Unprecedented Meroterpenoids Exert Anti-inflammatory Activity by Targeting NF-κB and PI3K Signaling Pathways

Four classes of unprecedented meroterpenoids (1–10), together with 10 new analogues, were isolated from the symbiotic fungi biotransformation extract. Among them, compounds 1–3 were characterized as the inaugural meroterpenoids containing a 5/3/6/6/6 fused carbon ring system. Compounds 4 and 5 were identified as the first meroterpenoids featuring the rare 6/6/6/6 tetracyclic carbon skeleton. Compound 6 stood out as the first meroterpenoid exhibiting a novel 5/3/6/6/5 pentacyclic framework. Notably, compounds 7–10 were reported as a novel 6/6/6/5 carbon skeleton architecture. Furthermore, 1 and 6 showed stronger inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells with IC50 values of 7.46 and 6.02 μM, respectively, than the positive control (indomethacin, IC50 = 31.17 μM). Meanwhile, 1 and 6 significantly downregulated the expression of inflammatory enzyme iNOS and also inhibited the phosphorylation of NF-κB, PI3K, and IκB-α in a concentration-dependent manner.