New Oligophenalenone Dimers from Talaromyces stipitatus with Potential Anti-Neuroinflammatory Activity

Five new oligophenalenone dimers, talarostipins A-E (1-5), including four N-containing derivatives, together with sixteen known duclauxin analogues (6-21), were isolated from the soil fungus Talaromyces stipitatus, and their structures were identified by a combination of NMR spectroscopic analyses, HRESIMS and ECD spectra. Anti-neuroinflammatory activity evaluation indicated that duclauxamide C (8) significantly inhibited NO generation in lipopolysaccharide (LPS)-induced BV-2 microglial cells with an IC₅₀ value of 5.0 ± 0.7 μM. Transcriptome sequencing analysis indicated that 8 probably suppressed neuroinflammation by targeting the NF-κB signaling pathway. Further verification was conducted by Western blot analysis, which indicated that 8 exerted its anti-neuroinflammatory effect by downregulating the expression of pro-inflammatory proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and p65.