Anti-Helicobacter pylori and Anti-Inflammatory Sesquiterpenoids from the Rhizoma of Atractylodes macrocephala

<i>Helicobacter pylori</i>, a spiral-shaped bacterium found in the stomach, is associated with various gastrointestinal and systemic health conditions. Effective suppression of <i>H. pylori</i> is therefore critical for managing gastrointestinal diseases. In a search for natural products with anti-<i>H. pylori</i> activity, the extract of <i>Atractylodes macrocephala</i> rhizoma showed significant inhibitory effects. Chromatographic purification of <i>A. macrocephala</i> extract yielded thirteen compounds, which were identified as ten sesquiterpenes and three polyacetylenes by spectroscopic analysis. The sesquiterpene compounds belong to the eudesmane or eudesmane lactone types and exhibited structure-dependent efficacy. The major eudesmane lactone sesquiterpene, atractylenolide I (<b>1</b>), showed strong inhibitory activity comparable to metronidazole, a positive control, and atractylenolide III (<b>3</b>) also showed good efficacy. However, structural modification such as hydroxylation, methylation, or acetylation of the sesquiterpenes led to reduced activity. In contrast, polyacetylene derivatives displayed only mild inhibitory effects. Further evaluation of the active compounds against three <i>H. pylori</i> strains such as 51, 43504, and 26695 showed that atractylenolide I (<b>1</b>) had potent inhibitory effects against all three strains, with MIC₅₀ values of ranging from 27.3 to 48.6 μM and MIC₉₀ values from 45.4 to 87.2 μM. Atractylenolide III (<b>3</b>) exhibited selective activity against strain 51 with MIC₅₀ value of 89.9 μM. Both compounds also exhibited anti-inflammatory activity with IC₉₀ values of 23.3 and 31.1 μM, respectively, although they showed little effect on urease. This is the first report on the anti-<i>H. pylori</i> efficacy of various constituents of <i>A. macrocephala</i> and comparative analysis of inhibitory effects against several strains, which will provide scientific evidence supporting its potential as therapeutic agent for <i>H. pylori</i>-related infection.