Novel polyacetylene derivatives and their inhibitory activities on acetylcholinesterase obtained from Panax ginseng roots.

In our research program to identify cholinesterase and ß-secretase inhibitors, we investigated Ginseng (root of Panax ginseng), a crude drug described as a multifunctional drug in the ancient Chinese herbal book Shennong Ben Cao Jing. Results from hexane and methanol extracts showed moderate inhibitory activities. This suggests that ginseng roots may be effective for the prevention of and therapy for dementia. We then focused on hexane extracts of raw ginseng root and dried ginseng root since the determination of hexane extract constituents has not been studied extensively. Activity-guided fractionation and purification led to the isolation of 4 polyacetylene compounds; homopanaxynol, homopanaxydol, (9Z)-heptadeca-1, 9-diene-4,6-diyn-3-one, and (8E)-octadeca-1,8-diene-4,6-diyn-3,10-diol. The chemical structures of these compounds, including stereochemistry, were determined. This is the first study to identify the structure of homopanaxynol and homopanaxydol. Moreover, the modes of action of some compounds were characterized as competitive inhibitors. This study showed, for the first time, that polyacetylene compounds possess acetylcholinesterase inhibitory activities.

Screening of ß-secretase and acetylcholinesterase inhibitors from plant resources.

The therapeutic agents for dementia are limited due to the complex system underlying the mechanisms. Taking a preventive point of view, we focused on the inhibition of ß-secretase and acetylcholinesterase (AChE). In addition, plant resources including herbs and spices have been widely consumed, and further, may be consumed for a long period over a lifetime. Considering this background, we screened ß-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit ß-secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of ß-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, α- and ß-caryophyllene, ß-caryophyllene oxide (from curry leaf), piperine (from black pepper), curcumin, demethoxycurcumin, and bisdemethoxycurcumin (from turmeric) were successfully identified as low molecular inhibitors. This is the first report to determine α- and ß-caryophyllene, ß-caryophyllene oxide, and piperine as ß-secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low.

Design of a new multi-turn ion optical system 'IRIS' for a time-of-flight mass spectrometer.

A new multi-turn ion optical system 'IRIS' has been designed for use with a high-performance time-of-flight (TOF) mass spectrometer, which satisfies the new design concepts of time focusing and phase space stability. It has an elliptical flight path composed of four toroidal electric sectors, with a flight path length for one lap of 0.974 m. Dimensions and voltages of sector electrodes have been optimized to satisfy theoretical requirements by simulations using surface charge method. Generally, multi-turn instruments require an injection and ejection system to inject and eject ions. On the basis of this ion optical study, we have designed an injection and ejection ion optical system, which achieves time focusing for the total system. Furthermore, we have designed novel field-adjusting electrodes (FAEs) for the perforated sectors in the injection and ejection systems, which accurately correct the electric potential around the perforated sector's hole. We have also used simulations to evaluate mass resolving power and ion transmissions for various lap numbers or flight path lengths. Through these we have confirmed that mass resolving powers of over 100,000 can be achieved with reasonable ion transmissions for a given set of initial conditions. Usually a multi-turn TOF mass spectrometer with a closed optic axis has mass range limitations from overtaking ions. To solve this problem, a TOF segmentation method is proposed that identifies all peaks in a TOF spectrum, including those from overtaking ions.