Triclisia sacleuxii (Pierre) Diels (Menispermaceae), a potential source of acetylcholinesterase inhibitors.
OBJECTIVE
To search for compounds possibly useful for the treatment of Alzheimer's disease.


METHODS
Alkaloid fractions from the roots, stems and leaves of Triclisia sacleuxii (Menispermaceae) and pure bisbenzylisoquinoline alkaloids isolated from the roots (phaeanthine, N-methylapateline, 1,2-dehydroapateline and gasabiimine) were assessed for acetylcholinesterase inhibitory activity.


RESULTS
All extracts and compounds tested inhibited acetylcholinesterase to varying degrees; the leaf tertiary alkaloid fractions and the root quaternary alkaloid fractions exhibited the strongest inhibitory potential (90% at 0.1 mg/ml). The leaf tertiary alkaloid fraction was selected for further analysis (the quaternary alkaloids, which are too polar for absorption and brain distribution, were presumed to be clinically uninteresting). TLC bioautography using Ellman's reagent allowed the detection of acetylcholinesterase inhibitors and the isolation of the major active constituent, which was identified as lindoldhamine, a one-bridged bisbenzylisoquinoline alkaloid. Lindoldhamine displayed high acetylcholinesterase inhibitory activity with a 50% inhibition concentration in the micromolar range.


CONCLUSIONS
All T. sacleuxii alkaloid fractions tested exhibited anti-acetylcholinesterase activity; isolated bisbenzylisoquinoline alkaloids showed weak-to-high inhibition depending on their structural features. Structure modification could provide interesting derivatives with enhanced anti-acetylcholinesterase activity.
Murebwayire
Sengabo
S
Laboratory of Pharmacognosy, Bromatology and Human Nutrition, Institute of Pharmacy, Free University of Brussels (ULB), Brussels, Belgium.
Ingkaninan
Kornkanok
K
Changwijit
Kanokwan
K
Frédérich
Michel
M
Duez
Pierre
P
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D044182:Benzylisoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005591:Chemical Fractionation / Q000379:methods; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D029583:Menispermaceae / Q000737:chemistry*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry
D000470:Alkaloids; D044182:Benzylisoquinolines; D002800:Cholinesterase Inhibitors; D010936:Plant Extracts; C038606:phaeanthrine