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

ABSTRACT

Two previously undescribed highly oxygenated monoterpenes, (1 R ,2 S ,5 R )‐3‐ p ‐menthen‐1,2,5‐triol (1) and (1 R ,5 S )‐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 IC ₅₀ values of 14.5 and 17.4 µM, respectively. The remaining compounds displayed moderate inhibitory effects, with IC ₅₀ 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.