Discovery of anti-inflammatory pyrrole alkaloids from Curvularia lunata CL1.

Two novel pyrrole alkaloids, pyrinoids A (1) and B (2), were isolated from the culture of Curvularia lunata CL1. Their structures were elucidated using extensive spectroscopic methods, including NMR, HRESIMS, IR, and UV, alongside electronic circular dichroism (ECD) analysis for absolute configuration determination. Both compounds exhibited significant inhibitory activity against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW264.7 cells, with IC50 values of 14.06 ± 0.74 and 12.64 ± 3.82 μM, respectively. Additionally, pyrinoids A and B enhanced the secretion of the anti-inflammatory cytokine IL-10 and suppressed pro-inflammatory mediators IL-6 and PGE2. They also modulated the transcription levels of key inflammatory markers, downregulating IL-6 and iNOS while upregulating IL-10 expression. These findings suggest that pyrinoids A and B possess promising potential as anti-inflammatory agents for mitigating inflammation in macrophage-mediated pathways.