The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis

Cembranolides are characteristic metabolites in marine
soft corals,
with complex structures and widespread biological activities. However,
seldom has an intensive pharmacological study been done for these
intriguing marine natural products. In this work, systematic chemical
investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART),
resulting in the isolation and identification of 31 cembrane-type
diterpenoids, including six new ones. In the bioassay, several compounds
showed significant anti-inflammatory activities on the inhibition
of NO production. The structure–activity relationship (SAR)
was comprehensively analyzed, and two most bioactive and less toxic
compounds 8 and 9 could inhibit inflammation
through suppressing NF-κB and MAPK signaling pathways, and reduce
the secretion of inflammatory cytokines. In a mouse model of dextran
sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability
to repair the colon epithelium, giving insight into the application
of cembranolides as potential ulcerative colitis (UC) agents.