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

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.