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.
Acetylcholinesterase ; Alzheimer Disease ; Butyrylcholinesterase ; Cholinesterases ; Hydrogen ; In Vitro Techniques ; Neurodegenerative Diseases

Cholinesterase (ChE) is one of the most ubiquitous enzymes and in addition to its well characterized catalytic function, the morphogenetic involvement of ChE has also been demonstrated in neuronal tissues and in non-neuronal tissues such as bone and cartilage. We have previously reported that during mouse tooth development, acetylcholinesterase (AChE) activity is dynamically localized in the dental epithelium and its derivatives whereas butyrylcholinesterase (BuChE) activity is localized in the dental follicles. To test the functional conservation of ChE in tooth morphogenesis among different species, we performed cholinesterase histochemistry following the use of specific inhibitors of developing molar and incisors in the hamster from embryonic day 11 (E11) to postnatal day 1 (P1). In the developing molar in hamster, the localization of ChE activity was found to be very similar to that of the mouse. At the bud stage, no ChE activity was found in the tooth buds, but was first detectable in the dental epithelium and dental follicles at the cap and bell stages. AChE activity was found to be principally localized in the dental epithelium whereas BuChE activity was observed in the dental follicle. In contrast to the ChE activity in the molars, BuChE activity was specifically observed in the secretory ameloblasts of the incisors, whilst no AChE activity was found in the dental epithelium of incisors. The subtype and localization of ChE activity in the dental epithelium of the incisor thus differed from those of the molar in hamster. In addition, these patterns also differed from the ChE activity in the mouse incisor. These results strongly suggest that ChE may play roles in the differentiation of the dental epithelium and dental follicle in hamster, and that morphogenetic subtypes of ChE may be variable among species and tooth types.
Acetylcholinesterase ; Ameloblasts ; Animals ; Butyrylcholinesterase ; Cartilage ; Cholinesterases ; Cricetinae ; Dental Sac ; Epithelium ; Incisor ; Mice ; Molar ; Morphogenesis ; Neurons ; Tooth ; Tooth Germ

BACKGROUND: In korea the agricultural community widely uses organophosphorous, and organophosphorous poisonings are increasing every year. We compared change in activity of acetylcholinesterase and pseudocholinesterase by organophosphorous and by the interaction of ethanol and organophosphorous. We also compared the effect of reversible anticholinesterase drugs, physostigmine and neostigmine. The object of this study is to investigate the effects of several anticholinesterase drugs and on how ethanol influences the activity of cholinesterase. MATERIALS AND METHODS: Fifteen male university students were randomly selected, and blood samples were taken from the antecubital vein. The acetylcholinesterase in the RBC and the pseudocholinesterase in the serum were extracted and separated. The enzyme activity change was measured by the electrometric method. After adding acetylcholine, the pH change was measured with a pH meter. RESULTS AND CONCLUSION: Our results indicated that reversible anticholinesterase drugs decreased the cholinesterase activity more efficiently than organophosphorous. The acetyl cholinesterase and pseudocholinosterase activity were decreased by ethanol. When ethanol was added, oxime a cholinesterase activator, increased acetylcholinesterase activity but dose not increased pseudocholinesterase activity.
Acetylcholine ; Acetylcholinesterase ; Cholinesterase Inhibitors ; Cholinesterases* ; Ethanol* ; Humans ; Hydrogen-Ion Concentration ; Korea ; Male ; Neostigmine ; Physostigmine ; Poisoning ; Pseudocholinesterase ; Veins

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.
Acetylcholinesterase ; Agaricales* ; Asian Continental Ancestry Group ; Butylated Hydroxytoluene ; Butyrylcholinesterase ; Cholinesterases ; Chromatography, Liquid ; Edema ; Fruit ; Galantamine ; Glutamic Acid ; Humans ; Hydroxyl Radical ; Inflammation ; Macrophages ; Methanol ; Models, Animal ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phenol ; Pleurotus*

Plasma cholinesterase was assayed during the period immediately following IV bolus injection of succinylcholine 1mg/kg to test the effect of succinylcholine on pseudocholinesterase activity. Twenty healthy adult patients scheduled for elective surgery were studied. The resutls were as follows: The mean value of pre-injection pseudocholinesterase activity was 1124.15 IU/L, and the activity following succinylcholin injection was 1159.55IU/L during fasciculation, 982.70 at 1 min, 936.60 at 3 min, 891.25 at 5 min, 926.80 at 7 min, 1015.45 at 10 min, and 1007.70 at 15 min. It was concluded that the tendency to increase pseuducholinesterase activity during fasciculation seems to be due to choline, the metabolite of succinylcholine, however the cause of the significant decrease in pseudocholinesterase activity after fasciculation is uncertain. The only suggested mechanism is due to the inhibition of pseudocholinesterase by succinylcholine and its metabolites.
Adult ; Choline ; Cholinesterases ; Fasciculation ; Humans ; Plasma ; Pseudocholinesterase ; Succinylcholine*

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.
Alzheimer Disease ; Butyrylcholinesterase ; Cholinesterases ; Chromatography, High Pressure Liquid ; Glycosides ; Lamiaceae ; Memory ; Plants ; Stachys

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.
Butyrylcholinesterase ; Catalytic Domain ; Cholinesterase Inhibitors ; Cholinesterases ; Computer Simulation ; Drug Design ; Garcinia ; Hydrogen Bonding ; In Vitro Techniques ; Quercetin ; Xanthones

The purpose of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on the activity of cholinesterases in vitro, and to investigate the mechanism of CIG's treating Alzheimer's disease (AD). The sources of cholinesterases were prepared from human blood cells, rat brain homogenate and human blood plasma, respectively. The biochemical methods were used to detect the activity of acetylcholine esterase (AChE) and butyryl cholinesterase (BuChE) to investigate the influence of CIG on cholinesterases. The results showed that CIG inhibited the activity of AChE of human blood cells and rat brain homogenate, with the 50% inhibition rate (IC50) of 1.6 g . L-1 and 3.3 g . L-1, respectively; and the inhibition of AChE of CIG is reversible. CIG also inhibited the activity of BuChE of human blood plasma, with the IC50 of 2.9 g . L-1. In conclusion, CIG can inhibit the activity of AChE and BuChE in vitro, which may be one of the mechanisms of CIG to treat AD.
Acetylcholinesterase ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Cholinesterases ; metabolism ; Humans ; Iridoid Glycosides ; pharmacology ; Plasma ; enzymology ; Rats

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.
Acetylcholinesterase ; Butyrylcholinesterase ; Juniperus ; Magnetic Resonance Spectroscopy

Pseudocholinesterase is known to be involved in the metabolism of succinylcholine, mivacurium, procaine, chloroprocaine, tetracaine, cocaine, heroin, and other drugs, although the physiologic function has not been well established. Prolonged neuromuscular block following administration of succinylcholine correlates with very low or genetically variant cholinesterase activity. The determination of pseudocholinesterase activity is of importance to the anesthetist in order to predict the susceptibility of the patient to the muscle relaxant, succinylcholine. The purpose of this study was to investigate the change of pseudocholinesterase level during cardiopulmonary bypass(CPB) for open heart surgery with hemodilution and hypothermia. Seven venous blood samples before induction of anesthesia(control), during CPB, and until the fifth postoperative day in 12 patients who underwent open heart surgery were taken. The pseudocholinesterase level was measured by Wako kit and JASCO UVIDEC 77 clinical spectrophotometer. The results were as follows ; 1) The control hematocrit was 40.32+/-6.21% and decreased to 23.72+/-1.86% immediately after the start of CPB(p<0.01) and to 22.42+/-1.93 % 30 minutes after the start of CPB(p<0.01). 2) The control pseudocholinesterase value of 1296.67+/-251.03 IU/L decreased to 915.67+/-228.16 IU/L immediately after the start of CPB(p<0.01), and to 727.83+/-197.58 IU/L 30 minutes after the start of CPB(p<0.01). 3) The mean values of pseudocholinesterase level immediately posteratively, on the first postoperative, and the third postoperative days were 1488.50+/-333.52 IU/L, 1913. 17+614.50 IU/L and 1620.92+/-458.82 IU/L, respectively, and those were significantly increased from the control value(p<0.05, p<0.01, and p<0.01, respectively). 4) The mean value of pseudocholinesterase level on the fifth postoperative day was 1392.25+/-271.69 IU/L, which was not significantly different from the control valule. 5) Transfused units of whole blood, packed red cells, and fresh frozen plasma were 2.8+/-1.4, 3.2 +/-1.0, 3.4+/-0.9, respectively.
Cardiopulmonary Bypass* ; Cholinesterases ; Cocaine ; Hematocrit ; Hemodilution ; Heroin ; Humans ; Hypothermia ; Metabolism ; Neuromuscular Blockade ; Plasma ; Procaine ; Pseudocholinesterase* ; Succinylcholine ; Tetracaine ; Thoracic Surgery