Composición química y actividad AChE-BuChE del aceite esencial de palo santo Bursera graveolens (Kunth) Triana & Planch de Jipijapa, Ecuador / Chemical composition and AChE-BuChE activities of the essential oil of palo santo Bursera graveolens (Kunth) Tr iana & Planch from Jipijapa, Ecuador

Abstract: This article describes the chemical composition, physical properties and acetylcholinesterase (A ChE) and butyrylcholinesterase (BuChE) activity of stem - distilled essential oil (E O ) from Bursera graveolens wood chips, Burseraceae. The plant material was acquired in Quimis (Bosque de Sancán), city of Jipijapa in the province of Manabí, coastal region o f Ecuador. Thirty - six components were identified by CG - MS, which represented 98.54% of the volatile oil. The main components were limonene (68.52%) and mentofuran (20.37%). The hydrocarbon monoterpenes constituted the most abundant fractions. The average y ield of the E O was 1.26%. Regarding the physical properties of E O , the following values were obtained: relative density (1,029 g/mL), refractive index (1,477) and specific rotation (+4,567). The E O presented IC 50 inhibition values of 47.2 and 51.9 µg/mL fo r the enzymes AChE and BuChE, respectively.

Resumen: Este artículo describe la composición química, propiedades físicas y actividad acetilcolinesterasa (AChE) y butirilcolinesterasa (BuChE) del aceite esencial (AE) destilado a vapor de astillas de madera de Bursera graveolens , Burseraceae. La materia vegetal fue adquirida en Quimis (Bosque de Sancán), ciudad de Jipijapa en la provincia de Manabí, región costera d e Ecuador. Treinta y seis componentes fueron identificados por CG - MS, que representaron al 98.54 % del aceite volátil. Los componentes principales fueron limoneno (68.52%) y mentofurano (20.37%). Los monoterpenos hidrocarburos constituyeron las fracciones m ás abundantes. El rendimiento medio del AE fue de 1.26%. Con respecto a las propiedades físicas del AE se obtuvo los siguientes valores, densidad relativa (1.029 g/mL), índice de refracción (1.477) y rotación específica (+4.567). El AE presentó valores de inhibición IC 50 de 47.2 y 51.9 µg/mL para las enzimas AChE y BuChE, respectivamente.

Chemical profile, acetylcholinesterase, butyrylcholinesterase, and prolyl oligopeptidase inhibitory activity of Glaucium corniculatum subsp. refractum

Abstract Papaveraceae is one of the prominent alkaloid-containing families, and plants of the genus Glaucium (Papaveraceae) are known for their bioactive alkaloids. Glaucium species have been used in traditional medicine in Turkey as an analgesic, narcotic, sedative, and antitussive. In this study, it was planned to evaluate the inhibitory activity of an alkaloidal extract of Glaucium corniculatum subsp. refractum on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and prolyl oligopeptidase (POP), as well as exploring the chemical profile of the plant by using Gas Chromatography-Mass Spectrometry (GC-MS). The AChE, BuChE and POP inhibition activities of the alkaloidal extract of G. corniculatum subsp. refractum were determined spectrophotometrically. A rapid GC-MS method was used to identify alkaloids that could be responsible for these inhibition activities. In total, eleven alkaloids were identified in the alkaloid extract of the plant by GC-MS. Allocyptopine (52.92%) and protopine (25.38%) were found as the major constituents. The alkaloidal extract of G. corniculatum subsp. refractum showed potent AChE inhibitory activity (IC50:1.25 µg/mL) and BuChE inhibitory activity (IC50: 7.02 µg/mL). The extract also showed a remarkable inhibitory effect on POP with an IC50 value of 123.69 µg/mL. This study presents the first GC-MS investigation and POP inhibitory activity of G. corniculatum subsp. refractum.

Anticholinesterase activity of ß-carboline-1, 3, 5-triazine hybrids

Abstract The ß-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-ß-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine

Ocotea daphnifolia: phytochemical investigation, in vitro dual cholinesterase inhibition, and molecular docking studies

This study aimed to evaluate the anticholinesterase activities of extracts and fractions of Ocotea daphnifolia in vitro and characterize its constituents. The effects of hexane, ethyl acetate, and ethanolic extracts on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity were determined with a spectrophotometry assay. All extracts inhibited cholinesterase activity, and the ethanolic extract (2 mg/mL) exhibited the highest inhibition of both enzymes (99.7% for BuChE and 82.4% for AChE). The ethanolic extract was fractionated by column chromatography resulting in 14 fractions that were also screened for their anticholinesterase effects. Fraction 9 (2 mg/mL) showed the highest activity, inhibiting AChE and BuChE by 71.8% and 90.2%, respectively. This fraction was analyzed by high-performance liquid chromatography high-resolution mass spectrometry which allowed the characterization of seven glycosylated flavonoids (containing kaempferol and quercetin nucleus) and one alkaloid (reticuline). In order to better understand the enzyme-inhibitor interaction of the reticuline toward cholinesterase, molecular modeling studies were performed. Reticuline targeted the catalytic activity site of the enzymes. Ocotea daphnifolia exhibits a dual cholinesterase inhibitory activity and displays the same pattern of intermolecular interactions as described in the literature. The alkaloid reticuline can be considered as an important bioactive constituent of this plant.

Influence of galantamine in the inflammatory process and tissular lesions caused by Trypanosoma cruzi QM2 strain

Abstract INTRODUCTION: Trypanosoma cruzi infection triggers an inflammatory process with exacerbated production of cytokines that stimulate inflammatory and anti-inflammatory signals, including the efferent anti-inflammatory signal known as the anti-inflammatory cholinergic pathway. Thus, the use of anticholinesterase drugs, such as galantamine, could minimize the inflammatory process caused by this disease. METHODS For the study at 30, 60, and 90 days, 120 Swiss mice were divided into three groups. Each group was subdivided into four subgroups: uninfected/untreated (CTRL), uninfected/treated (GAL), infected/untreated (INF), and infected/treated (GAL/INF). The infected groups were inoculated intraperitoneally with 0.1 ml of mouse blood containing 5 × 104 trypomastigote forms of the T. cruzi QM2 strain. The galantamine-treated groups received 5 mg/kg of galantamine orally, through pipetting. From each subgroup, the parameters of parasitemia, histopathological analysis, butyrylcholinesterase activity (BuChE), and functional study of the colon were evaluated. RESULTS: BuChE performance was observed when AChE was suppressed, with increased activity in the GAL/INF group similar to the INF group on the 30th day post infection, thus corroborating the absence of a significant difference in parasitic curves and histopathological analysis. CONCLUSIONS: The presence of an inflammatory process and nests of amastigotes, as well as evidence of reactivity to ACh and NOR, suggest that galantamine did not interfere with the colonic inflammatory response or even in colonic tissue parasitism at this stage of Chagas disease.

In vitro screening for acetylcholinesterase and butyrylcholinesterase inhibition and antimicrobial activity of chia seeds (Salvia hispanica)

BACKGROUND: Chia seeds are gaining increasing interest among food producers and consumers because of their prohealth properties. RESULTS: The aim of this work was to evaluate the potential of chia seeds to act as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The highest inhibitory activity against AChE and BChE was observed for colored seed ethanol extracts. A positive correlation was found between the presence of quercetin and isoquercetin as well as protocatechuic, hydroxybenzoic, and coumaric acids and the activity of extracts as AChE and BChE inhibitors. It has also been shown that grain fragmentation affects the increase in the activity of seeds against cholinesterases (ChE). Furthermore, seeds have been shown to be a source of substances that inhibit microbial growth. CONCLUSIONS: It was found that the chia seed extracts are rich in polyphenols and inhibit the activity of ChEs; therefore, their use can be considered in further research in the field of treatment and prevention of neurodegenerative diseases.

Investigation of polysaccharide extracts from Iranian and French strains of Agaricus subrufescens against enzymes involved in Alzheimer's disease / Investigación de extractos de polisacáridos de cepas iraníes y francesas de Agaricus subrufescens contra enzimas relevantes para la enfermedad de Alzheimer

In this work, the inhibitory activity of a wide range of polysaccharide extracts from two Iranian and French strains of Agaricus subrufescens were evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, two extracts S9 and S'7 obtained from Iranian and French strains under different extraction conditions showed selective AChE inhibitory activity with IC50 values of 154.63 and 145.43 µg/mL, respectively. It should be noted that all extracts from both strains demonstrated no BChE inhibitory activity. S9 and S'7 were also tested for their effect on amyloid beta (Aß) aggregation, antioxidant activity, and neuroprotectivity. Their activity against Aß aggregation was comparable to that of donepezil as the reference drug but they induced moderate antioxidant activity by DPPH radical scavenging activity and negligible neuroprotectivity against Aß-induced damage.

En este trabajo, se evaluó la actividad inhibitoria de acetilcolinesterasa (AChE) y butirilcolinesterasa (BChE) para varios extractos de polisacáridos de dos cepas iraníes y francesas de Agaricus subrufescens. Los extractos más potentes mostraron valores de IC50 de 154,63 y 145 µg/ml para las cepas iraní (S9) y francesa (S'7), respectivamente, las cuales se obtuvieron de diferentes condiciones de extracción; sin embargo, todos los extractos no mostraron actividad inhibitoria de BChE. Además, S9 y S'7 se probaron para determinar su efecto sobre la agregación de beta-amiloide (Aß), así como su actividad antioxidante y neuroprotectora. Su actividad inhibitoria de la agregación de Aß fue comparable con donepezil, fármaco de referencia, pero indujeron una actividad antioxidante moderada, medida mediante la captación de radicales DPPH, y una neuroprotectora insignificante contra el daño inducido por Aß.

Chemical Constituents from Solenostemma argel and their Cholinesterase Inhibitory Activity

Alzheimer's disease is a chronic neurodegenerative disorder with no curative treatment. The commercially available drugs, which target acetylcholinesterase, are not satisfactory. The aim of this study was to investigate the cholinesterase inhibitory activity of Solenostemma argel aerial part. Eight compounds were isolated and identified by NMR: kaempferol-3-O-glucopyranoside (1), kaempferol (2), kaempferol-3-glucopyranosyl(1→6)rhamnopyranose (3) p-hydroxybenzoic acid (4), dehydrovomifoliol (5), 14,15-dihydroxypregn-4-ene-3,20-dione (6), 14,15-dihydroxy-pregn-4-ene-3,20-dione-15β-D-glucopyranoside (7) and solargin I (8). Two of them (compounds 2 and 3) could inhibit over 50 % of butyrylcholinesterase activity at 100 µM. Compound (2) displayed the highest inhibitory effect against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with a slight selectivity towards the latter. Molecular docking studies supported the in vitro results and revealed that (2) had made several hydrogen and π-π stacking interactions which could explain the compound potency to inhibit AChE and BChE.

Deficiencia de butirilcolinesterasa identificada después de la administración de succinilcolina. Reporte del caso / Butyrylcholinesterase deficiency identified after succinylcholine administration. Case report

RESUMEN La función principal de la enzima butirilcolinesterasa es hidrolizar ésteres exógenos como los que están presentes en el relajante neuromuscular succinilcolina, que se utiliza con frecuencia en procedimientos quirúrgicos de corta duración. Se considera que la herencia de butirilcolinesterasa atípica o deficiencia de butirilcolinesterasa es un rasgo autosómico recesivo que se presenta aproximadamente en una de cada 3200 a 5000 personas. Dicha deficiencia puede tener consecuencias graves en pacientes anestesiados con dicho relajante porque en ocasiones causa prolongación de la parálisis o apnea posoperatoria. Se presenta el caso de una paciente de 73 años admitida al servicio de cirugía para una tiroidectomía subtotal. Finalizada la intervención, no emergió espontáneamente del anestésico, presentó signos de relajación con mal esfuerzo inspiratorio y sin recuperar la respuesta neuromuscular; por ello se procedió a revertir con neostigmina, previa aplicación de atropina. La reversión falló por lo que fue trasladada a la unidad de cuidados intensivos. En los exámenes se halló reducido el nivel de colinesterasa sérica, lo que indicó una deficiencia de butirilcolinesterasa compatible con sus síntomas. Tal situación está descrita en la literatura médica.

SUMMARY The main function of the enzyme butyrylcholinesterase is to hydrolyze exogenous esters such as those present in the neuromuscular blocking agent succinylcholine, which is frequently used in short surgical procedures. Inheritance of atypical butyrylcholinesterase or butyrylcholinesterase deficiency is considered an autosomal recessive characteristic and occurs worldwide in approximately one out of 3200 to 5000 people. Such deficiency may have serious consequences for patients anesthetized with that relaxant because sometimes it causes an extension of paralysis or postoperative apnea. We report the case of a 73-year-old woman submitted to subtotal thyroidectomy. After surgery, she did not spontaneously emerge from anesthesia, had signs of relaxation with poor inspiratory effort, and no recovery of neuromuscular response. After application of atropine, reversal was attempted with neostigmine, but it failed, and she was transferred to the ICU. Laboratory results revealed a reduced level of serum cholinesterase indicating a deficiency in butyrylcholinesterase consistent with her symptoms. Such situation has been described in medical literature.

Relative Risk and Clinical Severity Assessment in Patients with Non-Oral Route Organophosphate Poisoning Compared with Oral Route Poisoning

PURPOSE: Organophosphates, commonly used in agricultural pesticides, pose high risks and incidences of poisoning. In the present study, we investigated the relative risk and clinical severity, including laboratory results, of non-oral route poisoning (NORP) patients, compared to oral route poisoning (ORP) patients. MATERIALS AND METHODS: A single institutional toxicology database registry was utilized to gain information on clinical laboratory results on organophosphate poisoning patients who visited the emergency department (ED) between January 2000 and October 2016. Clinical outcomes, such as mortality and complication rates, were compared using 1:2 propensity score matching in the total cohort. RESULTS: Among a total of 273 patients in our study, 34 experienced NORP. After 1:2 propensity score matching, rates of respiratory complications and mortality were higher in the ORP group than in the NORP group. However, there was no difference in hospitalization time and time spent in the intensive care unit between the two groups. Compared with ORP patients after matching, the relative risk of mortality in NORP patients was 0.34, and the risk of respiratory distress was 0.47. The mean level of pseudocholinesterase was significantly higher in the NORP group than in the ORP group, while recovery rates were similar between the two groups. CONCLUSION: Although the majority of NORP patients were admitted to the ED with unintentional poisoning and the relative risk of NORP was lower than that for ORP, we concluded that NORP is as critical as ORP. Considerable medical observation and intensive therapeutic approaches are also needed for NORP patients.

Isolation of Flavonoid Glycosides with Cholinesterase Inhibition Activity and Quantification from Stachys japonica

The three flavone glycosides, 4′-O-methylisoscutellarein 7-O-(6‴-O-acetyl)-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (1), isoscutellarein 7-O-(6‴-O-acetyl)-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (3), and isoscutellarein 7-O-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (4) in addition to a flavonol glycoside, kaempferol 3-O-β-D-glucopyranoside (astragalin, 2), were isolated from Stachys japonica (Lamiaceae). In cholinesterase inhibition assay, compound 1 significantly inhibited aceylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (IC₅₀s, 39.94 µg/ml for AChE and 86.98 µg/ml for BChE). The content of isolated compounds were evaluated in this plant extract by HPLC analysis. Our experimental results suggest that the flavonoid glycosides of S. japonica could prevent the memory impairment of Alzheimer's disease.

Garcinexanthone G, a Selective Butyrylcholinesterase Inhibitor from the Stem Bark of Garcinia atroviridis

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor (12.65 ± 1.57 µg/ml) while garcinexanthone G (6) was the most active BChE inhibitor (18.86 ± 2.41 µg/ml). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.

Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study

Objective Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. Subjects and methods One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. Results The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. Conclusion In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.

Actividad de butirilcolinesterasa y micronúcleos en trabajadores agrícolas expuestos a mezclas de plaguicidas / Butyrylcholinesterase activity and micronuclei in agricultural workers exposed to pesticide mixtures

Los plaguicidas son xenobióticos de gran utilidad para el control de las plagas y su uso es una realidad para obtener mayor rendimiento en los cultivos. Sin embargo, tienen el riesgo de producir toxicidad, por lo que es necesario el monitoreo biológico de los trabajadores expuestos a estas sustancias. El objetivo de este estudio fue evaluar la actividad de la butirilcolinesterasa (BCh) y la presencia de micronúcleos (MN) en trabajadores expuestos a mezclas de plaguicidas en el municipio Urdaneta, estado Lara. Participaron 82 individuos de sexo masculino, 41 expuestos (GE) y 41 no expuestos (GNE), la determinación de la butirilcolinesterasa se realizó en muestras de sangre, y la de micronúcleos en muestras epiteliales de la mucosa bucal. Los resultados fueron presentados empleando estadísticos descriptivos, frecuencias absolutas y porcentajes, utilizando el paquete libre PAST v.2.04. Los valores de actividad de BCh en el GE (3528,75+/- 1162,45U/L) mostraron diferencias estadísticamente significativas (P<0,001) en relación al GNE (5764,41+/-1641,43U/L). La frecuencia de MN presentó mayor mediana en el GE respecto al GNE (3,09 vs 0,73) con una diferencia significativa (P<0,001). Al asociar el tiempo de exposición con la actividad de BCh y la frecuencia de MN, se presentó una correlación negativa con la actividad de BCh y una correlación positiva con los MN, estadísticamente significativas P<0,001 y P<0,05. Los hallazgos obtenidos reflejan que los plaguicidas fueron utilizados en forma de mezclas siendo los más usados: organofosforados, carbamatos y piretroides produciendo modificaciones en los valores de actividad de BCh y la frecuencia de MN en individuos expuestos a plaguicidas(AU)

Pesticides are xenobiotics, useful in controlling pests and their use ileads to greater crop yields. However, they carry a risk of toxicity so biological monitoring of exposed workers is necessary. The aim of this study was to evaluate the cholinesterase activity and the presence of micronuclei in workers exposed to pesticide mixtures in the town of Urdaneta, Lara. Eighty-two workers participated, 41 exposed (EG) and 41 nonexposed (NEG), all of whome were male. Blood samples were obtained for the determination of butyrylcholinesterase (BCh); buccal mucosal epithelial samples were obtained for micronuclei (MN) sampline. The results were presented as descriptive statistics, absolute frequencies and percentages, using the PAST v.2.04 a free online software package. The BCh activity values in the EG (3528.75+/-1162.45U/L) showed statistically significant differences (P<0.001) in relation to the UEG (5764.41 +/- 1641.43U/L). Median MN frequency was highest in the EG compared to UEG (3.09vs 0.73), a significant difference (P<0.001). By associating exposure time with BCh activity and MN frequency, a negative correlation was found with BCh activity and a positive correlation with MN, both statistically significant (P<0.001 and P<0.05, respectively). The results suggested pesticide mixtures were the most often used: organophosphates, carbamates and pyrethroids produced changes in the activity values of BCh and the frequency of MN in individuals exposed to pesticides(AU)

Sesquiterpenoids from the heartwood of Juniperu s chinensis

A new sesquiterpenoid, 11-hydroxy-valenc-1(10),3(4)-dien-2-one (3), two chemically synthesized but first isolate from nature, 3-oxocedran-8β-ol (1) and valenc-1(10),3(4),11(12)-trien-2-one (2) along with four known compounds, sugiol (4), (+)-nootkatone (5), 11-hydroxy-valenc-1(10)-en-2-one (6), and clovandiol (7), were isolated from the heartwood of Juniperus chinensis. All chemical structures were elucidated using extensive spectroscopic analysis including 1D and 2D NMR spectroscopy. Valenc-1(10),3(4),11(12)-trien-2-one (2) exhibited significant inhibitory activity against butyrylcholinesterase with an IC₅₀ value of 68.45 µM.

Biomarcadores inflamatórios e de estresse oxidativo em cadelas submetidas à ovário-histerectomia videoassistida ou convencional / Inflammation and oxidative stress indicators in bitches submitted to laparoscopic-assisted or conventional ovariohysterectomy

A videocirurgia é atualmente uma das principais ferramentas operatórias, com vantagens que incluem menor estresse, incisões e dor pós-operatória quando comparada aos procedimentos abertos. Objetivou-se comparar o processo inflamatório e o estresse oxidativo resultantes das técnicas de ovário-histerectomia (OVH) convencional e videoassistida, com dois portais em cadelas, por meio de hemograma, avaliação de acetilcolinesterase, butirilcolinesterase, catalase e malondialdeído séricos, imediatamente antes da operação e duas, seis, 12, 24, 48 e 72 horas após a cirurgia. Observou-se menor estresse cirúrgico nas pacientes operadas pela técnica videoassistida, e sugere-se que a técnica convencional possa implicar peroxidação lipídica, mesmo com o uso de anti-inflamatório.(AU)

Videosurgery is currently a very important surgical tool with several benefits over the open surgery, including less surgical stress, shorter incisions and less postoperative pain. The purpose of this study was to compare the inflammatory process and oxidative stress between conventional and two-port laparoscopic-assisted ovariohisterectomy (OVH) in bitches. Complete blood counting, serum acetylcholinesterase, butyrylcholinesterase, catalase and malondialdehyde were assessed on the baseline and at two, six, 12, 24, 48 and 72 hours after surgery. The patients submitted to the videoassisted technique presented lower inflammatory response. There are suggestions that the conventional technique promotes lipid peroxidation, even with the use of anti-inflammatories.(AU)

Evaluation of Antioxidant, Anti-cholinesterase, and Anti-inflammatory Effects of Culinary Mushroom Pleurotus pulmonarius

Culinary mushroom Pleurotus pulmonarius has been popular in Asian countries. In this study, the anti-oxidant, cholinesterase, and inflammation inhibitory activities of methanol extract (ME) of fruiting bodies of P. pulmonarius were evaluted. The 1,1-diphenyl-2-picryl-hydrazy free radical scavenging activity of ME at 2.0 mg/mL was comparable to that of butylated hydroxytoluene, the standard reference. The ME exhibited significantly higher hydroxyl radical scavenging activity than butylated hydroxytoluene. ME showed slightly lower but moderate inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase than galantamine, a standard AChE inhibitor. It also exhibited protective effect against cytotoxicity to PC-12 cells induced by glutamate (10~100 µg/mL), inhibitory effect on nitric oxide (NO) production and inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, and carrageenan-induced paw edema in a rat model. High-performance liquid chromatography analysis revealed the ME of P. pulmonarius contained at least 10 phenolic compounds and some of them were identified by the comparison with known standard phenolics. Taken together, our results demonstrate that fruiting bodies of P. pulmonarius possess antioxidant, anti-cholinesterase, and inflammation inhibitory activities.

Convergent synthesis of new N -substituted 2-{[5-(1H -indol-3-ylmethyl)-1, 3, 4-oxadiazol-2-yl]sulfanyl}acetamides as suitable therapeutic agents

abstract A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl)acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents.

resumo Uma série de acetamidas 2-{[5-(1H-indol-3-ilmetil)-1,3,4-oxadiazol-2-il]sulfanila} N-substituídas (8a-w) foi sintetizada em três fases. A primeira etapa envolveu a conversão sequencial de ácido 2-(1H-indol-3-il)acético (1) a éster (2), seguido por hidrazida (3) e, finalmente, a e ciclização na presença de CS2 e KOH alcoólico produziu 5-(1H-indol-3-il- metil)-1,3,4-oxadiazole-2-tiol (4). Na segunda etapa, aminas arílicas/aralquílicas(5a-w) reagiram com brometo de 2-bromoacetila (6​​), em meio básico, para se obter acetamidas 2-bromo-N-substituídas (7a-w). Na terceira etapa, estes eletrófilos (7a- w) reagiram com 4, para se obter os compostos alvo (8a-w). A elucidação estrutural de todos os derivados sintetizados foi realizada por 1H-NMR, IR e técnicas de espectrometria de EI-MS. Além disso, eles foram submetidos a triagem de atividade antibacteriana e hemolítica. Análise da inibição enzimática foi bem apoiada pelos resultados de docking molecular. Por exemplo, o composto 8q exibiu melhor potencial inibitório contra α-glicosidase, e os compostos 8g e 8b exibiram, comparativamente, melhor inibição contra butirilcolinesterase (BChE) elipoxigenase (LOX), respectivamente. Do mesmo modo os compostos 8b e 8c mostraram excelente potencial antibacteriano contra SalmonellaTyphi, semelhante ao do ciprofloxacino, antibiótico padrão usado neste estudo. Os compostos 8c e 8l também mostraram excelente potencial antibacteriano contra Staphylococcus aureus . Quase todos os compostos mostraram pequena atividade hemolítica, sendo que o composto 8p apresentou menor atividade. Assim, as moléculas sintetizadas podem ter a sua utilidade como agentes terapêuticos adequados.

Laboratory genetic-based reference values for cholinesterase activity in a Colombian population: A step forward in personalized diagnostics / Valores de referencia basados en el contexto genético de la actividad enzimática de la colinesterasa en una población colombiana: un paso hacia el diagnóstico personalizado

Introduction: The determination of cholinesterase (ChE) activity has been commonly applied in the biomonitoring of exposure to organophosphate and carbamate pesticides. However, ChE activity is influenced by genetic factors. Integrating genotype and phenotype information in clinical laboratory tests would increase the accuracy of the reference values in well-defined populations. Objective: To establish genetic-based reference values for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in a Colombian population. Materials and methods: A total of 397 healthy adults from Bucaramanga were included in the study. AChE and BChE activities were measured in blood samples by potentiometry and spectrophotometry, respectively. Genotyping for ACHE rs17880573 and BCHE rs1803274 was performed using the TaqMan allelic discrimination assay. The statistical analyses to obtain the reference values were performed with the MedCalc® software. Results: Allele frequencies were 10.58% for rs17880573 A and 8.82% for rs1803274 A. People with genotypes rs1803274 AA and AG showed a reduction of 20.69% and 10.92% respectively in mean BChE activity compared to people with genotype GG. No significant differences were identified in AChE activity between rs17880573 alleles or genotypes. In the overall sample, the corresponding reference values were as follows: for AChE activity, 0.62-0.98 D pH/h and for BChE activity, 4796.3-10321.1 U/L for people carrying the allele rs1803274A and 5768.2-11180.4 U/L for people carrying the genotype rs1803274 GG. Conclusion: We strongly recommend using these genetic-based reference values for ChE enzymes in our well-defined population in daily clinical practice.

Introducción. La determinación de la actividad enzimática de la colinesterasa se utiliza comúnmente en la vigilancia biológica de la exposición a pesticidas organofosforados y carbamatos. Sin embargo, los factores genéticos afectan la actividad de la colinesterasa, por lo que la integración de la información sobre genotipos y fenotipos en las pruebas de laboratorio clínico, incrementaría la precisión de los valores de referencia. Objetivo. Establecer los valores de referencia basados en el contexto genético para la actividad enzimática de la acetilcolinesterasa (AChE) y la butirilcolinesterasa (BChE), en una población colombiana. Materiales y métodos. Se incluyeron 397 adultos sanos. La actividad de la acetilcolinesterasa y la de la butirilcolinesterasa, se determinaron en muestras de sangre por potenciometría y espectrofotometría, respectivamente. Los genotipos de los ACHE rs17880573 y BCHE rs1803274 se obtuvieron mediante el ensayo TaqMan y los valores de referencia se estimaron con el programa MedCalc®. Resultados. La frecuencia alélica fue de 10,58 % para rs17880573 A y de 8,82 % para rs1803274 A. Las personas con los genotipos rs1803274 AA y AG, mostraron una reducción en el promedio de la actividad de la butirilcolinesterasa de 20,69 % y de 10,92 %, respectivamente, comparados con aquellas con el genotipo GG. No se encontraron diferencias significativas en la actividad de la acetilcolinesterasa con respecto a los alelos y genotipos del rs17880573. Los valores de referencia determinados para esta población fueron de 0,62-0,98 D pH/h para acetilcolinesterasa y de 4796,3-10321,1 U/L para butirilcolinesterasa, en las personas portadoras del alelo rs1803274 A, y de 5768,2-11180,4 U/L, en las portadoras del genotipo rs1803274 GG. Conclusión. Se recomienda el uso de estos valores de referencia basados en el contexto genético para las colinesterasas, en la práctica clínica diaria en esta población.

Failed reversal of neuromuscular blockade despite sugammadex: a case of undiagnosed pseudocholinesterase deficiency

The management of an undetected pseudocholinesterase deficiency in a parturient who underwent urgent cesarean section has been presented. After rapid sequence induction with succinylcholine, rocuronium was used for maintenance of neuromuscular block. At the end of the operation neostigmine was given to antagonize the residual block. Upon persistent prolonged neuromuscular blockade sugammadex was administered. Probable reasons, drug interactions, the importance of suspecting pseudocholinesterase deficiency and the need of neuromuscular monitoring have been argued in this case report