An abietane diterpenoid from Tripterygium wilfordii inhibits influenza A virus replication and modulates host immunity

Influenza A virus (IAV) infection remains a pervasive global public health threat. Natural products are recognised as a valuable reservoir for the discovery and development of novel antiviral agents. This study investigated the anti-IAV activity and mechanisms of 11-Hydroxy-14-methoxy-18 (4→3)-abeo-abieta-3,8,11,13- tetraen-18-oic acid named Triptobenzene H (TPZH), a diterpenoid isolated from Tripterygium wilfordii. In IAV-infected MDCK cells, TPZH increased the viability of IAV-infected MDCK cells, limited ROS accumulation, and alleviated mitochondrial dysfunction. Mechanistically, TPZH targeted the viral replication stage, disrupting the IAV life cycle and reducing viral loads. Furthermore, in virus-stimulated macrophages, TPZH suppressed inflammatory protein expression and cytokine overproduction through inhibiting activation of MAPK and NF-κB signalling pathways. Collectively, TPZH exerts anti-influenza effects by blocking viral replication and alleviating virus-mediated inflammatory injury via modulation of macrophage-dependent immune responses. This study demonstrates that TPZH exhibits multi-target pharmacological properties and holds promising therapeutic potential for anti-influenza treatment.