Inhibition Of Rat Brain Acetylcholinesterase Research Articles

In vitro antioxidant and cholinesterase inhibitory activities of methanolic fruit extract of Phyllanthus acidus.

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder clinically characterized by loss of memory and cognition. Cholinergic deficit and oxidative stress have been implicated in the pathogenesis of AD. Therefore, inhibition of acetylcholinesterase and oxidation are the two promising strategies in the development of drug for AD. Phyllanthus acidus, belonging to the family Euphorbiaceae, is a tree and has been used in traditional medicine to treat several pain, inflammatory and oxidative stress related disorders such as rheumatism, bronchitis, asthma, respiratory disorder, also important to promote intellect and enhance memory, thus supporting its possible anti-Alzheimer’s properties. In this study, P. acidus was evaluated for its cholinesterase inhibitory and antioxidant activities.MethodsIn this study, we evaluated the antioxidant potential and neuroprotective activity of P. acidus by assessing total phenol content (FCR assay), total flavonoid content, total antioxidant capacity, Fe3+ reducing power capacity, DPPH (2, 2-diphenyl-1-picrylhydrazyl) and hydroxyl radical scavenging capacity, lipid peroxidation inhibition activity & metal chelating activity. In addition acetylcholinestrase (AChE) and butyrylcholinestrase (BChE) inhibitory activities were performed using Ellman’s method.ResultsTotal phenolic content and total flavonoid content of the extract were 116.98 mg of gallic acid equivalent and 168.24 mg of quercetin equivalent per gm of dried extract. The methanolic extract of P. acidus (MEPA) showed considerable total antioxidant activity and reducing capacity. In DPPH scavenging assay and hydroxyl radical scavenging assay, the MEPA showed 84.33 % and 77.21 % scavenging having IC50 of 15.62 and 59.74 μg/ml respectively. In lipid peroxidation inhibition activity MEPA showed moderate inhibition of peroxidation at all concentrations with IC50 value of 471.63 μg/ml and exhibited metal chelating activity with IC50 value 308.67 μg/ml. The MEPA exhibited inhibition of rat brain acetylcholinesterase and human blood butyrylcholinesterase in a dose dependent manner and the IC50 value was found to be 1009.87 μg/ml and 449.51 μg/ml respectively.ConclusionThese results of the present study reveal that MEPA has considerable amount of antioxidant activity as well as anti-acetylcholinesterase and anti-butyrylcholinesterase activity which suggest its effectiveness against Alzheimer's disease and other neurodegenerative disorders.

STRUCTURAL CONSIDERATION IN THE INHIBITION OF RAT BRAIN ACETYLCHOLINESTERASE.

STRUCTURAL CONSIDERATION IN THE INHIBITION OF RAT BRAIN ACETYLCHOLINESTERASE.

Anticholinesterase activities of cold and hot aqueous extracts ofF. racemosastem bark

The present study evaluated the anticholinesterase activity of cold and hot aqueous extracts of Ficus racemosa stem bark against rat brain acetylcholinesterase in vitro. Both the cold aqueous extract (FRC) and the hot aqueous extract (FRH) exhibited a dose dependent inhibition of rat brain acetylcholinesterase. FRH showed significantly higher (P ≤ 0.001) cholinesterase inhibitory activity compared to FRC; however, both the extracts did not show 50% inhibition of AChE at the doses tested (200-1000 μg ml−1). The IC50 values of 1813 and 1331 μg ml−1 were deduced for FRC and FRH, respectively (calculated by extrapolation using Boltzmann's dose response analysis).

Kinetics of the postinhibitory reactions of acetylcholinesterase poisoned by chiral isomalathion: a surprising nonreactivation induced by the RP stereoisomers.

Inhibitory (ki), spontaneous (k0), and oxime-mediated reactivation (k(oxime)) reaction kinetics for the four stereoisomers of isomalathion (SPRC,SPSC,RPRC, and RPSC) were determined against rat brain acetylcholinesterase (AChE). (SPRC)-Isomalathion was the most potent anticholinesterase agent and RPSC-isomalathion the least potent with racemic material approximately midway in activity. Following inhibition of rat brain AChE by (SPRC)- or (SPSC)-isomalathion, k0 and k(oxime) values were obtained that were comparable to (SP)-isoparathion methyl, indicating that the same mechanism of inhibition was shared, namely, formation of an O,S-dimethyl phosphorothiolated enzyme. Conversely, no appreciable reactivation occurred with or without oxime following inhibition of rat brain AChE by (RPSC)- or (RPRC)-isomalathion. This observation was not consistent with (RP)-isoparathion methyl, and a switch in inhibition mechanism to the loss of the thiomethyl moiety is suggested. The nonreactivation of rat brain AChE following inhibition by the (RP)-isomalathion stereoisomers is postulated to result from a mechanism involving either a beta-elimination of diethyl fumarate or displacement of the thiosuccinate moiety from the phosphate moiety.

Anisomycin, acetoxycycloheximide, cycloheximide, and puromycin as inhibitors of rat brain acetylcholinesterase in vitro.

AbstractA kinetic analysis of the interaction of anisomycin, acetoxycycloheximide, cycloheximide, and puromycin with acetylcholinesterase (acetylcholine acetyl‐hydrolase, EC 3.1.1.7) in rat brain homogenate shows that all of these protein synthesis inhibitors are also inhibitors or this enzyme. Puromycitl aminonucleoside, a puromycin analog without antibiotic activity, was also found to be an inhibitor of acetylcholinesterase activity much like puromycin. Anisomycin appeared to be a competitive inhibitor whereas all of the other compounds showed mixed inhibition. The apparent 10.5 values for inhibition of rat brain acetylcholinesterase at 50 μM substrate were: anisomycin, 3 mM; acetoxycycloheximide, 1 mM; cycloheximide, 2.2 mM; puromycin, 0.5 mM and puromycin aminonucleoside, 0.6 mM.

Kinetics of inhibition of rat brain acetylcholinesterase by 3-diethylaminophenyl-N-methyl- and -N-phenylcarbamate methoiodide in vitro

Kinetics of inhibition of rat brain acetylcholinesterase by 3-diethylaminophenyl-N-methyl- and -N-phenylcarbamate methoiodide in vitro

Puromycin as an inhibitor of rat brain acetylcholinesterase

Puromycin is an effective mixed inhibitor of rat brain acetylcholinesterase at concentrations below those used in memory studies. This kinetic analysis indicates that the concentration of puromycin which gives 50% inhibition of rat brain acetylcholinesterase at 50 μM substrate is approximately 0.5 mM. The results suggest that puromycin binds at two classes of sites on the enzyme, one of which appears to be an allosteric site. Since the allosteric site of acetylcholinesterase has properties similar to the acetylcholine receptor and appears to bind most ligands that bind to the acetylcholine receptor, this evidence supports the idea that puromycin may also block the effect of acetylcholine at the synaptic membrane. Puromycin may interfere with the recall of memory by causing direct interference with cholinergic mechanisms.

On the kinetics of inhibition of rat-brain acetylcholine esterase by Sevin.

The inhibition of rat-brain acetylcholinesterase with Sevin was shown to be partly reversible. The rate of progression of the irreversible inhibition is extremely slow and follows the kinetics of a unimolecular reaction, with Κ=3.65 · 10-3 min-1 and t 0.5 190 minutes. The reversible inhibition of the enzyme was found to be of competitive nature. The dissociation constant of E — I (Ki) was determined —by two different methods —to be 5.7 and 7.6 · 10-6 Μ. The presence of acetylcholine protects the enzyme against the irreversible attack of Sevin. It is believed that acetylcholine esterase does not participate in the biological degradation of Sevin in the nervous tissue.