5-Hydroxymaltol Derived from Beetroot Juice through Lactobacillus Fermentation Suppresses Inflammatory Effect and Oxidant Stress via Regulating NF-kB, MAPKs Pathway and NRF2/HO-1 Expression

• Published in: Antioxidants 2021-08, Vol.10 (8), p.1324
• Main Authors: Kim, Su-Lim, Choi, Hack Sun, Ko, Yu-Chan, Yun, Bong-Sik, Lee, Dong-Sun
• Format: Article
• Language: English
• Subjects: 5-hydroxymaltol; Acids; Antioxidants; Bacteria; Carbon; Cell culture; Chromatography; Culture media; cytokines; Fermentation; Heme; Immune system; Inflammation; Kinases; Lactobacillus; Lactobacillus fermentation; lipopolysaccharide; Lipopolysaccharides; Macrophages; MAP kinase; Molecular structure; mRNA; NF-κB protein; Nitric oxide; Nitric-oxide synthase; NMR; Nrf-2; Nuclear magnetic resonance; Nuclear transport; Oxidants; Oxidative stress; Oxygenase; Protein kinase; Reactive oxygen species; Signal transduction; Solvents; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox10081324

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.