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Casein glycomacropeptide hydrolysates inhibit PGE2 production and COX2 expression in LPS-stimulated RAW 264.7 macrophage cells via Akt mediated NF-κB and MAPK pathways

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Abstract

A casein glycomacropeptide hydrolysate (GMPH) was found to possess inhibitory activity against lipopolysaccharide (LPS)-induced inflammatory response in our previous study. In the current study, the inhibitory effect and the underlying molecular mechanism of GMPH on inflammatory response in LPS-stimulated RAW264.7 macrophages were further investigated. Results showed that GMPH significantly suppressed LPS-induced intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production. GMPH reduced the production of prostaglandin E2 (PEG2) and the expression of cyclooxygenase-2 (COX-2) and cytosolic phospholipase A2 (cPLA2) in LPS-stimulated macrophages. GMPH also attenuated LPS-induced phosphorylation of MAPK (c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38) and protein kinase B (Akt). Furthermore, GMPH inhibited nuclear transcription factor kappa-B (NF-κB) activation by suppressing the nuclear translocation of NF-κB p65, which was markedly reversed by LY294002, an Akt inhibitor. These results demonstrated that GMPH exerts anti-inflammatory functions through the inactivation of MAPK and Akt in LPS-stimulated RAW264.7 macrophages, therefore may hold potential to ameliorate inflammation-related metabolic disorders.

Graphical abstract: Casein glycomacropeptide hydrolysates inhibit PGE2 production and COX2 expression in LPS-stimulated RAW 264.7 macrophage cells via Akt mediated NF-κB and MAPK pathways

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Publication details

The article was received on 18 Dec 2017, accepted on 25 Feb 2018 and first published on 27 Mar 2018


Article type: Paper
DOI: 10.1039/C7FO01989K
Citation: Food Funct., 2018, Advance Article
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    Casein glycomacropeptide hydrolysates inhibit PGE2 production and COX2 expression in LPS-stimulated RAW 264.7 macrophage cells via Akt mediated NF-κB and MAPK pathways

    T. Li, D. Gao, M. Du, X. Cheng and X. Mao, Food Funct., 2018, Advance Article , DOI: 10.1039/C7FO01989K

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