title: Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.
abstract: BACKGROUND
  Olax mannii Oliv. (Olacaceae) is among the many medicinal plants used in Nigeria for the ethnomedicinal management of both cancer and inflammation. Such plants represent potential sources of innovative therapeutic agents for the treatment of cancer and other malignant disorders. While the majority of medicinal plants exert their anticancer effects by direct cytotoxicity on tumor cells, it is important that other mechanisms through which these plants can exhibit anticancer effects are investigated. Preliminary studies indicated that Olax mannii leaves are rich sources of novel flavonoid glycosides. The detailed chemistry as well the mechanisms through which these flavonoid constituents may exert their cancer chemo-preventive and therapeutic effects are, however, not yet investigated.
  
  
  OBJECTIVE
  The aim of this study is to carry out a detailed chemical investigation of Olax mannii leaves and the effects of the isolated constituents on the nuclear factor kappa B (NF-κB) pathway.
  
  
  METHODS
  A methanol leaf extract was subjected to various chromatographic separations to achieve isolation of flavonoid glycosides and the structures of the isolated compounds were elucidated by a combination of 1D and 2D NMR and high resolution mass spectrometry. Biological activities were assessed by measurement of cellular viability and proliferation using quantitative IncuCyte videomicroscopy, trypan blue staining and by quantification of the number of metabolically active K562 cells based on quantitation of ATP. The effect of the compounds on the inhibition of the NF-κB pathway as well as toxicity towards peripheral blood mononuclear cells to evaluate differential toxicity was also assayed.
  
  
  RESULTS
  Chemical investigation of the methanol leaf extract of the plant material led to the isolation of three new flavonoid triglycosides, kaempferol 3-O-[α-D-apiofuranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (1), kaempferol 3-O-[β-D-glucopyranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (2), kaempferol 3-O-[β-D-arabinopyranosyl-(1→4)-α-L-rhamnopyranoside]-7-O-α-L-rhamnopyranoside (3), in addition to fourteen known flavonoid glycosides (4-17). Of all the tested compounds, only compound 9 (kaempferol 3-O-α-L-rhamnopyranoside) exhibited promising and specific antiproliferative activity on human K562 chronic myelogenous leukemia cells and dose-dependently inhibited NF-κB transactivation.
  
  
  CONCLUSIONS
  The presence of this flavonoid glycoside and derivatives may account for the reported efficacy of Olax mannii leaf extract in the ethnomedicinal management of cancer and inflammation.
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, HHU-Universität, Düsseldorf, Germany; Department of Pharmaceutical and Medicinal Chemistry, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria. Electronic address: fb.okoye@unizik.edu.ng.
authors.forename: Festus B C
authors.initials: FB
authors.lastname: Okoye
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, Luxembourg.
authors.forename: Wamtinga Richard
authors.initials: WR
authors.lastname: Sawadogo
authors.affiliation: University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany.
authors.forename: Jandirk
authors.initials: J
authors.lastname: Sendker
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, HHU-Universität, Düsseldorf, Germany.
authors.forename: Amal H
authors.initials: AH
authors.lastname: Aly
authors.affiliation: University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Quandt
authors.affiliation: Helmholtz Centre for Infection Research, Inhoffenstrasse 7, d-38124 Braunschweig, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Wray
authors.affiliation: University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hensel
authors.affiliation: Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
authors.forename: Charles O
authors.initials: CO
authors.lastname: Esimone
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, HHU-Universität, Düsseldorf, Germany.
authors.forename: Abdessamad
authors.initials: A
authors.lastname: Debbab
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
authors.affiliation: Institut für Pharmazeutische Biologie und Biotechnologie, HHU-Universität, Düsseldorf, Germany. Electronic address: proksch@uni-duesseldorf.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D031656:Olacaceae; D018515:Plant Leaves / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; D006027:Glycosides; D016328:NF-kappa B
keywords: Cytotoxicity; Kaempferol glycosides; NF-κb; Olacaceae; Olax mannii; Proliferation