Metabolic regulation and oxidative stress attenuation in LPS-stimulated macrophages by flavonoids.

Periodontal disease, prevalent in 20% to 50% of the population, is a chronic multifactorial inflammation caused by a dysbiotic oral biofilm, with gingivitis and periodontitis being the most common forms. Flavonoids, such as myricetin and catechin, have antioxidant and anti-inflammatory potential, reducing nitric oxide (NO) and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated macrophages. This study compared the effects of different flavonoids on viability and oxidative response of LPS-stimulated macrophages. RAW 264.7 macrophages were cultured at a density of 1-5 × 10⁵ cells for 24 h. Cells were treated with flavonoids epigallocatechin gallate (EGCG), taxifolin, myricetin, pinocembrin, and kaempferol (200 to 6.25 µM) for 2 h, and evaluated for cytotoxicity, using resazurin assays. Additionally, cells were treated with flavonoids (50, 25, and 12.5 µM) for 2 h, followed by exposure to LPS (100 ng/mL or 1 µg/mL) for 72 h, and cytotoxicity determined. NO and ROS levels were quantified after 2 h of flavonoid treatment, followed by LPS exposure (1 µg/mL), compared to control dexamethasone (DEX). LPS at 1 μg/mL significantly reduced cell viability (75.26%) and in its presence, taxifolin, myricetin, and kaempferol stimulated cell metabolic activity. All flavonoids, regardless of concentration, reduced NO levels when cells were treated with LPS. The flavonoids also reduced ROS levels, with EGCG and myricetin at 50 and 12.5 μM and kaempferol at 50 μM reducing levels to below those of the untreated control, as observed for DEX. The flavonoids, particularly EGCG, taxifolin, myricetin, and kaempferol, at the concentrations tested, stimulated macrophage metabolism, and reduced NO and ROS concentrations in the presence of LPS.