Open AccessDysivillosins A–D, Unusual Anti-allergic Meroterpenoids from the Marine Sponge Dysidea villosa
Author(s) -
HouWen Lin,
BaoHui Cheng,
Guo-Hua Shi,
Guodong Chen,
Bin-Bin Gu,
Yongjun Zhou,
LiLi Hong,
Fan Yang,
Zhiqiang Liu,
Shuqi Qiu,
Zhigang Liu,
PingChang Yang,
Hou-Wen Lin
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-04021-z
Subject(s) - syk , degranulation , sponge , chemistry , stereochemistry , downregulation and upregulation , two dimensional nuclear magnetic resonance spectroscopy , biochemistry , biology , signal transduction , receptor , tyrosine kinase , botany , gene
Four unusual meroterpenoids, dysivillosins A–D ( 1 – 4 ), were isolated from an organic extract of the marine sponge Dysidea villosa collected from the South China Sea. Their planar structures were determined by 1D and 2D NMR and HRESIMS techniques, while the relative and absolute configurations were elucidated by NOESY experiments and comparison between the calculated and experimental ECD spectra. To the best of our knowledge, dysivillosins A–D are the first examples of terpene-polyketide-pyridine hybrid metabolites from the nature. Anti-allergic activity evaluation showed that compounds 1 – 4 potently inhibited the release of β-hexosaminidase, a marker of degranulation, in a dose-dependent manner with IC 50 values of 8.2–19.9 μM. Additionally, the four meroterpenoids could downregulate the production of lipid mediator leukotrienes B 4 (LTB 4 ) and pro-inflammatory cytokine interleukin-4 (IL-4) in the antigen-stimulated RBL-2H3 mast cells. Further biological investigations revealed that dysivillosin A ( 1 ) could suppress the phosphorylation of Syk and PLCγ1 in IgE/FcɛRI/Syk signaling pathway, which resulted in the inhibition of degranulation and the downregulation of LTB 4 and IL-4 production in mast cells.