The Anti-Inflammatory Mechanism of Flaxseed Linusorbs on Lipopolysaccharide-Induced RAW 264.7 Macrophages by Modulating TLR4/NF-κB/MAPK Pathway

Flaxseed linusorbs (FLs), cyclic peptides derived from flaxseed oils, have shown multiple activities such as anticancer, antibacterial, and anti-inflammatory effects. However, the anti-inflammatory monomers of FLs and their mechanisms are still unclear. In this study, we have elucidated that FLs suppress the modulation of NF-kappa B/MAPK signaling pathways by targeting the inhibition of activating TLR4 in LPS-induced RAW264.7 cells. Therefore, the transcription and expression of inflammatory cytokines (i.e., TNF-alpha, IL-1 beta, and IL-6) and inflammatory mediator proteins (i.e., iNos and Cox-2) were significantly suppressed by FLs. In addition, an in silico study discovered that eight monomers of FLs showed high-affinity bindings with TLR4. In silico data combined with HPLC results indicated that FLA and FLE, accounting for 44%, were likely the major anti-inflammatory monomers in FLs. In summary, FLA and FLE were proposed as the main anti-inflammatory active cyclopeptides via hindering TLR4/NF-kappa B/MAPK signaling pathways, suggesting the potential use of food-derived FLs as natural anti-inflammatory supplements in a daily diet.

Automated summary

Flaxseed linusorbs (FLs), cyclic peptides derived from flaxseed oils, have been found to have anti-cancer, antibacterial, and anti-inflammatory effects. This study discovered that FLs suppress the NF-kappa B/MAPK signaling pathways by targeting TLR4, leading to the inhibition of inflammatory cytokines and mediator proteins. In silico data and HPLC results indicate that FLA and FLE are the major anti-inflammatory monomers in FLs. These findings suggest that FLs derived from food sources could be used as natural anti-inflammatory supplements in daily diet.