Phytochemical and biological studies on rare and endangered plants endemic to China. Part XLVII. Sesquiterpene lactones from the leaves of Michelia opipara and their anti-inflammation effects

Six previously undescribed mono-acetylated sesquiterpene lactones (named opiparolides A‒F, 1–6, resp.), along with five structurally related known compounds, were isolated and characterized from the renewable leaves of the endangered Chinese endemic plant Michelia opipara (family Magnoliaceae) using an LC-MS/MS-based Ion Identity Molecular Networking (IIMN) strategy in combination with conventional chromatographic techniques. The chemical structures and absolute configurations of the compounds were unambiguously determined through comprehensive analyses, including NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), GIAO-based NMR calculations with DP4+ analysis, and electronic circular dichroism (ECD) spectroscopy. Opiparolides A (1) and B (2) were identified as germacrane-type sesquiterpene lactones characterized by a typical α-methylene-γ-lactone moiety, while opiparolides C–F (3–6) are classified as C-15-functionalized eudesmane-type sesquiterpene lactones containing an α,β-unsaturated pentatomic lactone ring. Compounds 1–6 were evaluated for their inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages, exhibiting IC₅₀ values ranging from 8.6 to 16.8 μM. The interactions of sesquiterpene lactones 1 and 6 with the NO signaling pathway were examined through molecular docking studies. Moreover, molecular dynamics simulations further explored the structure and molecular properties of compound 6-iNOS complex. The findings highlight the critical importance of preserving plant species diversity as a reservoir for chemically diverse natural products with potential therapeutic applications in inflammation treatment.