MAO Activity Research Articles

Synthesis of 2′-(1,2,3-triazoyl)-acetophenones: molecular docking and inhibition ofin vitromonoamine oxidase activity

The synthesis of 2′-(1,2,3-triazoyl)-acetophenones by a CuAAC using thiourea as a ligand, molecular docking and MAO activity analyses were performed.

Intramolecular charge transfer enhancing strategy based MAO-A specific two-photon fluorescent probes for glioma cell/tissue imaging.

MAO-A promotes the proliferation of human glioma cells. Herein, we report a series of MAO-A specific two-photon small molecular fluorescent probes (A1-5) based on an intramolecular charge transfer enhancing strategy. The activity of endogenous MAO-A can be selectively imaged using A3 as a representative probe in different biological samples including human glioma cells/tissues via two-photon fluorescence microscopy. The study provides new tools for the visual detection of glioma.

Medicinal Properties of Asparagus

Asparagus ia a vegetable and a medicinal or traditional herb. It has many health benefits because of its pharmacological properties and the active ingredients responsible for its effectiveness against various illnesses. A few medicinal Properties are discussed below:
 Anti-Inflammation Property of Asparagus
 Anti-inflammation can be defined as “It acts on body responses and reduce the inflammation, without directly counteracting the active agent such as glucocorticoids and aspirin”. One of these saponins has been of unique exuberance for relationship to amyotrophic horizontal sclerosis, otherwise called Lou Gehrig's Disease [1]. Even however amyotrophic parallel sclerosis is delegated a perpetual, neurodegenerative illness and isn't right now acknowledged as an immune system issue, over the top, undesirable irritation may assume an imperative part in the passing of certain nerve cells in amyotrophic sidelong sclerosis. In this mitigating setting, it is important that current research on the shatavarins in asparagus has uncovered another assemblage of saponins that impact aggravation through cytokine informing [2].
 Asparagus as the Best Antioxidant
 Analysts in Brazil has estimated the general reinforcement limit of asparagus. These specialists broke down twenty three ordinarily eaten vegetables in Brazil including asparagus. Their general outcomes demonstrated turmeric, watercress, lettuces, and broccoli to give the best general cancer prevention agent limit. Be that as it may, in a portion of the vegetables testing, asparagus turned out in the best ten among each of the twenty three vegetables for general cancer prevention agent limit. This finding isn't astonishing, given thenumerous customary and offbeat cell reinforcements show in asparagus. It merits recollecting here that asparagus positions as an astounding wellspring of both vitamin E and vitamin C two spotlight antioxidantas well as the mineral selenium, which assumes a key part in the capacity of glutathione peroxidase a standout amongst the most-examined cell reinforcement proteins in the body [3].The impact of methanolic concentrate of Asparagus pubescens was explored on compound, warm actuated agony and new egg whites incited aggravation. The concentrate measurement conditionally pent-up acidic corrosive incited wiggling, formalin-initiated torment licking and hot plate-actuated agony in mice. The concentrate essentially hindered the new egg whites prompted irritation in rats also. These hindrances were measurably critical [4].
 Antidepressant Activity
 The methanolic extract of asparagus demonstrated a decrease in immobility time in FST and TST in mice, which was comparable to imipramine and increase the levels of dopamine in vitro [5]. Futhermore, it was found to significantly brain monoamine oxidase levels as compared to control in a study focusing on finding the underlying mechanism of action, it was seen that methanolic extracts significantly inhibited cholinesterase and MAO activities [6]. In another study, antidepressant like activity was seen with methanolic root extract in FST and learned helplessness model [7].
 Anti Amnesic Activity
 Ethanolic root extract of asparagus was observed to produce a significant dose dependent enhancement of memory in the elevated plus maze model in mice [8]. The effect being significantly higher then the produced by piracetam [9]. Also there was an increase in the acetylcholinestrease levels in hippocampus areas associated with learning and memory [10]. In another study, methanolic exracts was found to reverse amnesia produced by scopolamine and sodium nitrate in the EPM and Morris water maze model in mice [11].
 Analgesic Action
 Aqueous and alcohalic root extracts of asparagus has been found to produce indicative analgesic action in heat conduction model. In another study, ethanolic extracts of asparagus was found to inhibit writing reflex in acetic acid induced writing model in mice [12].
 Antipyretic Action
 The ethanolic extracts of asparagus showed significant more antipyretic activity in albino Wistar rats than the aqueous extract in the yeast-derived pyrexia model, an effect comparable to normal antipyretic paracetamol [13]. Asparagus root extract which contains highest amount of flavonoids, polyphenols and vitamin-C exhibits the greatest antioxidant activity. Asparagus is likewise rich in flavonoid rutin
 REFERENCES

Increased MAO-A Activity Promotes Progression of Pulmonary Arterial Hypertension.

Monoamine oxidases (MAOs), a class of enzymes bound to the outer mitochondrial membrane, are important sources of reactive oxygen species. Increased MAO-A activity in endothelial cells and cardiomyocytes contributes to vascular dysfunction and progression of left heart failure. We hypothesized that inhibition of MAO-A can be used to treat pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. MAO-A levels in lung and RV samples from patients with PAH were compared with levels in samples from donors without PAH. Experimental PAH was induced in male Sprague-Dawley rats by using Sugen 5416 and hypoxia (SuHx), and RV failure was induced in male Wistar rats by using pulmonary trunk banding (PTB). Animals were randomized to receive either saline or the MAO-A inhibitor clorgyline at 10 mg/kg. Echocardiography and RV catheterization were performed, and heart and lung tissues were collected for further analysis. We found increased MAO-A expression in the pulmonary vasculature of patients with PAH and in experimental experimental PAH induced by SuHx. Cardiac MAO-A expression and activity was increased in SuHx- and PTB-induced RV failure. Clorgyline treatment reduced RV afterload and pulmonary vascular remodeling in SuHx rats through reduced pulmonary vascular proliferation and oxidative stress. Moreover, clorgyline improved RV stiffness and relaxation and reversed RV hypertrophy in SuHx rats. In PTB rats, clorgyline had no direct clorgyline had no direct effect on the right ventricle effect. Our study reveals the role of MAO-A in the progression of PAH. Collectively, these findings indicated that MAO-A may be involved in pulmonary vascular remodeling and consecutive RV failure.

Cerebroprotective effects of D. triquetrum on sodium nitrite‐induced hypoxia and ethanol‐induced neurodegeneration in animal models relevant to dementia

AbstractBackgroundCognitive impairment is a multidimensional and complicated concept that subsumes the attention, concentration, learning, memory, problem‐solving ability, visuospatial abilities, mental flexibility, psychomotor efficiency and manual dexterity.ObjectiveTo study the effects of aqueous extracts of roots of Desmodium triquetrum on cognitive deficit mice.MethodsAqueous extracts of Desmodium triquetrum (DTE) were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models such as rotarod, Passive shock avoidance paradigm, special water bottle case model, elevated plus maze and Morris water maze. DTE (5, 2.5 and 1.25 mg/kg p.o.) were administered to the mice. Acquisition, retention, Transfer latency (TLT), Time spent in target quadrant (TSTQ), Step down latency (SDL) and Escape latency (ELT) and biochemical parameters such as AChE, MAOA, TBARS, epinephrine, 5 HT were determined. DNA fragmentation studies were conducted which were compared with Donepezil.ResultsDTE (5, 2.5 and 1.25 mg kg(‐1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. DTE improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transfer Latency Time (TLT), escape latency time, TSTQ and increased the Step Down Latency (SDL. DTE inhibited Acetylcholinestrase (p < 0.01) activity, increased GSH, decreased TBARS and inhibited MAOA activity. Reduced the metabolism of epinephrine, 5‐HT. DTE (5 mg kg‐1) protected the DNA fragmentation of frontotemporal cortex from hypoxic effects.ConclusionDesmodium triquetrum are beneficial in the management of Neurodegenerative disorders particularly for Alzheimer’s disease.

Enhanced Catecholamine Flux and Impaired Carbonyl Metabolism Disrupt Cardiac Mitochondrial Oxidative Phosphorylation in Diabetes Patients.

Aims: Catecholamine metabolism via monoamine oxidase (MAO) contributes to cardiac injury in models of ischemia and diabetes, but the pathogenic mechanisms involved are unclear. MAO deaminates norepinephrine (NE) and dopamine to produce H2O2 and highly reactive "catecholaldehydes," which may be toxic to mitochondria due to the localization of MAO to the outer mitochondrial membrane. We performed a comprehensive analysis of catecholamine metabolism and its impact on mitochondrial energetics in atrial myocardium obtained from patients with and without type 2 diabetes. Results: Content and maximal activity of MAO-A and MAO-B were higher in the myocardium of patients with diabetes and they were associated with body mass index. Metabolomic analysis of atrial tissue from these patients showed decreased catecholamine levels in the myocardium, supporting an increased flux through MAOs. Catecholaldehyde-modified protein adducts were more abundant in myocardial tissue extracts from patients with diabetes and were confirmed to be MAO dependent. NE treatment suppressed mitochondrial ATP production in permeabilized myofibers from patients with diabetes in an MAO-dependent manner. Aldehyde dehydrogenase (ALDH) activity was substantially decreased in atrial myocardium from these patients, and metabolomics confirmed lower levels of ALDH-catalyzed catecholamine metabolites. Proteomic analysis of catechol-modified proteins in isolated cardiac mitochondria from these patients identified >300 mitochondrial proteins to be potential targets of these unique carbonyls. Innovation and Conclusion: These findings illustrate a unique form of carbonyl toxicity driven by MAO-mediated metabolism of catecholamines, and they reveal pathogenic factors underlying cardiometabolic disease. Importantly, they suggest that pharmacotherapies targeting aldehyde stress and catecholamine metabolism in heart may be beneficial in patients with diabetes and cardiac disease. Antioxid. Redox Signal. 35, 235-251.

P.760 Effects of novel cholinesterase inhibitors on mitochondrial respiration and MAO activity - in vitro study

Based on the lately identified role for the interstitial cells of Cajal (ICCs) of mouse prostate in catecholamine production, as well as the well-established role for the master coregulator metastasis-associated protein 1 (MTA1) in inflammation, we probed into the functional link between aberrant MTA1 expression and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using both a MTA1−/− mouse model of experimental autoimmune prostatitis (EAP) and an in vitro chronic prostatitis model in cultured murine ICCs. EAP-induced MTA1 expression was enriched in ICCs of mouse prostate. EAP resulted in a higher increase in the pelvic pain response in MTA1−/− mice compared to WT mice. Consistently, the ICCs from MTA1−/− mice produced higher levels of catecholamines upon induction of in vitro chronic prostatitis. Mechanistically, MTA1 could directly suppress the transcription of Aadc, a rate-limiting enzyme during catecholamine synthesis, in a HDAC2-depdendent manner. Importantly, treatment with AADC inhibitor NSD-1015 significantly ameliorated EAP-elicited pain response and catecholamine overactivity in MTA1−/− mice. Taken together, our findings reveal an inherent regulatory role of the MTA1/AADC pathway in the maintenance of catecholamine production homeostasis in prostate ICCs, and also point to a potential use of HDAC inhibitors and/or AADC inhibitors to treat CP/CPPS.

Is there a relationship between morphological and functional platelet changes and depressive disorder?

Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder. According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1) platelets in depression [Title/Abstract]"; (2) "(platelets[Title]) AND depressive disorder[Title/Abstract]"; (3) "(Platelet[Title]) AND major depressive disorder[Title]"; (4) (platelets[Title]) AND depressed[Title]"; (5) (platelets[Title]) AND depressive episode[Title]"; (6) (platelets[Title]) AND major depression[Title]"; (7) platelet activation in depression[All fields]"; and (8) platelet reactivity in depression[All fields]." After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2A receptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways. Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.

Emodin Derivatives as Multi-Target-Directed Ligands Inhibiting Monoamine Oxidase and Antagonizing Vasopressin V1A Receptors.

The brain neurotransmitter level is associated with the pathology of various neurodegenerative diseases, and age-dependent increase in the blood level of vasopressin, human brain monoamine oxidase (hMAO) level, oxidative stress, and imbalance in aminergic signaling are common disease-modifying factors leading to various neurodegenerative disorders. Based on the reports of emodin in hMAO inhibition and antagonist effect on the vasopressin V1A receptor, in this study we synthesized six emodin derivatives and evaluated their effects on MAO activity and G protein-coupled receptors. Among them, 4-hydroxyemodin and 5-hydroxyemodin were potent inhibitors of hMAO, and 2-hydroxyemodin and 5-hydroxyemodin were good V1AR antagonists. In silico molecular docking simulation revealed that the hydroxyl group at C2, C4, and C5 of the respective compounds interacted with prime residues, which corroborates the in vitro effect. Likewise, these three derivatives were predicted to have good drug-like properties. Overall, our study demonstrates that the hydroxyl derivatives of emodin are multi-target-directed ligands that may act as leads for the design and development of a therapy for central nervous system disorders.

Skimmetin/osthole mitigates pain-depression dyad via inhibiting inflammatory and oxidative stress-mediated neurotransmitter dysregulation

Pain and depression are often co-existing pathological states that promote mutual severity resulting in limited efficacy of current treatment strategies. Thus, there is a need to develop an efficacious alternate treatment regimen for pain-depression dyad. Skimmetin and osthole are molecules of natural origin that have been explored for an anti-hyperglycemic, anti-bacterial, anti-fungal, and anti-diabetic activities in preclinical studies. in animal models. The current study has been designed to explore the beneficial effect of skimmetin/osthole in reserpine-induced pain-depression dyad in mice. Female Swiss albino mice (n = 6) were challenged with reserpine (0.5mg/kgs.c.) for the first 3days to induce a pain-depression dyad-like state. Skimmetin (10mg/kgi.p.) and osthole (10mg/kgi.p.) were administered for 5days consecutively, starting from the first day of study. Reserpine treatment significantly reduced the pain threshold in the pressure application measurement (PAM) and electronic von frey (eVF) test. In forced swim test (FST) and Morris water maze (MWM) test mice displayed an increased immobility time and latency to reach platform respectively. Biochemical results showed an increased level of TNF-α, IL-1β, TBARS, glutamate, and reduced level of GSH, norepinephrine, and serotonin in the reserpine treated group. Reserpine treatment also increased brain MAO-A activity. Skimmetin/osthole treatment was found to attenuate the behavioral and biochemical alterations induced by reserpine. The results of the current investigation delineated that skimmetin/osthole may exert anti-nociceptive, anti-depressant, and improved cognition via inhibiting inflammatory and oxidative stress-mediated neurotransmitter dysregulation.

Dietary monosodium glutamate altered redox status and dopamine metabolism in lobster cockroach (Nauphoeta cinerea).

Monosodium Glutamate (MSG) is the most commonly utilized food additive in the world. However, data on possible biochemical reasons underlying the neurotoxic effects of dietary MSG is limited. Therefore, this study investigated the effects of dietary supplementation of MSG on redox status and neurochemical indices in lobster cockroach nymph. These were evaluated via assessment of enzymatic and nonenzymatic antioxidants, acetylcholinesterase and monoamine oxidase activities, and dopamine content in the cockroach nymph head homogenate. MSG supplemented diet caused dose-dependent significant (p<.05) reduction in % survival, thiol, GSH, dopamine contents, and GST activity, increased ROS, NO, Fe2+ , MDA contents, and MAO activity but no significant (p<.05) difference was obtained in GSH and TBARS contents, and AChE activity. Increased oxidative, cholinergic, and monoaminergic activities coupled with decreased dopamine level might be the plausible biochemical explanation for the neurotoxic effects observed during sub-chronic consumption of large amounts of MSG in diet. PRACTICAL APPLICATIONS: This study suggests that consumption of monosodium glutamate should be reduced to the barest minimum due to its capability to induce oxidative stress and nervous toxicological effects at high dosage.

Kava decreases the stereotyped behavior induced by amphetamine in mice

Ethnopharmacological relevanceKava extract (Piper methysticum) is a phytotherapic mainly used for the treatment of anxiety. Although the reported effects of Kava drinking improving psychotic symptoms of patients when it was introduced to relieve anxiety in aboriginal communities, its effects on models of psychosis-like symptoms are not investigated. Aim of the studyTo investigate the effects of Kava extract on behavioral changes induced by amphetamine (AMPH) and its possible relation with alterations in monoamine oxidase (MAO) activity. Materials and methodsMice received vehicle or Kava extract by gavage and, 2 h after vehicle or AMPH intraperitoneally. Twenty-five minutes after AMPH administration, behavioral (elevated plus maze, open field, stereotyped behavior, social interaction and Y maze) and biochemical tests (MAO-A and MAO-B activity in cortex, hippocampus and striatum) were sequentially evaluated. ResultsKava extract exhibited anxiolytic effects in plus maze test, increased the locomotor activity of mice in open field test and decreased MAO-A (in cortex) and MAO-B (in hippocampus) activity of mice. Kava extract prevented the effects of AMPH on stereotyped behavior and, the association between Kava/AMPH increased the number of entries into arms in Y maze test as well as MAO-B activity in striatum. However, Kava extract did not prevent hyperlocomotion induced by AMPH in open field test. The social interaction was not modified by Kava extract and/or AMPH. ConclusionThe results showed that Kava extract decreased the stereotyped behavior induced by AMPH at the same dose that promotes anxiolytic effects, which could be useful to minimize the psychotic symptoms in patients.

Chronic Exposure to WIN55,212-2 During Adolescence Alters Prefrontal Dopamine Turnover and Induces Sensorimotor Deficits in Adult Rats.

Several lines of evidence suggest that chronic exposure to cannabinoids during adolescence may increase the risk of schizophrenia. Studies of the disorder have identified altered cortical dopaminergic neurotransmission. In this study, we hypothesised that heightened endocannabinoid system activation via chronic exposure to a highly potent cannabinoid receptors agonist in adolescent rats would cause long-lasting neurobiological changes that may dramatically alter expression and functions of dopamine metabolising enzymes, comethyl-o-transferase (COMT) and monoamine oxidases MAO-A and MAO-B. To test this hypothesis, adult male rats (70 PND) undergoing chronic treatment of the highly potent and non-selective CB agonist WIN55,212-2 (1.2mg/kg) during adolescence (PND 30-50) were subjected after 20days washout period to prepulse inhibition of acoustic startle test (PPI) to confirm cannabinoid-induced sensorimotor-gating impairments and afterwards examined for COMT, MAO-A and MAO-B expression and activity in the prefrontal cortex. Chronic WIN55,212-2 exposure during adolescence caused disruption of PPI, increased cortical dopamine level, decreased COMT mRNA expression and decreased MAO-A and MAO-B enzymatic activities. These results indicate that chronic exposure to cannabinoids during adolescence induces sensorimotor-gating alterations which likely result from changes in the prefrontal cortex dopaminergic signalling. This has important implications for developing methods of targeting dopamine metabolising enzymes and/or sequelae of its dysregulation in cannabinoid-induced schizoaffective-like behaviour.

Evaluation of antidepressant activity of methanolic and hydroalcoholic extracts of Acorus calamus L. rhizome through tail suspension test and forced swimming test of mice

Acorus calamus (AC) L. (Araceae) is an annual semi-aquatic and aromatic plant found in Europe, North America and Asia. Its rhizomes are often used by Native Americans, Americans, and Chinese as well as by other cultures. Ethnobotanical studies and documents have shown their use in various disease treatments, such as insomnia, mental disorders, diabetes mellitus, epilepsy, inflammation, asthma, neuropathic pain, and diarrhea. In this study, the antidepressant activity of methanolic and hydroalcoholic extracts of the AC rhizome part in mice was investigated. Three doses of methanolic extract of AC rhizome (MEACR) (25, 50 and 100 mg/kg b.wt), three doses of hydroalcoholic extract of AC rhizome (HAACR) (100, 200 and 400 mg/kg b.wt), and standards (imipramine, 15 mg/kg b.wt and fluoxetine, 20 mg/kg b.wt) was daily oral administration to the mice for consecutive 14 days. The extract effect on the immobility time was monitored by a tail suspension test (TST) and a forced swimming test (FST). Monoamine oxidase (MAO) levels were also analyzed using standard methods. The optimum antidepressant activity was viewed at 100 mg/kg b.wt of MEACR extract and 400 mg/kg b.wt of HAACR extract with 23.82% and 20.59% immobility period reduction, respectively. Besides, the extracts weakened the FST-induced elevation of MAO activity significantly and returned to near-normal levels of neurotransmitters in the brain. 100 mg/kg b.wt or above of MEACR extract significantly prevented the MAO-A and MAO-B activities in mice brain at a dose-dependent fashion. But, just 400 mg/kg b.wt of HAACR extract prevented the activity of MAO-A and MAO-B. Fluoxetine and imipramine showed a tendency to prevent the activity of MAO-A and MAO-B. This study suggests that AC rhizome extract mediated antidepressant activity by modulating the central neurochemical and hypothalamic-pituitary-adrenal (HPA) axis in response to FST and TST-induced stress. Therefore, AC rhizome extract can be used as a valuable plant supplement to treat depressive disorders.

Abstract 421: Norepinephrine Catabolism Drives Cardiac Fibroblast Activation via Monoamine Oxidase Activity and Rage/β-adrenergic Signaling

The mitochondrial enzyme monoamine oxidase A (MAO-A) plays an increasingly appreciated role in cardiac remodeling induced by diabetes and ischemic injury. Oxidative deamination of norepinephrine (NE) by MAO-A generates 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) and H 2 O 2 . Isolation and quantification of catechol-modified proteins from cardiac fibroblast lysate using an aminophenylboronic acid resin showed an MAO-dependent accumulation of catechol adducts in NE-treated cells (P&lt;0.05). Our lab has previously observed increased expression and activity of MAO in myocardium of diabetes patients compared with age-matched nondiabetic patients. Moreover, preliminary data suggest that catecholaldehydes and other biogenic aldehydes might contribute to the pathogenesis of cardiac fibrosis in diabetic cardiomyopathy via pro-fibrotic signaling mechanisms. We hypothesize that NE activates fibroblasts by both canonical pathways (i.e, adrenergic receptors) and by monoamine oxidase-mediated catabolism and activation of the receptor for advanced glycation endproducts (RAGE). Treatment of cardiac fibroblasts with NE (1 μM) resulted in accelerated proliferation, enhanced collagen I &amp; III secretion, robust increases in mitochondrial and total cellular ROS, and upregulated pro-fibrotic gene expression. These effects were abrogated by co-administration of RAGE antagonist FPS-ZM1, MAO inhibitors, β-blocker propranolol, and the aldehyde scavenger carnosine (P&lt;0.05). These findings suggest that NE (and other catecholamines) may influence extracellular matrix remodeling via multiple pathways, including adrenergic and also RAGE, via MAO-mediated catabolism.

Synthesis of palladium complexes with quinolino-based tridentate ligands and their applications for norbornene polymerization

Palladium complexes bearing new tridentate quinolino-based [N−NNox] ligands were synthesized and tested for the polymerization of norbornene. Upon activation of MAO, all the palladium complexes showed high catalytic activities for the vinyl-addition polymerization of norbornene up to 11.5 × 106 g of PNB (mol of Pd)−1h−1. The structure–activity relationships in the polymerization of norbornene, namely steric and electric effects of the ligands, were carefully investigated.

Naringin regulates erectile dysfunction by abolition of apoptosis and inflammation through NOS/cGMP/PKG signalling pathway on exposure to Bisphenol-A in hypertensive rat model

This study investigated the effect of naringin (NRG) on extracellular metabolism of ATP through the NOS/cGMP/PKG signaling pathway induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) on exposure to Bisphenol-A (BPA) in penis. Fifty-six adult male albino rats were randomly distributed into eight (n = 7) groups. Group I: control animals, Group II was treated with 40 mg/kg L-NAME, Group III was treated with 50 mg/kg BPA, Group IV was treated with 40 mg/kg L-NAME +50 mg/kg BPA. Group V was administered with 40 mg/kg L-NAME +80 mg/kg NRG. Group VI was administered with 50 mg/kg BPA + 80 mg/kg NRG. Group VII was administered with 40 mg/kg L-NAME+50 mg/kg BPA + 80 mg/kg NRG. Lastly, group VIII was treated with 80 mg/kg NRG for 14 days. NRG prevented hypertension and erectile dysfunction by inhibiting the activities of angiotensin-converting enzymes, arginase, and phosphodiesterase-51 (PDE-51) with corresponding down-regulation of inflammatory markers including TNF-α and IL-B. Additionally, hypertensive erectile dysfunction was remarkably prevented by NRG as manifested by the declined activities of AChE, MAO-A and enzymes of ATP hydrolysis (ATPase, ADPase, AMPase and ADA) with resultant increase in NO level. Also, penile expression of antigen presenting cells, CD43 transcript, caspace-9 and tumor suppressor P53 proteins were repressed on treatment with NRG. This study validates the hypothesis that NRG may be a valuable remedy in abrogating penile inflammatory markers, apoptosis and enzymes of ATP-hydrolysis via NOS/cGMP/PKG signaling pathways in hypertensive rat model on exposure to environmental toxicant.

Efficacy of arecoline hydrobromide against cattle tick Rhipicephalus (Boophilus) microplus

ABSTRACT The objective of the present study was to determine the efficacy of arecoline hydrobromide against Rhipicephalus (Boophilus) microplus. Larval packet test (LPT) was performed on larvae produced from collected ticks. Adult immersion test (AIT) was performed to determine live tick weight, the mortality of ticks, and inhibition of oviposition and hatching after arecoline application. Arecoline was taken in different concentrations (i.e. 0.1, 0.5, 1.5, 2.5 5, 7.5, 10 and 12.5 mg/mL) to evaluate its acaricidal activity. The result of LPT exhibited 100% mortality of larvae at 12.5 mg/mL concentration of arecoline. AIT results showed that arecoline caused 87.90% mortality in its highest dose, reduction of egg weight (0.031 g) and excessively reduced hatch rates (2.03%) in ticks as compared to the control group. The level of protective enzymes (SOD and GST) was found to decrease when a reduction in the activity of MAO and AChE enzymes were achieved. It can be concluded from the study that arecoline possess significant acaricidal and oxidative stress-inducing activities in the cattle tick R. microplus. It can be developed as an herbal acaricide in place of synthetic drugs that harm living beings and the environment.

Effect of 3-Oxypyridine Derivatives and Succinic Acid on the Activity of Monoamine Oxidases and the Content of Monoamines in the Hypothalamus of Rats with Alloxan-Induced Diabetes

Abstract—We studied the effect of novel domestic derivatives of 3-oxypyridine and succinic acid (emoxypine, reamberin, and mexidol) on the activity of monoamine oxidases (MAO-A and MAO-B) and the level of biogenic amines (serotonin and dopamine) in the hypothalamus during the first two weeks of alloxan-induced diabetes in rats. During the first 14 days of alloxan-induced diabetes in rats, the levels of serotonin and dopamine decreased in the hypothalamus in the presence of unchanged MAO-B activity. The MAO-A activity and serotonin level in the hypothalamus of diabetic rats did not differ from the control values ​​at the initial stage of the experiment, and after a significant transient decrease, they again reached normal levels. The dopamine level in the hypothalamus of rats with experimental diabetes decreased only at the end of the experiment. The application of the studied drugs at doses equivalent to the therapeutic range for humans corrected the transient shifts in MAO-A activity and the delayed deficiency of monoamines in the hypothalamus of animals with alloxan-induced diabetes. The seven-day administration of an isolated derivative of 3-oxypyridine (emoxypine) and an isolated derivative of succinic acid (reamberin) prevented the transient decrease in MAO-A activity, compensated the concomitant deficiency of serotonin and increased the dopamine level in the hypothalamus of rats with alloxan-induced diabetes. Mexidol, which is simultaneously a derivative of 3‑oxypyridine and succinic acid, prevented a decrease in the hypothalamic levels of serotonin and dopamine in diabetic rats after 7 and 14-fold use (respectively). Correction of hypothalamic serotonin deficiency by Mexidol was not accompanied by changes in the activity of MAO-A and MAO-B. A decrease in hypothalamic dopamine deficiency as a result of a two-week administration of Mexidol was accompanied by a decrease in MAO-A activity. The intensity of neurochemical effects induced by derivatives of 3-oxypyridine and succinic acid were similar to α-lipoic acid which was used as a comparison drug.

Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence.

The present study combined the analysis of two transcriptional regulators, uVNTR and dVNTR, in the MAOA gene that is an enzyme responsible for the monoamine degradation and identified genetic interaction between these VNTRs in association with the nicotine dependence. The main impact is that when analyzing different populations in the genetic studies, the functionally meaningful variants should be combined rather than addressing individual elements separately (a mini polygenic risk score for a particular gene/locus). This combination is very rarely analyzed and therefore the study sets an example. Another impact is that we analyzed the genetic variability in the Asian population and therefore our data present a piece of information from underrepresented populations.