Anti-inflammatory Effects of Dielectric Barrier Discharge Plasma Induced Phloridzin against Lipopolysaccharide-stimulated RAW 264.7 Macrophages
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Phloridzin (1), a natural dihydrochalcone, has been extensively studied for its antioxidant and antidiabetic properties. In this study, we investigated the anti-inflammatory effects of three plasma-induced phloridzinderivatives such as deglucosyl-methylene-bis-phloridzin (2), methylene-bis-phloridzin (3), and phloretin (4) inlipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Cells were treated with various concentrations(12.5, 25, 50, and 100 μM) of compounds 1–4. Among them deglucosyl-methylene-bis-phloridzin (2) was identifiedas the most potent derivative, significantly inhibiting nitric oxide (NO) production without any cytotoxicity. Furthermore, western blot analysis showed that compound 2 strongly suppressed the expression of inducible nitricoxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It also decreased the secretion of pro-inflammatory cytokines,including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Additionally, compound 2 also markedlyreduced intracellular reactive oxygen species (ROS) generation in a dose-dependent manner, as confirmed byDCFDA fluorescence assay, and DPPH radical scavenging activity. These results indicate that deglucosyl-methylenebis-phloridzin (2) may be used as an effective anti-inflammatory and antioxidant agent for the prevention or treatmentof inflammatory diseases.
Abstract
Phloridzin (1), a natural dihydrochalcone, has been extensively studied for its antioxidant and antidiabetic properties. In this study, we investigated the anti-inflammatory effects of three plasma-induced phloridzinderivatives such as deglucosyl-methylene-bis-phloridzin (2), methylene-bis-phloridzin (3), and phloretin (4) inlipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Cells were treated with various concentrations(12.5, 25, 50, and 100 μM) of compounds 1–4. Among them deglucosyl-methylene-bis-phloridzin (2) was identifiedas the most potent derivative, significantly inhibiting nitric oxide (NO) production without any cytotoxicity. Furthermore, western blot analysis showed that compound 2 strongly suppressed the expression of inducible nitricoxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It also decreased the secretion of pro-inflammatory cytokines,including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Additionally, compound 2 also markedlyreduced intracellular reactive oxygen species (ROS) generation in a dose-dependent manner, as confirmed byDCFDA fluorescence assay, and DPPH radical scavenging activity. These results indicate that deglucosyl-methylenebis-phloridzin (2) may be used as an effective anti-inflammatory and antioxidant agent for the prevention or treatmentof inflammatory diseases.