Triterpenoids From Ilex rotunda and Their Anti-Inflammatory Effects by Interfering With NF-κB and MAPK Activation.

Ilex rotunda is traditionally employed to treat inflammatory diseases. A feature-based molecular network guided the phytochemical investigation of this plant, which resulted in the isolation and identification of two new and nine known compounds. Through the analysis of their mass and spectroscopic data and comparison with those published in the literature, their structures were determined. The isolated compounds were discovered to have anti-inflammatory properties that suppressed the synthesis of nitric oxide mediators and inflammatory cytokines (tumor necrosis factor-α [TNF-α] production and interleukin-6 [IL-6]). Compound 1 and the new compounds 3 and 6 downregulated the expression levels of the COX-2 and iNOS enzymatic proteins. Furthermore, compounds 3 and 6 were mechanically found to downregulate LPS-stimulated inflammation via NF-κB and MAPK inactivation by inhibiting the nuclear translocation of p65 and preventing the phosphorylation of Iκαβ and ERK kinases. The molecular docking data on binding affinity and interactions with active compounds docked into the targeted proteins supported the above anti-inflammatory effects. We identified the active constituents of I. rotunda that possess anti-inflammatory properties, aiming to develop strategies for treating inflammation.