Two New Highly Oxygenated Monoterpenes From the Seeds of Dysphania ambrosioides and Their Inflammatory Activity In...

Two previously undescribed highly oxygenated monoterpenes, (1R,2S,5R)-3-p-menthen-1,2,5-triol (1) and (1R,5S)-2-oxo-3-p-menthen-1,5-diol (2), together with five known monoterpenes (3-7), were isolated from the seeds of Dysphania ambrosioides. Their chemical structures were determined using various spectroscopic analyses (HRESIMS, and 1D and 2D NMR). The absolute configurations of compounds 1 and 2 were successfully established by both experimental and calculated ECD spectra using TD-DFT methods. Among the isolates, compounds 3 and 6 exhibited significant inhibitory activity against NO production in LPS-stimulated RAW264.7 cells, with IC₅₀ values of 14.5 and 17.4 µM, respectively. The remaining compounds displayed moderate inhibitory effects, with IC₅₀ values ranging from 42.1 to 58.2 µM. Molecular docking studies suggested that compounds 1-7, as monoterpene derivatives, are promising iNOS inhibitors rather than inhibitors of TNF-α, COX-2, or IL-6 inflammatory cytokines.