The Anti-Inflammatory Mechanism of Flaxseed Linusorbs on Lipopolysaccharide-Induced RAW 264.7 Macrophages by Modulating TLR4/NF-κB/MAPK Pathway
Jialong Li, Jing Chen, Ping Huang, Zizhe Cai, Ning Zhang, Yong Wang, Ying Li
Abstract
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-κB/MAPK signaling pathways by targeting the inhibition of activating TLR4 in LPS-induced RAW 264.7 cells. Therefore, the transcription and expression of inflammatory cytokines (i.e., TNF-α, IL-1β, 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-κB/MAPK signaling pathways, suggesting the potential use of food-derived FLs as natural anti-inflammatory supplements in a daily diet.