Abstract
Inflammation is the first response of the immune system against bacterial pathogens. This study isolated and examined an antioxidant derived from Lactobacillus fermentation products using cultured media with 1% beet powder. The antioxidant activity of the beet culture media was significantly high. Antioxidant activity-guided purification and repeated sample isolation yielded an isolated compound, which was identified as 5-hydoxymaltol using nuclear magnetic resonance spectrometry. We examined the mechanism of its protective effect on lipopolysaccharide (LPS)-induced inflammation of macrophages. 5-Hydroxymaltol suppressed nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. It also suppressed tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) in the messenger RNA and protein levels in LPS-treated RAW 264.7 cells. Moreover, it suppressed LPS-induced nuclear translocation of NF-κB (p65) and mitogen-activated protein kinase activation. Furthermore, 5-hydroxymaltol reduced LPS-induced reactive oxygen species (ROS) production as well as increased nuclear factor erythroid 2–related factor 2 and heme oxygenase 1 expression. Overall, this study found that 5-hydroxymaltol has anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophage cells based on its inhibition of pro-inflammatory cytokine production depending on the nuclear factor κB signaling pathway, inhibition of LPS-induced reactive oxygen species production, inhibition of LPS-induced mitogen-activated protein kinase induction, and induction of the nuclear factor erythroid 2–related factor 2/heme oxygenase 1 signaling pathway. Our data showed that 5-hydroxymaltol may be an effective compound for treating inflammation-mediated diseases.
Highlights
Innate, or nonspecific immune response is the first barrier against invading detrimental particles and organisms, and it involves macrophage and inflammatory biomolecules [1].Inflammation occurs in all human tissue and has a protective effect against extrinsic pathogens and intrinsic injuries [2]
This study examined the ability of 5-hydroxymaltol to suppress the nuclear translocation of nuclear factor κB (NF-κB)
We examined cytosolic inhibitor κB (IκB), which is a regulator of NF-κB. 5-Hydroxymaltol pretreatment blocked the downregulation of IκB-α in LPS-treated cells
Summary
Nonspecific immune response is the first barrier against invading detrimental particles and organisms, and it involves macrophage and inflammatory biomolecules [1].Inflammation occurs in all human tissue and has a protective effect against extrinsic pathogens and intrinsic injuries [2]. Antioxidants 2021, 10, 1324 materials and dead cells as well as respond to various infection signals [4] They have toll-like receptors that serve as a first-line host defense against infection [4,5]. Lipopolysaccharides (LPSs) are major components of the cell wall of gram-negative bacteria and induce strong cellular signals of macrophages in the innate immune system [5,6]. They activate macrophages by binding toll-like receptor 4 and stimulate several intracellular signaling pathways, including the nuclear factor κB (NF-κB) pathway and three mitogen-activated protein kinase (MAPK) pathways, namely, extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNKs)/stress-activated protein kinases, and p38 MAPK [7,8]
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