MAO Activity Research Articles

Prospected epigenetic moderators from natural sources and drug of class NSAIDS as effective treatment options to Prostate cancer

Objective: To evaluate the effect of sinapic acid against Aluminium chloride-induced dementia of Alzheimer's disease (AD) type in rat. Methods: The study was designed to induce dementia by chronic exposure of aluminium chloride at a dose of 175 mg/kg, p.o. for a period of 25 days in rats and then divided into different groups, i.e. Treatment group, negative control and two groups of sinapic acid, (at a dose of 20 and 40mg/kg, p.o.), where these groups treated and observed till the 35th day of experimental trial. The behavioural, neuronal and biochemical parameters were determined during or end of experiment. Histological changes in the brain were also observed. Results: Aluminium chloride at a dose of 175 mg/kg, o.p. had significantly induced the dementia and sinapic acid, at a dose of 40 mg/kg, p.o., possessed therapeutic effect against Aluminium chloride induced-dementia of AD type in rats. Conclusions: Sinapic acid is a class of compound wide spread in plant kingdom and could be a better source of neutraceuticals in brain disorders. The compound showed an in vivo MAO-A and MAO-B inhibiting activity and their role in Alzheimer's disease type of dementia was unexplored. The article also provides information on acute toxicity of sinapic acid with no toxicological sign on brain with chronic dose of AlCl3.

Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner.

Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC) and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR) or with normal diet (CTL) for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA) was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological disorders. Our findings show that nutritional iron deficiency produces these molecular alterations in a region-specific manner and provide new insight into the variety of molecular pathways that can lead to distinct neurological symptoms upon iron deficiency. Thus, adequate iron supplementation is essential for brain health and prevention of neurological diseases.

Determination of antidepressant activity of <i>Cyperus rotundus</i> L extract in rats

Purpose: To investigate the antidepressant effect of Cyperus rotundus L. extract (CRLE) in rats.Methods: A rat model of depression was prepared for behavioral tests including tail suspension test or forced swimming test. Wistar rats were randomly divided into six groups (n = 10): normal group (0.9 % NaCl), model group (0.9 % NaCl), positive drug group (fluoxetine 30 mg/kg) as well as CRLE groups, namely, 200, 400 and 800 mg/kg doses. All drugs were orally administered at 14: 00 - 15: 00 h for 1, 7 and 14 days, respectively. Tail suspension and forced swimming tests were conducted 1 h after the last treatment. Monoamine oxidize A (MAO) assay was commenced in rats after 14-day administration. Except for the rats in normal group, other group participated in the behavioral tests.Results: The effect of 800 mg/kg CRLE was more potent than the positive drug fluoxetine. CRLE (≥ 200 mg/kg) treatment for 14 days significantly inhibited brain MAO activity in rats (p < 0.01) in a dosedependent manner. Oral administration of 800 mg/kg CRLE produced MAO B inhibitory activity in rat brain (p < 0.01). Fluoxetine inhibited both brain MAO A and B activities in rats (p < 0.01).Conclusion: The results suggest that CRLE produces significant antidepressant effect in rats, and therefore, may be useful for the treatment of depressed patients, but further studies are required to ascertain this.Keywords: Cyperus rotundus, Antidepressant, Tail suspension test, Forced swimming test, Monoamine oxidase, Fluoxetine

MPTP Mouse Model of Preclinical and Clinical Parkinson's Disease as an Instrument for Translational Medicine.

Parkinson's disease (PD) is characterized by the appearance of motor symptoms many years after the onset of neurodegeneration, which explains low efficiency of therapy. Therefore, one of the priorities in neurology is to develop an early diagnosis and preventive treatment of PD, based on knowledge of molecular mechanisms of neurodegeneration and neuroplasticity in the nigrostriatal system. However, due to inability to diagnose PD at preclinical stage, research and development must be performed in animal models by comparing the nigrostriatal system in the models of asymptomatic and early symptomatic stages of PD. In this study, we showed that despite the progressive loss of neurons in the substantia nigra at the presymptomatic and symptomatic stage, almost no change was observed in the main functional characteristics of this brain region, including dopamine (DA) uptake and release, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) expression, and activity of MAO-A and MAO-B. In the striatum of presymptomatic mice, some parameters (DA release and uptake, MAO-A activity) remained compensatory unchanged or compensatory decreased (MAO-B gene expression and activity), while others-a reduction in DA levels in tissue and extracellular space and in VMAT2 and DAT expression-manifest the functional failure. In symptomatic mice, only a few parameters (spontaneous DA release and uptake, MAO-B gene expression and activity) remained at the same level as at presymptomatic stage, while most parameters (DA level in tissue and extracellular space, DA-stimulated release, VMAT2 and DAT contents), decreased, showing decompensation, which was enhanced by increasing MAO-A activity. Thus, this study provides a comprehensive assessment of the molecular mechanisms of neuroplasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine models of preclinical and clinical stages of PD, which could potentially serve as a powerful tool for translational medicine.

Free radical production and antioxidant status in brain cortex non-synaptic mitochondria and synaptosomes at alcohol hangover onset

Alcohol hangover (AH) is the pathophysiological state after a binge-like drinking. We have previously demonstrated that AH induced bioenergetics impairments in a total fresh mitochondrial fraction in brain cortex and cerebellum. The aim of this work was to determine free radical production and antioxidant systems in non-synaptic mitochondria and synaptosomes in control and hangover animals. Superoxide production was not modified in non-synaptic mitochondria while a 17.5% increase was observed in synaptosomes. A similar response was observed for cardiolipin content as no changes were evidenced in non-synaptic mitochondria while a 55% decrease in cardiolipin content was found in synaptosomes. Hydrogen peroxide production was 3-fold increased in non-synaptic mitochondria and 4-fold increased in synaptosomes. In the presence of deprenyl, synaptosomal H2O2 production was 67% decreased in the AH condition. Hydrogen peroxide generation was not affected by deprenyl addition in non-synaptic mitochondria from AH mice. MAO activity was 57% increased in non-synaptic mitochondria and 3-fold increased in synaptosomes. Catalase activity was 40% and 50% decreased in non-synaptic mitochondria and synaptosomes, respectively. Superoxide dismutase was 60% decreased in non-synaptic mitochondria and 80% increased in synaptosomal fractions. On the other hand, GSH (glutathione) content was 43% and 17% decreased in synaptosomes and cytosol. GSH-related enzymes were mostly affected in synaptosomes fractions by AH condition. Acetylcholinesterase activity in synaptosomes was 11% increased due to AH. The present work reveals that AH provokes an imbalance in the cellular redox homeostasis mainly affecting mitochondria present in synaptic terminals.

Monoamine Oxidase Inhibitory Activity of Biflavonoids from Branches of Garcinia gardneriana (Clusiaceae)

Garcinia gardneriana is chemically characterized by the presence of biflavonoids. Taking into account that flavonoids are able to inhibit monoamine oxidase (MAO) activity, in the present study, the chemical composition of the branches' extract of the plant is described for the first time and the MAO inhibitory . activity of the isolated biflavonoids was evaluated. Based on spectroscopic and spectrometric data, it was possible to identify volkesiflavone, morelloflavone (1), Gb-2a (2) and Gb-2a-7-Ο-glucoside (3) in the ethyl acetate fraction from ethanol extract of the branches. Compounds 1-3 were evaluated in vitro and demonstrated the capacity to inhibit MAO-A activity with an IC₅₀ ranging from 5.05 to 10.7 μM, and from 20.7 to 66.2 μM for MAO-B. These inhibitions corroborate with previous IC₅₀ obtained for monomeric flavonoids, with a higher selectivity for MAO-A isoform. The obtained results indicate that biflavonoids might be promising structures for the identification of new MAO inhibitory compounds.

Does patchouli oil change blood platelet monoamine oxidase-A activity of adult mammals?

Patchouli oil, an essential aroma oil extracted from patchouli leaf during short-term exposure with five and ten drops either inhibited (at 1 or 2h) or stimulated (at 4h) the platelet MAO-A activity depending on the dosages of the aroma oil mainly due to inhibition or stimulation of its K m. The long-term 15 consecutive days exposure (with two or five drops) of patchouli oil, on the other hand, maximally stimulated the platelet MAO-A activity with five drops patchouli oil for 1h exposure, but further continuation of its exposure with same doses (two or five drops) for 30 consecutive days significantly stimulated (with two drops) and inhibited (with five drops) the platelet MAO-A activity due to stimulation and inhibition respectively of its correspondingboth K m and V max. These results thus suggest that this aroma oil exposure may modulate the blood platelet serotonergic regulation depending on the dose, duration, and conditions of exposure.

Indole-Substituted Benzothiazoles and Benzoxazoles as Selective and Reversible MAO-B Inhibitors for Treatment of Parkinson's Disease.

To develop novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was compound 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole with an IC50 value of 28 nM with no apparent effect on MAO-A activity at 10 μM. Based on the reversibility assay, compound 5b turned out to be fully reversible with over 95% of recovery of enzyme activity after washout of the compound. Compound 5b showed a reasonable stability in human liver microsomes and did not affect the activities of CYP isozymes, suggesting an absence of high-risk drug-drug interaction. In an in vivo MPTP-induced animal model of Parkinson's disease, oral administration of compound 5b showed neuroprotection of nigrostriatal dopaminergic neurons as revealed by tyrosine hydroxylase staining and prevention of MPTP-induced parkinsonism as revealed by motor behavioral assay of vertical grid test. In summary, the novel, reversible, and selective MAO-B inhibitor compound 5b was synthesized and characterized. We propose compound 5b as an effective therapeutic compound for relieving parkinsonism.

A Rhodium(III)-Based Inhibitor of Lysine-Specific Histone Demethylase 1 as an Epigenetic Modulator in Prostate Cancer Cells.

We report herein a novel rhodium(III) complex 1 as a new LSD1 targeting agent and epigenetic modulator. Complex 1 disrupted the interaction of LSD1-H3K4me2 in human prostate carcinoma cells and enhanced the amplification of p21, FOXA2, and BMP2 gene promoters. Complex 1 was selective for LSD1 over other histone demethylases, such as KDM2b, KDM7, and MAO activities, and also showed antiproliferative activity toward human cancer cells. To date, complex 1 is the first metal-based inhibitor of LSD1 activity.

Potent Selective Inhibition of Monoamine Oxidase A by Alternariol Monomethyl Ether Isolated from Alternaria brassicae.

Alternariol monomethyl ether (AME), a dibenzopyrone derivative, was isolated from Alternaria brassicae along with altertoxin II (ATX-II). The compounds were tested for the inhibitory activity of monoamine oxidase (MAO), which catalyzes neurotransmitting monoamines. AME was found to be a highly potent and selective inhibitor of human MAO-A with an IC50 value of 1.71 µM; however, it was found to be ineffective for MAO-B inhibition. ATX-II was not effective for the inhibition of either MAO-A or MAO-B. The inhibition of MAO-A using AME was apparently instantaneous. MAO-A activity was almost completely recovered after the dilution of the inhibited enzyme with an excess amount of AME, suggesting AME is a reversible inhibitor. AME showed mixed inhibition for MAO-A in Lineweaver-Burk plots with a Ki value of 0.34 µM. The findings of this study suggest that microbial metabolites and dibenzopyrone could be potent MAO inhibitors. In addition, AME could be a useful lead compound for developing reversible MAO-A inhibitors to treat depression, Parkinson's disease, and Alzheimer's disease.

Monoamine oxidase-A and B activities in the cerebellum and frontal cortex of children and young adults with autism.

Monoamine oxidases (MAOs) catalyze the metabolism of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine, and are key regulators for brain function. In this study, we analyzed the activities of MAO-A and MAO-B in the cerebellum and frontal cortex from subjects with autism and age-matched control subjects. In the cerebellum, MAO-A activity in subjects with autism (aged 4-38 years) was significantly lower by 20.6% than in controls. When the subjects were divided into children (aged 4-12 years) and young adults (aged 13-38 years) subgroups, a significant decrease by 27.8% in the MAO-A activity was observed only in children with autism compared with controls. When the 95% confidence interval of the control group was taken as a reference range, reduced activity of MAO-A was observed in 70% of children with autism. In the frontal cortex, MAO-A activity in children with autism was also lower by 30% than in the control group, and impaired activity of MAO-A was observed in 55.6% of children with autism, although the difference between the autism and control groups was not significant when all subjects were considered. On the contrary, there was no significant difference in MAO-B activity in both the cerebellum and frontal cortex between children with autism and the control group as well as in adults. These results suggest impaired MAO-A activity in the brain of subjects with autism, especially in children with autism. Decreased activity of MAOs may lead to increased levels of monoaminergic neurotransmitters, such as serotonin, which have been suggested to have a critical role in autism. © 2017 Wiley Periodicals, Inc.

The role of microsomal oxidation in the regulation of monoamine oxidase activity in the brain and liver of rats

It has been shown in our previous study that monoamine oxidase (MAO) activity in different brain regions are correlated with a microsomal oxidation phenotype. The data obtained in this study, using the microsomal oxidation inhibitor SKF525, and using animals with different duration of hexobarbital sleep, has shown that increased intensity of microsomal oxidation might be associated with increased MAO activity. Since the rats with short hexobarbital sleep time had higher content of hepatic microsomal cytochrome P450 than did rats with long hexobarbital sleep time. In addition, the rats with higher hepatic content of CYP450 had higher activities of MAO-A and MAO-B. Moreover, the microsomal oxidation inhibitor SKF-525 reduced brain and liver activities of MAOA and MAO-B. Consequently, MAO activities in a brain and a liver depend on the microsomal oxidation process.

MAO inhibitory activity of bromo-2-phenylbenzofurans: synthesis, in vitro study, and docking calculations.

Monoamine oxidase (MAO) is an enzyme responsible for metabolism of monoamine neurotransmitters which play an important role in brain development and function. This enzyme exists in two isoforms, and it has been demonstrated that MAO-B activity, but not MAO-A activity, increases with aging. MAO inhibitors show clinical value because besides the monoamine level regulation they reduce the formation of by-products of the MAO catalytic cycle, which are toxic to the brain. A series of 2-phenylbenzofuran derivatives was designed, synthesized and evaluated against hMAO-A and hMAO-B enzymes. A bromine substituent was introduced in the 2-phenyl ring, whereas position 5 or 7 of the benzofuran moiety was substituted with a methyl group. Most of the tested compounds inhibited preferentially MAO-B in a reversible manner, with IC50 values in the low micro or nanomolar range. The 2-(2'-bromophenyl)-5-methylbenzofuran (5) was the most active compound identified (IC50 = 0.20 μM). In addition, none of the studied compounds showed cytotoxic activity against the human neuroblastoma cell line SH-SY5Y. Molecular docking simulations were used to explain the observed hMAO-B structure-activity relationship for this type of compounds.

Novel 1-(2-pyrimidin-2-yl)piperazine derivatives as selective monoamine oxidase (MAO)-A inhibitors

In the present study, a new series of 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-substituted piperazine-1-carbodithioate derivatives (2a-n) were synthesized and screened for their monoamine oxidase A and B inhibitory activity. The structures of compounds were elucidated using spectroscopic methods and some physicochemical properties of new compounds were predicted using Molinspiration and MolSoft programs. Compounds 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-(4-nitrophenyl)piperazine-1-carbodithioate (2j) and 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-benzhydrylpiperazine-1-carbodithioate (2m) exhibited selective MAO-A inhibitory activity with IC50 = 23.10, 24.14 µM, respectively. Some of the biological results were found in accordance with the obtained in silico data based on Lipinski’s fule of five.

M21 - The Role of The Genetic Segments 5-Httlpr And Maoa In Moderating The Association Between Developmental Environment And Social And Emotional Abilities

Background 5-HTTLPR and MAOA, are genetic segments that influence serotonin and monoamine neurotransmitters. They were found to be associated with depression, suicidality, aggressiveness and anti-social behavior, with an evidence for a gene-environment (GXE) interaction. 5-HTTLPR was found to be associated with resilience to the effect of stressful life events on depression and suicidality, and MAOA was found to be associated with aggressiveness and anti-social behavior following childhood maltreatment. Findings demonstrated the negative aspect of this association, namely the interaction between a stressful environment and the gene, in a manner that reflects to pathology. Investigation of the positive end of the association has been the target of studies in more recent years, trying to prove that these are not vulnerability but plasticity genes. The aim of the current study was to further investigate the GXE interaction in this positive context. We hypothesized that 5HTTLPR and MAOA will moderate the relation between a good, beneficial environment and well-being. Methods 201 Israeli college students were recruited to the study, representing a normative, healthy population. The participants provided a saliva sample for DNA extraction and completed self- reported questionnaires measuring attachment, perceived social support, experience of life events, well-being and empathy. Genotyping was done using PCR methods for 2 well-studied functional polymorphisms: 5-HTTLPR and MAOA VNTR 1.1(635). 166 participants, who completed the questionnaire, and had at least one genetic result (out of two), were included in the final analysis. ANOVA, Pearson correlation and linear regression analysis were used to examine the correlation between explaining variables and outcome measures (well-being and empathy). Stratification according to genotype allowed the study of its moderating effect. Results No significant differences were found in measures of well-being and empathy between the 5-HTTLPR high activity group (LL genotypes) and low activity group (Ls or ss genotypes), or between the MAOA high, intermediate or low activity group (according to number of repeats). A significant association was found between one of the beneficial environment indices, the perceived support of friends, and the well-being score. This association was moderated by genotype. Individuals with the 5-HTTLPR short allele (s) or within MAOA intermediate and low activity groups were happier when they perceived higher support from their friends. This effect was not found for individuals with the long 5-HTTLPR allele (L) or individuals from the high MAOA activity. Discussion The current study demonstrated a GXE interaction, where genotype moderated the influence of perceived support of friends on happiness. Among the 5-HTTLPR long allele group, and MAOA high activity group, happiness was not influenced by the perceived support of friends, while among the 5-HTTLPR short allele group and MAOA intermediate and low group, happiness was higher when the perceived support of friends was higher. These results support the research hypothesis, according to which, these genetic polymorphisms provide their carriers with sensitivity to the environment, which exists also for a beneficial environment. Thus these genes confer not only resilience/vulnerability to stress as they were regarded in the past.

Selective inhibition of MAO-A activity results in an antidepressant-like action of 2-benzoyl 4-iodoselenophene in mice

Depression is a leading cause of disability worldwide. For this reason, the aim of this study was to investigate the possible antidepressant-like activity of 2-benzoyl-4-iodoselenophene (C17H11IOSe), a selenophene compound, in two well-consolidated behavioral assays for screening antidepressant activity (forced swimming test and tail suspension test) in mice. In order to investigate the mechanism of action of C17H11IOSe, it was investigated the activities of cerebral enzymes: monoamine oxidase MAO A and B and Na+, K+ ATPase, and if an inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA) (100mg/kg) blocks the antidepressant-like effect of C17H11IOSe. Swiss mice received (C17H11IOSe) (5–50mg/kg) or canola oil by the intragastric (i.g.) route before behavioral tests. The results showed that C17H11IOSe at dose range of 5–50mg/kg decreased immobility time in the tail suspension test. In the forced swimming test, C17H11IOSe reduced the immobility time at the doses of 10 and 50mg/kg. C17H11IOSe differently affected the cerebral cortical Na+, K+ ATPase; the effects on this enzyme were dependent of the dose tested. At a dose of 10mg/kg, the compound increased Na+, K+ ATPase activity, while the activity was inhibited at a dose of 50mg/kg. pCPA blocked the antidepressant-like action of C17H11IOSe in mice. Therefore, C17H11IOSe (5–50mg/kg) selectively inhibited MAO-A activity in cerebral cortices of mice. The modulation of serotonergic system contributed to the antidepressant-like action of C17H11IOSe in mice.

Neuroprotective Effect of a New 7,8-Dihydroxycoumarin-Based Fe2+/Cu2+ Chelator in Cell and Animal Models of Parkinson's Disease.

Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson's disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical, and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu2+ ∼ Fe2+ > Zn2+ > Fe3+. No binding capacity was detected for Hg2+, Co2+, Ca2+, Mn2+, Mg2+, Ni2+, Pb2+, or Cd2+. DHC12 accessed cells colocalizing with Mitotracker Orange, an indication of mitochondrial targeting. In addition, DHC12 chelated mitochondrial and cytoplasmic labile iron. Upon mitochondrial complex I inhibition, DHC12 protected plasma membrane and mitochondria against lipid peroxidation, as detected by the reduced formation of 4-hydroxynonenal adducts and oxidation of C11-BODIPY581/591. DHC12 also blocked the decrease in mitochondrial membrane potential, detected by tetramethylrhodamine distribution. DHC12 inhibited MAO-A and MAO-B activity. Oral administration of DHC12 to mice (0.25 mg/kg body weight) protected substantia nigra pars compacta (SNpc) neurons against MPTP-induced death. Taken together, our results support the concept that DHC12 is a mitochondrial-targeted neuroprotective iron-copper chelator and MAO-B inhibitor with potent antioxidant and mitochondria protective activities. Oral administration of low doses of DHC12 is a promising therapeutic strategy for the treatment of diseases with a mitochondrial iron accumulation component, such as PD.

233 - Evaluation of Biological Activities of Hypericum Perforatum L. and Hypericum Calycinum L. Extracts

The genus Hypericum (Clusiaceae) consists of 450 species of herbs, shrubs and trees worldwide. In Turkey, it is represented by 89 species of which 43 are endemic. Hypericum perforatum L. commonly known as St. John’s Wort is used traditionally to treat several neurological disorders such as neuralgia, anxiety, mild to moderate depression also externally to treat wounds. In the present work, the aqueous-ethanolic extracts of the aerial parts of Hypericum perforatum L. and H. calycinum L. were searched for antioxidant capacity and acetylcholinesterase (ACE), butyrylcholinesterase (BCE), cyclooxygenase COX-1 and COX-2, and also monoamine oxidase MAO-A and MAO-B inhibitory activities. Total phenolic contents of the extracts were determined by using Folin-Ciocalteu assay. According to the antioxidant activity results, H. calycinum showed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity with an inhibition of 50.61±2.8% than H. perforatum (44.85±1.8%) when compared to BHT 54.28±1.04% and ascorbic acid 72.25±1.35%. At the concentration of 0.5 mg/ml, chelating abilities of H. perforatum and H. calycinum on ferrous ions were 20.7% and 24.5% respectively whereas EDTA showed 89.2% chelating activity. Both H. perforatum and H. calycinum extracts showed significant ferric-reducing power with EC50 values of 0.26 and 0.24 (BHT (EC50 0.2)) and ABTS radical cation decolorization activity with inhibitions of 56.9% and 68.7% (Trolox (79.01%)). H. perforatum showed 28.87% ACE, 20.46% BCE, 31.50% COX-1, 29.03% COX-2, 47.00% MAO-A and 36.32% MAO-B inhibitory activities whereas H. calycinum showed 30.45% ACE, 25.08% BCE, 34.15% COX-1, 39.79% COX-2, 59.77% MAO-A and 38.88% MAO-B inhibitory activities. H. calycinum had higher total phenolic content (313.94 mg gallic acid equivalent/100 g) than H. perforatum (308.83 mg gallic acid equivalent/100 g).

Pain-depression dyad induced by reserpine is relieved by p,p'-methoxyl-diphenyl diselenide in rats

Depression and pain comorbidity represent a neuropsychiatric condition with substantial socioeconomic impact to society. The commonly used antidepressants and analgesics to treat this comorbidity have shown restricted clinical efficacy. In this way, the aim of this study was to investigate the behavioral, biochemical and neurochemical effects of a p,p'-methoxyl-diphenyl diselenide (OMePhSe)2 supplemented diet on pain-depression dyad induced by reserpine in rats. Adult Wistar rats were fed with 10mg (MeOPhSe)2 per kg of rat chow supplemented diet for 30 days. Pain-depression dyad was induced by daily subcutaneous reserpine injection (0.5mg/kg for three consecutive days) from 22 to 24 day of (MeOPhSe)2 supplementation. The results showed that the reserpine injected rats had behavior phenotypes typical of depression-pain dyad and the (MeOPhSe)2-supplemented diet protected against these modifications. Furthermore, the (MeOPhSe)2 dietary supplementation was effective against the increase in the prefrontal cortical MDA levels caused by reserpine. (MeOPhSe)2-supplemented diet triggered a per se augmentation of Nrf-2 levels. The [3H] serotonin uptake, [3H] glutamate uptake and release and MAO activity were not altered in the prefrontal cortices of rats from any experimental group. Therefore, the results indicate that protective effects of a (MeOPhSe)2-supplemented diet can be mediated, at least in part, by its antioxidant property.

P.7.d.003 - Polyunsaturated omega-3 fatty acids are not effective for depressive and compulsive symptoms in adolescent girls with anorexia nervosa

Depression and pain comorbidity represent a neuropsychiatric condition with substantial socioeconomic impact to society. The commonly used antidepressants and analgesics to treat this comorbidity have shown restricted clinical efficacy. In this way, the aim of this study was to investigate the behavioral, biochemical and neurochemical effects of a p,p'-methoxyl-diphenyl diselenide (OMePhSe)2 supplemented diet on pain-depression dyad induced by reserpine in rats. Adult Wistar rats were fed with 10 mg (MeOPhSe)2 per kg of rat chow supplemented diet for 30 days. Pain-depression dyad was induced by daily subcutaneous reserpine injection (0.5 mg/kg for three consecutive days) from 22 to 24 day of (MeOPhSe)2 supplementation. The results showed that the reserpine injected rats had behavior phenotypes typical of depression-pain dyad and the (MeOPhSe)2-supplemented diet protected against these modifications. Furthermore, the (MeOPhSe)2 dietary supplementation was effective against the increase in the prefrontal cortical MDA levels caused by reserpine. (MeOPhSe)2-supplemented diet triggered a per se augmentation of Nrf-2 levels. The [3H] serotonin uptake, [3H] glutamate uptake and release and MAO activity were not altered in the prefrontal cortices of rats from any experimental group. Therefore, the results indicate that protective effects of a (MeOPhSe)2-supplemented diet can be mediated, at least in part, by its antioxidant property.