Acetylcholinesterase inhibitory activities of 48 traditional Chinese medicinal herbs

Inhibition of acetylcholinesterase （ACHE） is one of the approaches for the treatment of Alzheimer＇s disease （AD）. In this paper the AChE inhibitory activities of ethanolic and aqueous extracts of 48 traditional Chinese medicinal herbs were evaluated. These traditional Chinese medicines have intelligence-promoting, anti-insomnia, sedative, neurotonic or tonic effects. Microplate assay indicated that ethanolic extracts of 28 traditional Chinese medicinal herbs and water extracts of 11 herbs showed AChE inhibitory activities. Among them, ethanolic extracts of Herba Moslae, Fructus Alpiniae Oxyphyllae, Radix Rehmanniae and Folium Nelumbinis showed most potent AChE inhibitory activities at the concentration of 0.1 mg/mL, with （68.63±1.12）%, （44.49±3.66）%, （43.78±4.76）%, and （42.63±8.31）% inhibition, respectively. The AChE inhibitory activities were also confirmed by TLC bioautographic assay. These results partially validate the traditional uses of some medicinal herbs for cognitive improvement.

Ameliorating effects of constituents from Cortex Acanthopanacis Radicis on memory impairment in mice induced by scopolamine

OBJECTIVE:To investigate the effects of active constituents extracted from Cortex Acanthopanacis Radicison improving the impaired memory in mice models.METHODS:The mice models of memory impairment were established using scopolamine.Ameliorating effects of the fractions and constituents on scopolamine-induced memory impairment in vivo were investigated using passive avoidance and Morris water-maze task tests,and their anti-acetylcholinesterase(AChE)and antioxidant activities in vitro examined.The isolation of constituents was performed by chromatographic methods and their structures were identified on the basis of instrumental analysis.RESULTS:Among the fractions tested,ethylacetate fraction exhibited the anti-AChE activity(25.83%±0.23%)properly and excellent 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical and superoxide anion scavenging capacity(87.50%±0.83%and 60.22%±0.43%,respectively).However,the methylene chloride fraction was much more active than the ethylacetate fraction in the passive avoidance task test(167.5%increase of step-through latency time)and Morris water-maze task test(33.3%decrease of es-cape latency time).Four constituents,β-sitosterol,stigmasterol,sesamin,and hyperin were isolated from the methylene chloride fraction,among them,hyperin showed anti-acetylcholinesterase and anti-oxidant activities remarkably.Moreover,hyperin exerted a potent effect(146±38)s on memory improvement in terms of passive avoidance task test compared with the reference compound tacrine(162±43)s at a dose of 2.5 mg/kg.CONCLUSION:Hyperin,a flavonoid glucoside isolated from Cortex Acanthopanacis Radicis,inhibited AChE activity and potently ameliorated scopolamine-induced memory impairment,and its action may be partially mediated by the acetylcholine-enhancing cholinergic nervous system.

Design, synthesis and biological evaluation of novel quinoline [4,3-b] chromene derivatives as AChE inhibitors through an efficient one-pot, four-component microwave-mediated reaction

An efficient synthesis of chromeno[4,3-b]quinoline derivatives via one-pot,four-component reaction of 4-hydroxycoumarin, formaldehyde,cyclohexanedione,ammonium ceric nitrate under microwave irradiation was accomplished.The structures of these compounds were unambiguously confirmed by single crystal X-ray diffraction.Furthermore,the anti-AChE activities of these compounds in vitro were investigated at concentrations of 20μM and 50μM by using a standard Ellman's method.The relationship of inhibitory activities and structures of these chromeno [4,3-b]quinolines was also systematically studied.Of all the compounds investigated,4ag emerged as the most potent AChE inhibitor with IC50 values of 5.63μM,and it might be used as potent lead for the development anti-AChE agents.Moreover,molecular modelling was conducted to understand the optimal interaction of AChE with these types of compounds.