[en] OBJECTIVES: 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. KEY FINDINGS: 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Murebwayire, Sengabo
Ingkaninan, Kornkanok
Changwijit, Kanokwan
Frederich, Michel ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Duez, Pierre
Language :
English
Title :
Triclisia sacleuxii (Pierre) Diels (Menispermaceae), a potential source of acetylcholinesterase inhibitors.
Zurad EG. New treatments for Alzheimer's disease: a review. Drug Benefit Trends 2001: 13: 27-40.
US National Institute on Aging (2005). Progress report on Alzheimer's disease 2004-2005. Part 3: Alzheimer's Disease Research Advances. US National Institutes of Health. http://www.nia.nih.gov//Alzheimers (accessed 22 September 2007).
Katzman R. Alzheimer's disease. N Engl J Med 1986: 314: 964-973.
Geula C. Mesulam MM. Cholinergic systems and related neuropathological predilection patterns in Alzheimer disease. In: Terry RD et al. eds. Alzheimer's Disease. New York: Raven Press, 1994: 263-291.
Schorderet M. Alzheimer's disease: Fundamental and therapeutic aspects. Experientia 1995: 51: 99-105.
Rhizzi A et al. Enantiomeric resolution of galanthamine and related drugs used in anti-Alzheimer therapy by means of capillary zone electrophoresis employing derivatized cyclodextrin selectors. J Chromatogr B 1999: 730: 167-175.
Rhee IK et al. Screening for acetylcholinesterase inhibitors from Amaryllidaceae using silica gel thin-layer chromatography in combination with bioactivity staining. J Chromatogr A 2001; 915: 217-223.
Lopez S et al. Acetylcholinesterase inhibitory activity of some Amaryllidaceae alkaloids and Narcissus extracts. Life Sci 2002; 71: 2521-2529.
Ingkaninan K et al. Screening for acetylcholinesterase inhibitory activity in plants used in Thai traditional rejuvenating and neurotonic remedies. J Ethnopharmacol 2003; 89: 261-264.
Ashani Y et al. Role of tyrosine 337 in the binding of huperzine A to the active site of human acetylcholinesterase. Mol Pharmacol 1994; 45: 555-560.
Tang XC et al. Comparison of the effects of natural and synthetic huperzine-A on rat brain cholinergic function in vitro and in vivo. J Ethnopharmacol 1994; 44: 147-155.
Orhan I et al. Acetylcholinesterase and butyrcholinesterase inhibitory activity of some Turkish medicinal plants. J Ethnopharmacol 2004; 91: 57-60.
Ogino T et al. Studies on inhibitory activity against acetylcholinesterase of new bisbenzylisoquinoline alkaloid and its related compounds. Heterocycles 1997; 45: 2253-2260.
Markmee S et al. Isoquinoline derivatives as potential acetylcholinesterase inhibitors. Bioorg Med Chem Lett 2006; 16: 2170-2172.
Ingkaninan K et al. Vobasinyl-iboga bisindol alkaloids, potent acetylcholinesterase inhibitors from Tabernaemontana divaricata root. J Pharm Pharmacol 2006; 58: 847-852.
Murebwayire S et al. Alkaloids and amides from T sacleuxii (Pierre) Diels. Fitoterapia 2006; 77: 615-617.
Kanyinda B et al. Bisbenzylisoquinoline alkaloids from Anisocycla cymosa roots. J Nat Prod 1992; 55: 607-612.
Ellman GL et al. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7:88-95.
Duté P et al. Bis-Benzylisoquinoline alkaloids from Abuta pahni. Phytochem 1987; 26: 2136-2137.
Murebwayire S et al. Antiplasmodial and antitrypanosomal activity of Triclisia sacleuxii (Pierre) Diels. Phytomedicine 2008; (in press).
Rhee IK et al. Qualitative determination of false-positive effects in the acetylcholinesterase assay using thin-layer chromatography, Phytochem Anal 2003; 14: 127-131.