Chartarlactams U-X: Novel Phenylspirodrimanes from a Marine Derived Fungus Stachybotrys sp. SZU-W23 with Anti-Inflammatory Activity Mediated by the NF-κB/ROS Signaling Pathways

In this investigation, the anti-inflammatory potential of phenylspirodrimanes (PSDs) produced by the marine-derived fungal strain <i>Stachybotrys</i> sp. SZU-W23 was systematically explored. A total of 15 PSDs were successfully isolated. Among them, four novel compounds, designated as chartarlactams U-X, were precisely characterized using NMR, HRESIMS, and ECD analyses. Specifically, compound <b>10</b> exhibited the most potent inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 macrophages within the 0.3-30 μM concentration range, with an IC₅₀ value of 12.4 μM. Additionally, MTT assays revealed no detectable cytotoxicity at these concentrations. Mechanistic studies revealed that compound <b>10</b> effectively suppressed ROS generation, likely inactivating the NF-κB signaling pathway and consequently downregulating pro-inflammatory mediators, including iNOS, IL-6, and IL-1β.