title: Screening of β-secretase and acetylcholinesterase inhibitors from plant resources.
abstract: 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 β-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 β-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit β-secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of β-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, α- and β-caryophyllene, β-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 β-caryophyllene, β-caryophyllene oxide, and piperine as β-secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low.
authors.affiliation: Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Murata
authors.forename: Shinichi
authors.initials: S
authors.lastname: Matsumura
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ueno
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000110:Acetylcholinesterase; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D052117:Benzodioxoles / Q000737:chemistry / Q000302:isolation & purification; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification; D036381:Diarylheptanoids; D032101:Murraya / Q000737:chemistry; D029222:Piper nigrum / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D000081223:Polycyclic Sesquiterpenes; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000302:isolation & purification; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D002800:Cholinesterase Inhibitors; D036381:Diarylheptanoids; D010880:Piperidines; D010936:Plant Extracts; D000081223:Polycyclic Sesquiterpenes; D053284:Polyunsaturated Alkamides; D012717:Sesquiterpenes; C034786:bisdemethoxycurcumin; C012596:turmeric extract; C024714:caryophyllene; D000110:Acetylcholinesterase; D053829:Amyloid Precursor Protein Secretases; D003474:Curcumin; C515179:caryophyllene oxide; C008922:piperine; C050229:demethoxycurcumin