Miasporone (1), a new diterpenoid featuring a 6/7/5-fused tricyclic skeleton, was isolated from the deep-sea-derived fungus Microascus algicola C7-37M2. Its planar structure and absolute configuration were elucidated by spectroscopic analysis combined with GIAO/DP4+ NMR and TDDFT-ECD calculations. Miasporone dose-dependently reversed lipopolysaccharide (LPS)-induced M1 macrophage polarization by suppressing nitric oxide (NO) production, scavenging mitochondrial reactive oxygen species (ROS), and downregulating NLRP3 expression without appreciable cytotoxicity. Consistent with its in vitro efficacy, miasporone exhibited potent anti-inflammatory and analgesic activities in a Complete Freund's Adjuvant-induced mouse model, attenuating hyperalgesia, restoring gait coordination, and alleviating paw hyperemia, with efficacy comparable to that of dexamethasone. These findings highlight miasporone as a structurally distinctive fungal diterpenoid and a promising lead for anti-inflammatory and analgesic drug development.
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