New Anti-Inflammatory β-Resorcylic Acid Lactones Derived from an Endophytic Fungus, sp.

The endophytic fungus JS0419, isolated from the leaves of the halophyte , produced four new β-resorcylic acid derivatives, colletogloeopyrones A and B ( and ) and colletogloeolactones A and B ( and ), and seven known β-resorcylic acid lactones (RALs). The structures of these compounds were elucidated via analysis of the high-resolution mass spectrometry and nuclear magnetic resonance data. Compounds and showed a dihydrobenzopyranone ring with a linear C9 side chain, which is rarely observed in RALs. All isolated compounds were evaluated for their anti-inflammatory activities. Colletogloeopyrone A (), monocillin II (), and monocillin II glycoside () were effective in reducing nitric oxide production without cytotoxicity. They also inhibited the secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as demonstrated by the expression of mRNA corresponding to IL-6 and TNF-α. Mechanistically, compounds and significantly inhibited the protein expression of nuclear factor-κB, IκBα, IKKα/β, inducible nitric oxide synthase, and cyclooxygenase (COX)-2, whereas compound only inhibited COX-2 expression. This study indicated that RAL-type compounds , , and demonstrated potential anti-inflammatory activity by inhibiting the synthesis of pro-inflammatory cytokines.