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

Abstract

The endophytic fungus Colletotrichum gloeosprioides JS0419, isolated from the leaves of the halophyte Suaeda japonica, produced four new beta-resorcylic acid derivatives, colletogloeopyrones A and B (1 and 2) and colletogloeolactones A and B (3 and 4), and seven known beta-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 1 and 2 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 (1), monocillin II (5), and monocillin II glycoside (6) were effective in reducing nitric oxide production without cytotoxicity. They also inhibited the secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as demonstrated by the expression of mRNA corresponding to IL-6 and TNF-alpha. Mechanistically, compounds 5 and 6 significantly inhibited the protein expression of nuclear factor-kappa B, I kappa B alpha, IKK alpha/beta, inducible nitric oxide synthase, and cyclooxygenase (COX)-2, whereas compound 1 only inhibited COX-2 expression. This study indicated that RAL-type compounds 1, 5, and 6 demonstrated potential anti-inflammatory activity by inhibiting the synthesis of pro-inflammatory cytokines.