The pepsinolytic hydrolysate from Johnius belengerii frame inhibited LPS-stimulated production of pro-inflammatory mediators via the inactivating of JNK and NF-κB pathways in RAW 264.7 macrophages

Abstract

The objective of this study was to investigate the anti-inflammatory effects of the pepsinolytic hydrolysate from the fish frame, Johnius belengerii, on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The J. belengerii frame hydrolysate (JFH) significantly suppressed nitric oxide (NO) secretion on LPS-stimulated RAW264.7 macrophages. Moreover, the JFH markedly inhibited the levels of protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the LPS-stimulated mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 was downregulated when cells were cultured with the JFH. The JFH significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK) and the translocation of nuclear factor-kappa B (NF-κB) in macrophages. As the result, the JFH has the potential antiinflammatory activity via blocking the JNK and NF-κB signal pathways.

Impact of the Plastein Reaction of Casein Hydrolysates in the Presence of Exogenous Amino Acids on Their Anti-Inflammatory Effect in the Lipopolysaccharide-Stimulated Macrophages

“…For example, the polysaccharides have been elucidated to inhibit cellular production of pro-inflammatory mediators through inhibition of NF-κB signaling pathway and reduction in p65 nuclear translocation [ 46 , 47 ]; for example, the garlic extract could reduce the production of NO in the LPS-stimulated RAW264.7 macrophages by inhibiting NF-κB nuclear translocation and HO-1 activation [ 48 ]. In addition, the fishbone protein hydrolysates showed an anti-inflammatory effect on the RAW264.7 macrophages by down-regulating the phosphorylation levels of JNK and NF-κB, resulting in a block in JNK/NF-κB signaling pathways [ 21 ], while lactoferrin could combat against the LPS-induced inflammation in human nasal epithelial cells via inhibition on MEK1/2-MAPK signaling pathway [ 49 ]. Overall, the TLR4/MyD88/NF-κB signaling pathway has attracted widespread attention in the scientific community due to their implant-related innate immune recognition and immuno-modulation [ 50 , 51 ].…”

“…Several bioactive components were reported to mediate the expression of the targeted genes and related proteins in the NF-κB signaling pathway or mediate the expression of several inflammatory cytokines regulating the NF-κB signaling pathway or those suppressing excessive inflammatory responses [ 18 , 19 , 20 ]. For example, the hydrolysates from fish and rice proteins could inhibit NF-κB activation, reduce p65 translocation to the nucleus, block NF-κB signaling pathway, and exert anti-inflammatory function [ 21 , 22 ]. Therefore, the question of whether the plastein reaction (especially that occurs in the presence of exogenous amino acids) can change the anti-inflammatory effect of casein hydrolysates attracts our attention.…”

A phlorotannins‐loaded homogeneous acellular matrix film modulates post‐implantation inflammatory responses

“…In this study, we investigated in vitro anti‐inflammatory activity using RAW 264.7 macrophage, commonly used as an appropriate macrophage model and to detect cytotoxicity (Choi et al., 2018; Heo et al., 2018; Kim et al., 2018). Moreover, LPS is an endotoxin that presented in the outer membrane of gram‐negative bacteria, such as Escherichia coli , Pseudomonas aeruginosa , and Klebsiella pneumoniae , and is used as a central inflammatory stimulator on several cell lines (Kim et al., 2018).…”

“…Moreover, LPS is an endotoxin that presented in the outer membrane of gram‐negative bacteria, such as Escherichia coli , Pseudomonas aeruginosa , and Klebsiella pneumoniae , and is used as a central inflammatory stimulator on several cell lines (Kim et al., 2018). Furthermore, LPS triggers macrophage activation and production of inflammatory mediators such as iNOS, COX‐2, nitric oxide (NO), and prostaglandin E 2 (PGE 2 ) (Heo et al., 2018; Nguyen et al., 2016). iNOS is an important inflammatory mediator expressed in various cells and tissues and produces NO (Ren et al., 2020).…”

Comparative Evaluation of Forsythiae Fructus From Different Harvest Seasons and Regions by HPLC/NIR Analysis and Anti-inflammatory and Antioxidant Assays

“…Previous studies have shown that FF is widely used to treat lipopolysaccharide (LPS)-induced inflammation and oxidation ( Lee et al, 2018 ; Shao et al, 2021 ). In response to LPS, macrophages produce NO, which is synthesized by iNOS, increasing the level of nuclear NF-κB as well as pro-inflammatory cytokines such as TNF-α, IL-1β ( Heo et al, 2018 ; Hung et al, 2019 ). It also activates the Nrf2 signaling pathway, resulting in the secretion of antioxidant enzymes such as HO-1 and NQO1 ( Lim et al, 2020 ).…”