Searching for immunomodulatory compounds from Icelandic marine invertebrates

• Main Author: Di, Xiaxia
• Other Authors: Sesselja Sigurborg Ómarsdóttir; Jóna Freysdóttir og Ingibjörg Harðardóttir, Lyfjafræðideild (HÍ), Faculty of Pharmaceutical Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: University of Iceland, School of Health Sciences, Faculty of Pharmaceutical Sciences 2019
• Subjects: Marine natural products; Marine invertebrates; Immunomodulatory; Anti-inflammatory; Iceland; Alkaloids; Lipids; Sjávarnáttúruefni; Sjávardýr; Hryggleysingjar; Ónæmisfræði; Fituefni; Bólgueyðandi; Lyfjafræði; Doktorsritgerðir
• Online Access: https://hdl.handle.net/20.500.11815/966

A substantial diversity of secondary metabolites from marine invertebrates has been described; however, only a few studies have investigated secondary metabolites of marine invertebrates collected in Icelandic waters. The unique marine environment around Iceland, in terms of temperature and underwater geothermal activity, has forced the living marine organisms to survive in the surroundings by developing unique biomolecules. The marine invertebrates are therefore an excellent starting point for searching for new bioactive compounds. The aim of this thesis was to isolate and identify new compounds, and known, with immunomodulatory activity from marine invertebrates collected in Icelandic waters. Seven crude extracts from Icelandic marine sponges were screened for immunomodulatory activities using an in vitro dendritic cell (DC) model. The bioactive extracts were then fractionated by column chromatographic technique with the help of bioassay-guided isolation approach to isolate the active constituents. Five pure known polyunsaturated fatty acids (PUFAs) from unidentified marine sponges and several lipophilic fractions from Halichondria sitiens were obtained and they showed immunomodulatory activity, demonstrated by their ability to reduce DC secretion of the pro-inflammatory cytokine IL-12p40 and the anti-inflammatory cytokine IL-10. Maturing DCs in the presence of selected fractions before co-culturing them with allogeneic CD4+ T cells mainly led to a decrease in T cell secretion of IFN-y, indicating a reduction in Th1 immune response. In addition, one new glycerol ester featuring methyl branched fatty acid chain was obtained but it did not have immunomodulatory activity using the DC model. Crude extracts from the marine sponge Geodia barretti and the bryozoan Flustra foliacea were chemically profiled by UPLC-qTOF-MS. Both previously known and unknown compounds were characterized by comparing the obtained molecular (precursor) ions and fragmentation patterns from obtained MS/MS data with data from the literature ...