Discovery of anti-inflammatory agents from Oreorchis patens, a medicinal and edible plant: mechanistic insights and potential therapeutic applications.

Bioactive dietary compounds serve as beneficial supplements for managing chronic inflammation, and plants with both edible and medicinal properties represent a safe and effective source of these compounds. In this study, metabolomic investigation of the edible parts of Oreorchis patens, a plant classified in China as having food and medicine homology, led to the identification of six phenanthrene derivatives, including two monomers and four dimers. Their planar structures and absolute configurations were established by nuclear magnetic resonance spectroscopy and electronic circular dichroism, supported by computational chemistry analyses. Among these compounds, phenanthrene dimer 3 exhibited notable anti-inflammatory activity in lipopolysaccharide-stimulated murine alveolar (MH-S) macrophages. More importantly, compound 3 was found to stably bind to the allosteric drug and metabolite site of adenosine monophosphate-activated protein kinase (AMPK), thereby protecting the kinase from dephosphorylation and promoting its activation. Activated AMPK was subsequently shown to regulate NF-κB signaling, resulting in pronounced anti-inflammatory effects. Collectively, these findings reveal nutritionally valuable bioactive compounds from a food and medicine homologous plant that act as AMPK modulators with anti-inflammatory potential.