Bioactive pulvinones from a marine algicolous fungus Aspergillus terreus NTU243

Marine fungi are regarded as an under-explored source of structurally interesting and bioactive natural products with the potential to provide attractive lead compounds for drug discovery. In this study, several fungal strains were isolated from marine algae collected from the northeastern coast of Taiwan. In the preliminary antimicrobial screening against bacteria and fungi, the ethyl acetate extract of the fermented products of Aspergillus terreus NTU243 derived from a green alga Ulva lactuca was found to exhibit significant antimicrobial activities. Therefore, bioassay-guided separations of the active principle from liquid and solid fermented products of A. terreus NTU243 were undertaken, which resulted in the isolation and purification of 16 compounds. Their structures were elucidated by spectroscopic analysis to be four previously undescribed aspulvinones S-V as well as twelve known compounds. All the isolates were assessed for anti-inflammatory activity by measuring the amount of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 cells, and aspulvinone V, butyrolactone I, and (+)-terrein inhibited 45.0%, 34.5%, and 49.2% of NO production, respectively, at 10 μM concentration. Additionally, zymography showed that the conditioned medium of THP-1 cells post-LPS challenged significantly enhanced matrix metalloproteinase (MMP)-9-mediated gelatinolysis, and pretreatment with aspulvinones U and V significantly attenuated MMP-9-mediated gelatinolysis by 56.0% and 67.8%, separately.