Anticholinesterase activity of 7-methoxyflavones isolated from Kaempferia parviflora.
The rhizome of Kaempferia parviflora or kra-chai-dum (in Thai) is used traditionally as a folk medicine. The preliminary cholinesterase inhibitory screening of this plant extract exhibited significant acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Thirteen known methoxyflavones (1-13) were isolated and their structures were completely elucidated based on NMR analysis and compared with literature reports. Minor compounds 12-13 were reported for the first time from this species. The cholinesterase inhibitory test results showed that the highest potential inhibitors toward AChE and BChE were 5,7,4'-trimethoxyflavone (6) and 5,7-dimethoxyflavone (7), respectively, with the percentage inhibitory activity varying over 43-85%. The structure-activity relationship study led to the conclusion that compounds bearing 5,7-dimethoxy groups and a free substituent at C-3 had a significant inhibitory effect at a concentration of 0.1 mg/mL, but those bearing a 5-hydroxyl group reduced the inhibitory potency. On the other hand, flavones bearing a 3'- or 5'-methoxy group did not influence the inhibitory effect. Interestingly, 5,7-dimethoxyflavone (7) exhibited strong selectivity for BChE over AChE which may be of great interest to modify as a treatment agent for Alzheimer's disease.
Sawasdee
Pattara
P
Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. spattara@windowslive.com
Sabphon
Chalisa
C
Sitthiwongwanit
Duangporn
D
Kokpol
Udom
U
D000110:Acetylcholinesterase / Q000378:metabolism; D047310:Apigenin / Q000302:isolation & purification / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D008518:Medicine, East Asian Traditional; D015394:Molecular Structure; D010936:Plant Extracts / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry; D013329:Structure-Activity Relationship; D030521:Zingiberaceae / Q000737:chemistry*
D002800:Cholinesterase Inhibitors; D005419:Flavonoids; D010936:Plant Extracts; C060298:5,7-dimethoxyflavone; C103112:5,7,4'-trimethylapigenin; D047310:Apigenin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase