Therapeutic strategies that fine-tune epithelial inflammatory responses are highly
sought after in respiratory and mucosal disorders, but few molecules selectively target
these pathways. Vernoniastrum migeodii (S. Moore) Isawumi (Asteraceae) represents
a chemically promising but understudied source of bioactive small molecules. This
study aimed to define the metabolite profile of V. migeodii and evaluate the modulation
of inflammatory epithelial signaling of the constituents. From the methanolic extract
of V. migeodii, five germacranolide sesquiterpenes, vernolide (1), 3′-hydroxylvernolide
(2), pectorolide (3), 4′-hydroxypectorolide-14-O-acetate (4) and 4′-hydroxypectorolide
(5), together with (6S,9R)-vomifoliol (6), eucarvone (7), luteolin (8), and luteolin-7-O-glucoside
(9) were isolated by multiple chromatographic separations. The structures were determined
by comprehensive 1D and 2D NMR spectroscopy. Isolated compounds 1 to 9 together with
previously reported steroids (10–17) and tripeptide (18) were evaluated in LPS-activated
A549 cells by quantitative PCR for interleukin-6 (IL6), interleukin-1β (IL1β), and
prostaglandin-endoperoxide synthase 2 (PTGS2) and by enzyme-linked immunosorbent assay
(ELISA) for IL-6 and IL-8. Compounds 2, 7, steroids 10–17 and aurantiamide acetate
(18) reduced IL6 mRNA relative to the LPS control, while (6S,9R)-vomifoliol (6) increased
IL-6 and elevated IL-8. In the assay IL1β and PTGS2 transcripts were not significantly
altered. These findings highlight the potential of V. migeodii metabolites as modulators
of epithelial inflammatory pathways. Combining chemical and biological evidence provides
a clear basis for structure–activity- and pathway-focused studies.