Discovery of GABA-containing cyclic peptides from the cold-seep-derived fungus Aspergillus unguis SCSIO 41322 for the treatment of inflammatory bowel disease.

Five previously undescribed compounds including three γ-aminobutyric acid (GABA)-containing cyclic peptides, unguisins L-N (1-3), and two diphenyl ethers, aspergillusethers K and L (4 and 5), were isolated from the fungus Aspergillus unguis SCSIO 41322 along with nine known compounds. The planar structures of these undescribed compounds were elucidated based on the combination of HRESIMS and 1D/2D NMR spectroscopic analyses. Furthermore, the absolute configurations of the undescribed cyclic peptides were elucidated by Marfey's method. In terms of bioactivity, compounds 1, 2, and 6 were identified as exhibiting anti-inflammatory activity for the treatment of inflammatory bowel disease (IBD) using a zebrafish wound injury inflammation model, in which 2 showing the greatest efficacy. Further studies demonstrated that 2 might alleviate inflammatory responses in vivo by inhibiting neutrophil recruitment, and effectively inhibits the progression of inflammatory bowel inflammation, exhibiting potential for the treatment of IBD.