Flaxseed orbitides, linusorbs, inhibit LPS-induced THP-1 macrophage inflammation

Linusorbs (flaxseed orbitides) are a family of naturally-occurring cyclic peptides. Previously, we reported that their anticancer effects were associated with their structures. In this study, we investigated the anti-inflammatory activities of 2 different linusorbs ([1-9-N alpha C]-linusorb B2 and [1-9-N alpha C]-linusorb B3) in lipopolysaccharide (LPS)-induced THP-1 macrophage activation as well as the underlying mechanism of this inflammatory response. Both molecules suppressed pro-inflammatory mediators (TNF-alpha, IL-1 beta, IL-6, NO and COX-2) and were involved in downregulating the NF-kappa B signaling pathway. The suppressive effects on pro-inflammatory mediators were comparable and the concentration range of action was similar (1-4 mu M). However, the concentration of compound that induced downregulation of the NF-kappa B pathway was different for each compound. While [1-9-N alpha C]-linusorb B3 could inhibit the activation of the NF-kappa B pathway at concentrations of 1 and 2 mu M, [1-9-N alpha C]-linusorb B2 induced a comparable inhibitory effect at a concentration of 4 mu M.