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United States Department of Agriculture

Agricultural Research Service

Research Project: CONSERVATION, CHARACTERIZATION, AND GENETIC IMPROVEMENT OF SUBTROPICAL AND TROPICAL ORNAMENTAL GERMPLASM Title: Phylogenetic selection of target species in Amaryllidaceae tribe Haemantheae for acetylcholinesterase inhibition and affinity to the serotonin reuptake transport protein

Authors
item Bay-Smidt, Mette -
item Jager, A -
item Krydsfeldt, K -
item Meerow, Alan
item Stafford, G -
item Van Staden, -
item Ronsted, Nina -

Submitted to: South African Journal of Botany
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 28, 2010
Publication Date: August 30, 2010
Citation: Bay-Smidt, M.B., Jager, A.K., Krydsfeldt, K., Meerow, A.W., Stafford, G.I., Van Staden, Ronsted, N. 2010. Phylogenetic selection of target species in Amaryllidaceae tribe Haemantheae for acetylcholinesterase inhibition and affinity to the serotonin reuptake transport protein. South African Journal of Botany. DOI: 10.1016/j.sajb.2010.07.016.

Interpretive Summary: We present evolutionary trees based on nuclear and chloroplast DNA sequences across 37 taxa of the African berry-fruited Amaryllidaceae (tribe Haemantheae) in order to identify candidate species with potential bioactivity in relation to Alzheimer´s disease and depression. Within the genus Haemanthus, a well supported group corresponds to a summer rainfall group (mainly Eastern Cape) with white-pale pink flowers; a second strongly supported group corresponds to a winter rainfall group (mainly Western Cape) with red to pale pink flowers. Haemanthus montanus, which is from the summer rainfall region, is sister to the winter rainfall group. Alkaloid profiles and bioactivity profiles were investigated for 16 taxa. No alkaloids were detected in extracts of the two species of Gethyllis included in the present study suggesting that Gethyllis (and possibly Apodolirion) species may not produce the alkaloids characteristic for the family. AChE inhibitory activity was found in all investigated evolutionary groups except the Apodolirion-Gethyllis lineage, which can be explained by the apparent lack of alkaloids in this clade. Within tribe Haemantheae, dose-dependent SERT activity appears to be pronounced and restricted to the genus Haemanthus. Two of the most active extracts in the present study contained primarily pancracine type alkaloids which have not been tested for SERT affinity previously.

Technical Abstract: We present phylogenetic analyses of 37 taxa of Amaryllidaceae, tribe Haemantheae and Amaryllis belladonna L. as an outgroup, in order to provide a phylogenetic framework for the selection of candidate plants for lead discoveries in relation to Alzheimer´s disease and depression. DNA sequences from the nuclear ribosomal internal transcribed spacer (ITS) and the plastid trnL-F regions were used. Maximum parsimony analyses provide increased support for the sister relationship of Haemanthus and Scadoxus. Within Haemanthus, a well supported clade (89 % BS) corresponds to a summer rainfall group (mainly Eastern Cape) with white-pale pink flowers. A second strongly supported clade (100 % BS) corresponds to a winter rainfall group (mainly Western Cape) with red to pale pink flowers. Haemanthus montanus, which is from the summer rainfall region, is sister to the winter rainfall group. Alkaloid profiles and bioactivity profiles were investigated for 16 taxa using gas chromatography-mass spectrometry (GC-MS) and assays measuring acetylcholinesterase (AChE) inhibition and affinity to the serotonin reuptake transport protein (SERT). No alkaloids were detected by GC-MS in extracts of the two species of Gethyllis included in the present study suggesting that Gethyllis (and possibly Apodolirion) species may not produce the alkaloids characteristic for the family. AChE inhibitory activity was found in all investigated clades except the Apodolirion-Gethyllis clade, which can be explained by the apparent lack of alkaloids in this clade. Within tribe Haemantheae, dose-dependent SERT activity appears to be pronounced and restricted to the genus Haemanthus. Three of eight Haemanthus species tested had IC50 < 10 µg/ml. Two of the most active extracts in the present study contained primarily pancracine type alkaloids which have not been tested for SERT affinity previously. Simultaneous evaluation of bioactivity and alkaloid profiles in a phylogenetic framework can potentially be used to select candidate species for phytotherapy and drug discovery.

Last Modified: 10/20/2014
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