Novel Fatty Acid In Cordyceps Suppresses Influenza A (H1n1) Virus-Induced Proinflammatory Response Through Regulating Innate Signaling Pathways

Influenza virus (IV) infections usually cause acute lung injury characterized by exaggerated proinflammatory responses. The paucity of therapeutic strategies that target host immune response to attenuate lung injury poses a substantial challenge in management of IV infections. In this study, we chemically synthesized a novel fatty acid (2Z,4E)-deca-2,4-dienoic acid (DDEA) identified from Chinese Cordyceps by using UHPLC-Q : TOF-MS techniques. The DDEA did not inhibit H1N1 virus replication but attenuated proinflammatory responses by reducing mRNA and protein levels of TNF-alpha, IFN-alpha, IFN-beta, IL-6, CXCL-8/IL-8, CCL-2/MCP-1, CXCL-10/IP-10, CCL-3/MIP-1 alpha, and CCL-4/MIP-1 beta in A549 cells and U937-derived macrophages. The anti-inflammatory effect occurred through downregulations of TLR-3-, RIG-I-, and type I IFN-activated innate immune signaling pathways. Altogether, our results indicate that DDEA may potentially be used as an anti-inflammatory therapy for the treatment of IV infections.