title: Screening and identification of neuroprotective compounds relevant to Alzheimer׳s disease from medicinal plants of S. Tomé e Príncipe.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: acurrais@salk.edu.
authors: Antonio
authors: A
authors: Currais
authors: The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Chandramouli
authors: C
authors: Chiruta
authors: The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Marie
authors: M
authors: Goujon-Svrzic
authors: Center for Pharmaceutical Studies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; Center for Neurosciences and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal.
authors: Gustavo
authors: G
authors: Costa
authors: Center for Pharmaceutical Studies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; Center for Neurosciences and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal.
authors: Tânia
authors: T
authors: Santos
authors: Center for Pharmaceutical Studies, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; Center for Neurosciences and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal.
authors: Maria Teresa
authors: MT
authors: Batista
authors: Centre for Functional Ecology, Department of Life Sciences, University of Coimbra, 3004-516 Coimbra, Portugal.
authors: Jorge
authors: J
authors: Paiva
authors: Centre for Functional Ecology, Department of Life Sciences, University of Coimbra, 3004-516 Coimbra, Portugal.
authors: Maria
authors: M
authors: do Céu Madureira
authors: The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Pamela
authors: P
authors: Maher
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D001266:Atlantic Islands; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D020834:Ethnopharmacology; D006801:Humans; D007050:Ibogaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D016488:Medicine, African Traditional / Q000379:methods; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D018696:Neuroprotective Agents; D010936:Plant Extracts; C005891:voacamine; D007050:Ibogaine
keywords: Aging; Alzheimer; Dementia; Inflammation; Neurodegenerative disorders; Traditional medicine Africa