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Screening and identification of neuroprotective compounds relevant to Alzheimer׳s disease from medicinal plants of S. Tomé e Príncipe.
- Source :
-
Journal of ethnopharmacology [J Ethnopharmacol] 2014 Aug 08; Vol. 155 (1), pp. 830-40. Date of Electronic Publication: 2014 Jun 24. - Publication Year :
- 2014
-
Abstract
- Ethnopharmacological Relevance: Alzheimer׳s disease (AD) neuropathology is strongly associated with the activation of inflammatory pathways, and long-term use of anti-inflammatory drugs reduces the risk of developing the disease. In S. Tomé e Príncipe (STP), several medicinal plants are used both for their positive effects in the nervous system (treatment of mental disorders, analgesics) and their anti-inflammatory properties. The goal of this study was to determine whether a phenotypic, cell-based screening approach can be applied to selected plants from STP (Voacanga africana, Tarenna nitiduloides, Sacosperma paniculatum, Psychotria principensis, Psychotria subobliqua) in order to identify natural compounds with multiple biological activities of interest for AD therapeutics.<br />Materials and Methods: Plant hydroethanolic extracts were prepared and tested in a panel of phenotypic screening assays that reflect multiple neurotoxicity pathways relevant to AD-oxytosis in hippocampal nerve cells, in vitro ischemia, intracellular amyloid toxicity, inhibition of microglial inflammation and nerve cell differentiation. HPLC fractions from the extract that performed the best in all of the assays were tested in the oxytosis assay, our primary screen, and the most protective fraction was analyzed by mass spectrometry. The predominant compound was purified, its identity confirmed by ESI mass spectrometry and NMR, and then tested in all of the screening assays to determine its efficacy.<br />Results: An extract from the bark of Voacanga africana was more protective than any other plant extract in all of the assays (EC50s≤2.4 µg/mL). The HPLC fraction from the extract that was most protective against oxytosis contained the alkaloid voacamine (MW=704.90) as the predominant compound. Purified voacamine was very protective at low doses in all of the assays (EC50s≤3.4 µM).<br />Conclusion: These findings validate the use of our phenotypic screening, cell-based assays to identify potential compounds to treat AD from plant extracts with ethnopharmacological relevance. Our study identifies the alkaloid voacamine as a major compound in Voacanga africana with potent neuroprotective activities in these assays.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Alzheimer Disease drug therapy
Alzheimer Disease physiopathology
Animals
Atlantic Islands
Chromatography, High Pressure Liquid methods
Dose-Response Relationship, Drug
Ethnopharmacology
Humans
Ibogaine administration & dosage
Ibogaine isolation & purification
Ibogaine pharmacology
Magnetic Resonance Spectroscopy
Medicine, African Traditional methods
Mice
Neuroprotective Agents administration & dosage
Neuroprotective Agents isolation & purification
Plant Extracts administration & dosage
Rats
Spectrometry, Mass, Electrospray Ionization
Ibogaine analogs & derivatives
Neuroprotective Agents pharmacology
Plant Extracts pharmacology
Plants, Medicinal chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7573
- Volume :
- 155
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24971794
- Full Text :
- https://doi.org/10.1016/j.jep.2014.06.046