Berkeleyacetal C, a meroterpenoid isolated from the fungus Penicillium purpurogenum MHZ 111, exerts anti-inflammatory effects via inhibiting NF-κB, ERK1/2 and IRF3 signaling pathways

Berkeleyacetal C (BAC), a meroterpenoid compound, was isolated from the fungus Penicillium purpurogenum MHZ 111 and showed favorable activity of inhibiting nitrogen oxide (NO) production of macrophages stimulated by lipopolysaccharide (LPS) in our preliminary screening. In order to develop novel therapeutic drug for acute and chronic inflammatory diseases, the anti-inflammatory activity and underlying mechanisms of BAC were investigated in macrophages and neutrophils. The results showed that BAC significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and the following NO production by macrophages. The expression and secretion of key pro-inflammatory factors and chemokines, including tumor necrosis factor-alpha (TNF-alpha), inter-leukin- 6 (IL-6), interleukin-1 beta (IL-1 beta), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and monocyte chemotactic protein-1 (MCP-1) were also intensively suppressed by BAC. Furthermore, BAC also markedly inhibited activation of neutrophils and reactive oxygen species production. In mechanism study, BAC selectively suppressed phosphorylation of nuclear factor-kappa B (NF-kappa B), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and interferon regulatory transcription factor 3 (IRF3) during the activation of NF-kappa B, mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 1 and 3 (STAT1/3), and IRF3 signaling pathways induced by LPS. In summary, BAC exerts strong anti-inflammatory effects by inhibiting NF-kappa B, ERK1/2 and IRF3 signaling pathways and thereby shows great potential to be developed into therapeutic agent for inflammatory disorders.