Anti-Inflammatory Activity of Monoterpene Phenol Dimers from Satureja bachtiarica.

Satureja bachtiarica (Bakhtiari savory) is an aromatic herb cultivated both as a culinary spice and for its medicinal uses. Species of Satureja are known to exhibit anti-inflammatory properties. Monoterpene phenol dimers with biphenyl skeletons have been identified in these plants and structural investigations revealed the key role of the biphenyl scaffold in interacting with MAPEG family proteins. Thus, in the present contribution, we investigated by biochemical and cell-based assays, together with molecular docking and molecular dynamics investigations, the modulation of inflammatory mediators of three isolated monoterpene phenol dimers (1-3). Molecular modeling and in vitro enzymatic assays of 1-3 against soluble epoxide hydrolase (sEH) and 5-lipoxygenase (5-LOX) identified the structural elements accountable for binding vs the biological targets. Unlike 2 and 3, in vitro experiments revealed that 1 did not show cytotoxicity. Interestingly, 1 selectively alters the profile of AA-derived mediators produced by LPS-activated macrophages, suppressing both IL-6 and PGE2. The obtained results revealed how compound 1 may not only suppress inflammation but also promote the active resolution of inflammatory responses and, by integrating computational analysis, provide clues to design more effective analogues.