Phenanthrene derivatives from Pinalia globulifera with anti-inflammatory activity in LPS-stimulated RAW264.7 macrophages

Phytochemical investigation of the whole plant of Pinalia globulifera afforded 26 compounds, including one new natural product, pinaglobin A (1), previously known only from synthesis; nine previously undescribed compounds, pinaglobins B–J (2–10); and sixteen known compounds (11–26). Structures of previously undescribed compounds were established by spectroscopic analysis, and their stereochemistry was determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. Several compounds (compounds 1 − 2, 6, and 11−21) were evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, showing significant suppression of nitric oxide (NO) production without notable cytotoxicity. Among them, nudol (11) exhibited the strongest inhibitory effect, markedly downregulating nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) expression. These findings indicate that the anti-inflammatory activity of P. globulifera isolates is mediated mainly through the NF-κB/iNOS/NO signaling pathway, highlighting its phenanthrene derivatives as promising leads for anti-inflammatory drug development.