Protective effect of huperzine A on phenytoin induced cognition impairment: Behavioral and biochemical study

Phenytoin, a drug of choice for Epilepsy is also known for its adverse effects. The most common adverse effect due to phenytoin is cognition impairment. Cognition impairment is a serious problem in society as it debars the person's social life. Thus to overcome such a problem demand for a solution arises. Huperzine, sesquiterpene alkaloids having immense neuroprotective properties. Thus in this study, it was aimed to evaluate the effectiveness of huperzine on Phenytoin- induced Cognition Impairment. The protective effect of huperzine on phenytoin-induced cognition impairment was evaluated in rats. The effect of Huperzine on phenytoin-induced cognitive impairment was evaluated by behavioral, biochemical, and histopathological studies. The co-administration of huperzine with phenytoin showed significant results. The treatment of Huperzine with phenytoin resulted in significant improvement in learning and memory. The oxidative stress induced by Phenytoin was reversed by huperzine. A significant decrease in cholinesterase activity was also observed. The histopathology showed damaged neuronal cells in periventricular regions and cortex due to phenytoin which was altered by Huperzine. Thus, the present study demonstrates the protective effect of huperzine on phenytoin-induced cognition impairment.

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.

Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in women

Abstract Butyrylcholinesterase (BChE) activity and polymorphisms in its encoding gene had previously been associated with metabolic traits of obesity. This study investigated the association of three single nucleotide polymorphisms (SNPs) in the BCHE gene: -116G > A (rs1126680), 1615GA (rs1803274), 1914A < G (rs3495), with obesity and lipid metabolism markers, body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG) levels, and BChE enzymatic activity in obese (BMI≥30/n = 226) and non-obese women (BMI < 25/n = 81). BCHE SNPs genotyping was obtained by TaqMan allelic discrimination assay and by RFLP-PCR. Plasmatic BChE activity was measured using propionylthiocholine as substrate. Similar allele frequencies were found in obese and non-obese women for the three studied SNPs (p > 0.05). The dominant and recessive models were tested, and different effects were found. The -116A allele showed a dominant effect in BChE activity reduction in both non-obese and obese women (p = 0.045 and p < 0.001, respectively). The 1914A > G and 1615GA SNPs influenced the TG levels only in obese women. The 1914G and the 1615A alleles were associated with decreased plasma levels of TG. Thus, our results suggest that the obesity condition, characterized by loss of energy homeostasis, is modulated by BCHE polymorphisms.

Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential.

A doença de Alzheimer (DA) é uma doença neurodegenerativado sistema nervoso central, em rápido crescimento, e antioxidantes ajudam a suprimir o estresse oxidativo causado por radicais livres, responsávies pela DA. Avaliou-se, biologicamente, série de derivados sintéticos de indol selecionados para identificar novos antioxidantes. A maioria dos compostos avaliados apresentou de significativa a boa propriedade antioxidante (valor de IC50 399,07140.0 ± 50 µM). Eftuaram-se estudos de Teoria do Funcional de Densidade (DFT) com os compostos e os seus correspondentes radicais livres. As diferenças de energia entre os compostos protótipos e os radicais livres correspondentes proporcionaram boa justificativa para a tendência encontrada nos seus valores de IC50. O ancoramento in silico dos compostos com a acetilcolinesterase (AChE) e com a butirilcolinesterase (BChE), que contribuem para a DA, foi, também, realizado para prever o seu potencial anti-DA.

Atividade da butirilcolinesterase e fatores de risco cardiovascular em adolescentes obesos submetidos a um programa de exercícios físicos / Butyrylcholinesterase activity and cardiovascular risk factors in obese adolescents submitted to an exercise program

OBJETIVO: Avaliar o efeito de 12 semanas de exercícios físicos em variáveis associadas a fatores de risco cardiovascular e na atividade da butirilcolinesterase (BChE) em adolescentes obesos. SUJEITOS E MÉTODOS: A amostra foi composta por 24 obesos e 51 eutróficos controles. Inicialmente e após 12 semanas foram avaliados: peso, estatura, IMC, circunferência abdominal (CA), percentual de gordura (%G), consumo máximo de oxigênio (VO2máx), pressão arterial sistólica (PAS) e diastólica (PAD), glicemia (GLI) e insulinemia (INS) basal e após 120 min, triacilglicerol (TG), colesterol total (CT), colesterol LDL, colesterol HDL e a atividade da BChE (kU/l). RESULTADOS: Após a intervenção, houve redução significativa no IMC, CA, %G, PAD, PAD, TG, GLI 120, INS, INS 120 min e na atividade da BChE. CONCLUSÃO: A redução da atividade da BChE, observada após a intervenção, foi acompanhada da redução de variáveis associadas a risco cardiovascular e à obesidade, indicando que a BChE pode ser utilizada como marcador secundário para os riscos associados à obesidade precoce.

OBJECTIVE: To evaluate the effect of 12 weeks of physical exercise (PE) on cardiovascular risk factors and BChE activity in obese adolescents. SUBJECTS AND METHODS: The sample consisted of 24 obese adolescents and 51 normal weight controls. The following variables were measured in the initial stage and after 12 weeks: weight, height, BMI, waist circumference (WC), fat percentage (% F), maximal oxygen uptake (VO2max), systolic (SBP) and diastolic (DBP) blood pressure, glucose (GLY) and insulin (INS) at baseline and after 120 min, triacylglycerol (TG), total cholesterol (TC), LDL cholesterol, HDL cholesterol, and BChE activity (kU/l). RESULTS: After the intervention, there was significant reduction in BMI, WC, %F, TG, GLI 120, INS 120 min, and BChE activity. CONCLUSION: The reduction in BChE activity, observed after physical exercise, was accompanied by the reduction of the variables associated with cardiovascular risk and obesity, indicating that BChE can be used as a secondary marker for the risk associated with early onset obesity.

Influence of Toxoplasma gondii Acute Infection on Cholinesterase Activities of Wistar Rats

Several studies have shown the mechanisms and importance of immune responses against Toxoplasma gondii infection and the notable role of cholinesterases in inflammatory reactions. However, the association between those factors has not yet been investigated. Therefore, the aim of this study was to evaluate the acetylcholinesterase (AChE) activity in blood and lymphocytes and the activity of butyrylcholinesterase (BChE) in serum of rats experimentally infected with T. gondii during the acute phase of infection. For that, an in vivo study was performed with evaluations of AChE and BChE activities on days 5 and 10 post-infection (PI). The activity of AChE in blood was increased on day 5 PI, while in lymphocytes its activity was enhanced on days 5 and 10 PI (P<0.05). No significant difference was observed between groups regarding to the activity of BChE in serum. A positive (P<0.01) correlation was observed between AChE activity and number of lymphocytes. The role of AChE as an inflammatory marker is well known in different pathologies; thus, our results lead to the hypothesis that AChE has an important role in modulation of early immune responses against T. gondii infection.

Evaluation of the Antioxidant and Anti-Cholineesterase activities of the Stem, Barks and Leaves of the Plant Vernonia Cinerea (Family: Asteraceae).

The aim of this study was to evaluate the anti-oxidant and anti-choline esterase activity of the stem, barks and leaves of the plant V. cinerea. The stems, barks and the leaves of the plant V.Cineria was sun dried and extracted using methanol. The anti-oxidant activity of the crude methanolic extract was measured by the DPPH free radical scavenging activity. The crude methanolic extract showed significant anti-oxidant activity by the DPPH free radical scavenging method. Evaluation of ChEs enzyme activity of the crude methanolic extract was done by Ellman method. The methanolic extract of V. cinerea leaves exerted significant AChE and BChE inhibitory effects.

Baseline plasmaccholinesterase activities in argentine saddle horses from sabana deboogotá / Activdad colinessterasa plasmática en caballos silla Argentina de la sabana de bogotá

The determination of cholinesterase (ChE) activity in domestic animals is of great importance for diagnosis and research purposes. The present work was aimed to determine the baseline plasma ChE activities (acetylcholinesterase, AChE and butyrylcholinestarase, BChE) of Argentine saddle horses sampled from equine farms of Bogota (Colombia) and its surroundings. Plasma AChE and BChE catalytic activities were measured in 60 healthy horses by spectrophotometry within the visible spectrum (405 nm). AChE mean ± SD values (nmols/ml/min) for males (n=32) were 1566 ± 301. Age intervals results were, 0.5-5 years: 1526 ± 295, 6-10 years: 1532 ± 313, 11-15 years: 1615 ± 279, and > 15 years: 1617 ± 335. As for females (n=28), mean AChE was 1323 ± 432, with age intervals as follows, 0.5-5 years: 719 ± 108, 6-10 years: 1603 ± 313, 11-15 years: 1225 ± 294, > 15 years: 1519 ± 369. BChE in males were 3304 ± 822; with age intervals, 0.5-5 years: 3383 ± 715, 6-10 years: 3360 ± 766, 11-15 years: 3267 ± 1064, > 15 years: 3206 ± 861. As for females, BChE values were 3097 ± 432, with age intervals: 0.5-5 years: 2467 ± 981, 6-10 years: 3668 ± 750, 11-15 years: 3238 ± 979, and > 15 years: 3015 ± 925. AChE was significantly different between males and females (t test, p < 0.05) and for both genders when age groups were compared (ANOVA, p < 0.05). BChE had higher values than AChE for both genders and yet no significant difference was found when genders were compared. No differences were found in BChE for age groups in both genders. In a second test, 15 random samples, kept at 4 ºC for 72 hours, were analyzed for variations when measured every 24h. Neither AChE nor BChE had significant variations in these 24h-apart measurements. The present investigation found baseline activities for the two types of plasma cholinesterases in Argentinian saddle horses. This will allow researchers and clinicians to count on reference values for diagnosis and comparative purposes.

La determinación de la actividad colinesterasa (ChE) en animales domésticos es de importancia en diagnóstico e investigación. El presente trabajo tuvo como objetivo principal la determinación de la línea base de actividad ChE plasmática (acetilcolinesterasa, AChE y butirilcolinesterasa, BChE) en 60 caballos Silla Argentino muestreados en fincas de equinos ubicadas en Bogotá (Colombia) y sus alrededores. Las actividades catalíticas de AChE y BChE plasmáticas fueron medidas mediante espectrofotometría visible (405 nm). Los valores promedio ± desviación estándar de actividad AChE (nmols/ml/ min) para machos (n=32) fueron 1566 ± 301. En intervalos de edad, los resultados fueron, 0.5-5 años: 1526 ± 295, 6-10 años: 1532 ± 313, 11-15 años: 1615 ± 279, y > 15 años: 1617 ± 335. En hembras (n=28), la actividad AChE fue 1323 ± 432, con valores en intervalos de edad, 0.5-5 años: 719 ± 108, 6-10 años: 1603 ± 313, 11-15 años: 1225 ± 294, > 15 años: 1519 ± 369. La BChE en machos fue 3304 ± 822; con intervalos de edad, 0.5-5 años: 3383 ± 715, 6-10 años: 3360 ± 766, 11-15 años: 3267 ± 1064, > 15 años: 3206 ± 861. En hembras, la BChE fue 3097 ± 432, con intervalos de edad: 0.5-5 años: 2467 ± 981, 6-10 años: 3668 ± 750, 11-15 años: 3238 ± 979, y > 15 años: 3015 ± 925. La actividad AChE fue significativamente diferente entre machos y hembras (test t, p < 0.05) y en ambos géneros al comparar los grupos etáreos (ANAVA, p < 0.05). BChE tuvo valores más altos que AChE, sin embargo, no en forma significativa cuando se compararon los resultados entre los dos géneros, ni cuando se compararon los grupos etáreos en los dos géneros. En una prueba adicional, 15 muestras fueron tomadas al azar y mantenidas a 4ºC durante 72 horas para ser analizadas cada 24 horas; AChE y BChE no mostraron variaciones significativas entre las mediciones hechas en este período de tiempo. El presente estudio permitió determinar lineas base de los dos tipos de colinesterasas plasmáticas en caballos tipo silla Argentino con el propósito de ofrecer valores de referencia con fines diagnósticos y comparativos para clínicos e investigadores.

Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase) genes

Ghrelin coded by the GHRL gene is related to weight-gain, its deactivation possibly depending on its hydrolyzation by butyrylcholinesterase (BChE) encoded by the BCHE gene, an enzyme already associated with the body mass index (BMI). The aim was to search for relationships between SNPs of the GHRL and BCHE genes with BChE activity, BMI and obesity in 144 obese and 153 nonobese Euro-Brazilian male blood donors. In the obese individuals, a significant association with higher BChE activity, in the 72LM+72MM; -116GG genotype class (GHRL and BCHE genes, respectively) was noted. No significant differences were found otherwise, through comparisons between obese and control individuals, of genotype and allele frequencies in SNPs of the GHRL gene (Arg51Gln and Leu72Met), or mean BMI between 72LL and 72LM+72MM genotypes. Although there appears to be no direct relationship between the examined GHRL SNPs and BMI, the association of the 72M SNP with higher BChE activity in obese subjects probably points to a regulatory mechanism, thereby implying the influence of the GHRL gene on BChE expression, and a consequential metabolic role in the complex process of fat utilization.

Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine

Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5'UTR showed that the proband and her brother are homozygous for -116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44 percent). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis.

Butyrylcholinesterase and diabetes mellitus in the CHE2 C5- and CHE2 C5+ phenotypes / Butirilcolinesterase e diabetes melito nos fenótipos CHE2 C5- e CHE2 C5+

OBJECTIVE:To investigate the relationship between butyrylcholinesterase (BChE) activities (total and band specific) and diabetes mellitus. SUBJECTS AND METHODS: BChE activities (BChEA, AC 4/5, AC OF and RC5) were analyzed in 101 type 1 (DM1) and in 145 type 2 (DM2) diabetic patients, in relation to phenotype, weight and incidence of metabolic syndrome (MS) in these patients. The C4/5 and C5 complex were separated from other molecular forms (C OF) using an acid agar gel. RESULTS: The BChE activity (BChEA) and the absolute activities of C4/5 (AC4/5) and C OF (AC OF) showed a high positive correlation coefficient to weight in the CHE2 C5- group, while the relative activity of C5 complex (RC5) showed a negative correlation to weight. CONCLUSIONS: The present study suggests that the positive correlation of the BChE activities to diabetes mellitus and to insulin resistance may depend on the CHE2 locus variability. High values of BChE activities were associated with insulin resistance only in CHE2 C5- diabetic patients, while in CHE2 C5+ diabetic patients, the presence of C5 complex, especially in a relatively high proportion, leads to less fat storage and better protection against metabolic syndrome.

OBJETIVO: Investigar a associação entre as atividades (total e banda específica) da butirilcolinesterase (BChE) e diabetes melito. SUJEITOS E MÉTODOS: As atividades da BChE (BChEA, AC4/5, AC OF e RC5) foram analisadas em 101 pacientes diabéticos do tipo 1 (DM1) e 145 do tipo 2 (DM2) em relação aos fenótipos, ao peso e à incidência da síndrome metabólica. Os complexos C4/5 e C5 foram separados das outras formas moleculares (C OF), usando gel de ágar ácido. RESULTADOS: A atividade da BChE (BChEA) e as atividades absolutas de C4/5 (AC4/5) e de C OF (AC OF) mostraram altos coeficientes de correlações positivos com peso no grupo de CHE2 C5-, enquanto a atividade relativa do complexo C5 (RC5) mostrou correlação negativa com o peso. CONCLUSÕES: O presente estudo sugere que as correlações positivas das atividades da BChE com diabetes melito e com a resistência à insulina podem depender da variabilidade do loco CHE2. Altos valores nas atividades da BChE estão associados com a resistência à insulina somente nos pacientes diabéticos CHE2 C5-, enquanto nos pacientes diabéticos CHE2 C5+ a presença do complexo C5, especialmente em alta proporção relativa, leva a um menor estoque de gordura e à maior proteção contra a síndrome metabólica.

Molecular forms of butyrylcholinesterase and obesity

This study compared obese (N = 134) and unobese (N = 92) male blood donors, regarding the relative intensity (RI) and activity of different molecular forms (G1, G2, G4 and G1-ALB) of butyrylcholinesterase (BChE, EC 3.1.1.8) found in plasma, thereby searching for an association between these variables with obesity and SNPs of exons 1 and 4 of the BCHE gene. It was shown that obese and unobese individuals do not differ in the RI of each BChE band, even when classifying the sample into three genotypes of exons 1 and 4 of the BCHE gene (-116GG/539AA, -116GG/539AT, -116GA/539AT). Although the mean BChE activity of each band was significantly higher in obese than in unobese blood donors, the proportions of BChE bands were maintained, even under the metabolic stress associated to obesity, thereby leading to infer that this proportion is somehow regulated, and may therefore be important for BChE functions.

Absence of the -116A variant of the butyrylcholinesterase BCHE gene in Guarani Amerindians from Mato Grosso do Sul

Butyrylcholinesterase (BChE; EC 3.1.1.8; Online Mendelian Inheritance in Man (OMIM) number 177400) is an enzyme found in many human tissues and encoded by the BCHE gene, of which 65 variants have been identified. In a recent study we found that the -116A variant of exon 1 of the BCHE gene was associated with lower mean BChE activity. The present study analyzed the -116 single nucleotide polymorphism (SNP) in 253 Guarani Amerindian Brazilians from the state of Mato Grosso do Sul (148 Guarani-Kaiowá, 83 Guarani-Ñandeva and 22 Kaiowá-Ñandeva descendants) and verified that they were all homozygotic for the -116G variant. A comparative analysis of the -116 site in nine vertebrate species indicated the -116A variant as the ancestral type. This is the first study of the -116 SNP in Amerindians and it is therefore difficult to infer whether or not the -116A variant was always absent from southern paleo-Amerindians or was present and then subsequently lost due to evolutionary factors.