Exploring Chemical Composition of the Aerial Parts of Vernoniastrum migeodii and Anti-Inflammatory Activity of the Compounds

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