PUBLICATION

Using Ultra-Performance Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry-Based Chemometrics for the Identification of Anti-angiogenic Biflavonoids from Edible Garcinia Species

Authors
Li, P., Yue, G.G., Kwok, H.F., Long, C.L., Lau, C.B., Kennelly, E.J.
ID
ZDB-PUB-170920-4
Date
2017
Source
Journal of Agricultural and Food Chemistry   65(38): 8348-8355 (Journal)
Registered Authors
Keywords
Garcinia xanthochymus, PCA, UPLC−QTOF−MS, anti-angiogenesis, biflavonoids
MeSH Terms
  • Angiogenesis Inhibitors/chemistry*
  • Angiogenesis Inhibitors/pharmacology
  • Animals
  • Chromatography, High Pressure Liquid
  • Fruit/chemistry
  • Garcinia/chemistry*
  • Humans
  • Mass Spectrometry
  • Neovascularization, Pathologic/drug therapy
  • Neovascularization, Pathologic/genetics
  • Neovascularization, Pathologic/metabolism
  • Plant Extracts/chemistry*
  • Plant Extracts/pharmacology
  • Structure-Activity Relationship
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/metabolism
PubMed
28926234 Full text @ J. Agric. Food Chem.
Abstract
Garcinia xanthochymus fruits are edible and also used in traditional medicine. Our previous work showed that the isolated natural products from G. xanthochymus fruits have displayed antioxidant activity and cytotoxicity in the colon cancer cells. In this study, we developed a strategy to correlate a zebrafish angiogenesis assay with ultra-performance liquid chromatography quadrupole time of flight mass spectrometry-based chemometric analysis to identify potential anti-angiogenic activity compounds from G. xanthochymus fruits. Primary bioactivity results showed that the methanolic extracts from aril and pericarp but not from seed have significant inhibitory effects on the growth of subintestinal vessels (SIVs) in zebrafish embryos. A total of 13 markers, including benzophenones and biflavonoids, were predicted by untargeted principal component analysis and orthogonal partial least squares discriminate analysis, which were tentatively identified as priority markers for the bioactivity related in aril and pericarp. Amentoflavone, a biflavonoid, has been found to significantly inhibit the growth of SIVs at 10 and 20 μM and downregulate the expressions of Angpt2 and Tie2 genes of zebrafish embryos. Furthermore, seven biflavonoids, volkensiflavone, fukugetin, fukugeside, GB 1a, GB 1a glucoside, GB 2a, and GB 2a glucoside, isolated from Garcinia species were evaluated for their structure-activity relationship using the zebrafish model. Only fukugetin, which was previously shown to be anticancer, was active in inhibiting the SIV growth. In this report, both amentoflavone and fukugetin, for the first time, displayed anti-angiogenic effects on zebrafish, thus demonstrating an effective and rapid strategy to identify natural products for anti-angiogenesis activity.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping