TT and rs737865GG genotypes of COMT, stress in pregnancy, and domestic violence are the risk factors for postpartum depression.

Research progress of satlnamide in treatment of Parkinson' s diseases / 中国药理学通报

Parkinson's disease (PD) is the second most common chronic progressive neurodegenerative disorder in the elderly after Alzheimer' 8 disease. Over the decadcs, levodopa has been considered the main therapy against PD. However, long term use of levodopa is often accompanicd by adverse reactions, including nausea, insomnia, dyskinesia, and "wetring-off" and " on-o/T" phenomena, ranging in severity from mild and non-disabling to incapacitating. On March 21 2017, US Food and Drug Administration ( FDA ) approved safinamide us an adjunctive treatment to levodopa in patients vilh PD experiencing " off" episodes. As a new drug for the treatment of PD, safinamide has the advantage of high selectivity and safely. This paper reviews the mechanisms and some clinical trials of safinamide.

Mechanism of essential oil of Ligusticum chuanxiong to prevent and treat vascular cognitive impairment induced by lipopolysaccharide in mice / 中草药

Objective: To explore the effect of volatile oil of Ligusticum chuanxiong on vascular cognitive impairment (VCI) induced by lipopolysaccharide (LPS) and its related mechanism. Methods Male C57BL/C mice were randomly divided into sham-operated group, model group, memantine (10 mg/kg) group, and volatile oil of L. chuanxiong (30, 15, and 7.5 mg/kg) groups, drugs were given by ig administration once a day for 14 d. On day 8, LPS was injected into the lateral ventricle in mice. On day 11 and day 12, the cognitive ability were checked by the Y maze and step down test. On day 15 the mice were decapitated and the brain tissue was taken to determine the levels of monoamine oxidase (MAO), acetylcholinesterase (AchE), and acetylcholine (Ach); At the same time, the effect of the drug on superoxide dismutase (SOD) in mitochondria of brain in SD rats and the activity of Ec AchE, and BV-2 cells of microgliomas injured by LPS were also investigated in vitro. Results:LPS significantly increased the levels of MAO and AchE in the brain in mice, while decreased the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE). The volatile oil of L. chuanxiong 30 or 15 mg/kg decreased the level of MAO and AchE in the brain of LPS mice. The volatile oil of L. Chuanxiong could significantly increase the times of spontaneous alternation reaction in Y maze in VCI mice, and the middle dose could significantly decrease the latency of VCI mice in step down test. In vitro, the volatile oil of L. chuanxiong 1 mg/mL had a weak inhibitory effect on AchE of electric eel. The volatile oil of L. chuanxiong 0.5 μg/mL could significantly increase the activity of SOD in brain mitochondria of rats, and decrease the levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) increased significantly in BV-2 cells induced by LPS. Conclusion: The volatile oil of L. chuanxiong can significantly improve the cognitive ability of VCI induced by LPS in mice, and its mechanism may be related to inhibit the inflammatory response in the brain and alleviate the injury of neurons.

Neuromodulatory effects of ethyl acetate fraction of Zingiber officinale Roscoe extract in rats with lead-induced oxidative stress / 中西医结合学报

OBJECTIVE@#This study investigated the ameliorative potential of Zingiber officinale Roscoe extract against lead-induced brain damage in rats.@*METHODS@#Thirty male rats were divided into 5 groups of 6 rats each. Lead-acetate toxicity was induced by intraperitoneal injection (10 mg/kg body weight (b.w.)) in Groups B-E. Group A (control) and Group B (lead-acetate) were left untreated; vitamin C (200 mg/kg b.w.) was administered to Group C; ethyl acetate fraction from Z. officinale extract (200 and 100 mg/kg b.w.) was administered to Group D and E by oral gavage once daily for 7 days. Changes in the content of some key marker enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO), epinephrine, dopamine, Na/K-ATPase, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as malonaldehyde (MDA) levels were determined in serum.@*RESULTS@#Exposure to lead acetate resulted in a significant decrease (P < 0.05) in the activities of BChE, AChE, Na/K-ATPase, SOD, CAT and GPx with a corresponding increase in the levels of MDA, xanthine oxidase, epinephrine, dopamine and MAO relative to the control group. Levels of all disrupted parameters were alleviated by co-administration of Z. officinale fraction and by the standard drug, vitamin C.@*CONCLUSION@#These results suggest that ethyl acetate fraction of Z. officinale extract attenuates lead-induced brain damage and might have therapeutic potential as a supplement that can be applied in lead poisoning.

Monoaminergic system and HPA axis dysfunctions in attention deficit hyperactivity disorder / 国际儿科学杂志

Attention deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children and adolescents.Its etiology and pathogenesis are still not clear.The disorder of monoamine oxidase function in the central nervous system that can result in abnormal catabolism of monoamine neurotransmitters,then lead to alteration of dopamine/norepinephrine levels,which is believed to be associated with ADHD behavior.Besides,dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is also involved in the pathogenesis of ADHD.In this review,the interaction between the monoaminergic system and HPA axis and its possible mechanism related with ADHD will be systematically summed up based on recent research.

Manejo perioperatorio de pacientes usuarios de antidepresivos / Perioperative management of patients using antidepressants

El uso de antidepresivos en el perioperatorio es muy frecuente, y la práctica clínica indica que los pacientes usuarios de antidepresivos que son sometidos a cirugía tienen un riesgo perioperatorio aumentado. No existen en la actualidad guías clínicas basadas en la evidencia que orienten el manejo de este tipo de pacientes, por lo que las recomendaciones se basan en las escasas revisiones sistemáticas y metaanálisis disponibles, reportes de casos y opinión de expertos, que en muchos casos resultan controversiales. La decisión de mantener o suspender la medicación antidepresiva implica considerar los riesgos tanto desde el punto de vista fisiológico (características generales del paciente, riesgos asociados al antidepresivo utilizado, la cirugía propiamente como tal, la interacción con fármacos frecuentemente utilizados en el perioperatorio, entre otros) como desde el punto de vista psiquiátrico (riesgo de síndrome de retirada, recaída de la enfermedad psiquiátrica, intentos suicidas), por lo que la decisión debe ser tomada idealmente de forma multidisciplinaria entre cirujanos, anestesiólogos y psiquiatras, con la idea de confeccionar un plan quirúrgico, anestésico y de manejo perioperatorio seguro para el paciente.

Antidepressant use in the perioperative is a common practice, and clinical evidence shows that surgical patients using antidepressants have an increased perioperative risk. There are not evidence-based guidelines for the perioperative management of these patients, and recommendations are based on few systematic reviews and meta-analysis, case reports and expert opinion, which in many cases are controversial. The decision to continue or discontinue the medication involves considering general patient characteristics, risks associated with the antidepressant used, type of surgery, interaction with drugs commonly used in the perioperative, risk of withdrawal symptoms, relapse of psychiatric disease and suicide risk, so decision should be made between surgeons, anesthesiologists and psychiatrists, in order to design a safe management plan for the patient who undergo surgery.