A multifunctional alanine-rich anti-inflammatory peptide BCP61 showed potent inhibitory effects by inhibiting both NF-κB and MAPK expression

Abstract

The purified BCP61 was reported to be a unique low-molecular-weight (MW) anti-microbial peptide because of its non-identical alanine-rich N-terminal sequence. In this study, we investigated the anti-inflammatory effects of BCP61 on induction of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. The treatment with BCP61, with varying concentrations of 10, 50, and 100 μg/mL, inhibited levels of expression of LPS-induced NF-κB and MAPKs (extracellular signal-related kinases (ERKs), c-Jun NH-terminal kinase (JNK), and mitogen-activated protein (p38)) as well as production of pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). The results suggested that BCP61 prevents inhibitor of kappa B (IκBα) phosphorylation and degradation, thereby inhibiting the nuclear translocation of the p65 protein. We do report that the use of BCP61 in the treatment of inflammation as well as microbial infection could be a potent therapeutic candidate.

Fucoidan Isolated from Saccharina japonica Inhibits LPS-Induced Inflammation in Macrophages via Blocking NF-κB, MAPK and JAK-STAT Pathways

“…As reported that the activities of p38 and JNK MAPKs are significantly increased in macrophages stimulated by LPS through enhancing their phosphorylation levels, and then accelerate inflammatory process [42,46]. In addition, ERK1/2 is identified to be directly related to NF-κB activation [44]. The present study displayed that the increased phosphorylation levels of ERK1/2, JNK, and p38 MAPKs were effectively suppressed by SF6 treatment.…”

“…Generally, NF-κB, localizing in the cytoplasm, presents as a complex with IκB in an inactive form. Upon inflammatory activation, the upstream kinase IKK mediates the phosphorylation and degradation of IκB, which leads to the release and translocation of NF-κB into the nucleus and results in the inflammatory genes transcription [7,44,45]. In our study, the effect of SF6 on NF-κB signal pathway was examined; the result indicated the phosphorylation level of NF-κB in the nucleus was remarkably increased by LPS stimulation, but nevertheless, pre-treatment with SF6 effectively inhibited the translocation of NF-κB into the nucleus.…”

Ginkgo biloba sarcotesta polysaccharide inhibits inflammatory responses through suppressing both NF‐κB and MAPK signaling pathway

“…As an endogenously produced gas, NO serves as a key signal transduction molecule and plays a key role in the inflammatory response. As a bioactive lipid, PGE 2 is involved in the initiation of numerous inflammatory responses . To investigate whether GBSP3a inhibits the LPS‐induced inflammatory response, production of the inflammatory mediators (NO and PGE 2 ) was determined.…”

“…Similar to NF‐κB, mitogen‐activating protein kinases (MAPKs) is another essential signaling pathway involved in the regulation of the expression of pro‐inflammatory cytokines during the inflammatory process . In LPS‐stimulated macrophages, three major MAPK families, namely the extracellular signal‐regulated kinases (ERK1/2), mitogen‐activated protein (MAP p38) and c‐Jun N‐terminal kinase (JNK), are activated, and ultimately regulate the expression of pro‐inflammatory genes through phosphorylating transcription factors including NF‐κB . Accordingly, blocking either the NF‐κB signaling pathway or MAPK pathway, or both, are promising strategies for the effective control of inflammation.…”

“…Inflammation, a process that is essential for homeostasis and fine regulation, is a complex pathological protective response to tissue injuries, infection, stress or other stimuli . Adequate inflammatory response can allow people to avoid severe tissue damage, but excessive inflammation is potentially dangerous to host organisms.…”