Murata_2015_J.Nat.Med_69_123

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 beta-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 beta-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit beta-secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of beta-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, alpha- and beta-caryophyllene, beta-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 alpha- and beta-caryophyllene, beta-caryophyllene oxide, and piperine as beta-secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low.