Antioxidant and Anti-Inflammatory Effects of 6,3’,4´- and 7,3´,4´-Trihydroxyflavone on 2D and 3D RAW264.7 Models

Abstract

Dietary flavones 6,3´,4´-trihydroxyflavone (6,3´,4´-HOFL) and 7,3´,4´-trihydroxyflavone (7,3´,4´-HOFL) showed preliminary antioxidant and anti-inflammatory activities in a two-dimensional (2D) cell culture model. However, their action mechanisms remain unclear, and the anti-inflammatory activities have not been studied in a reliable three-dimensional (3D) cell model. Therefore, in the current study, the antioxidant potency was examined by their scavenging ability of cellular reactive oxygen species. Anti-inflammatory activities were examined via their inhibitory effects on inflammatory mediators in vitro on 2D and 3D macrophage models, and their mechanisms were determined through transcriptome. In the 3D macrophages, two flavones were less bioactive than they were in 2D macrophages, but they both significantly suppressed the overexpression of proinflammatory mediators in two cell models. The divergent position of the hydroxyl group on the A ring resulted in activity differences. Compared to 6,3´,4´-HOFL, 7,3´,4´-HOFL showed lower activity on NO, IL-1β suppression, and c-Src binding (IC50: 12.0 and 20.9 µM) but higher ROS-scavenging capacity (IC50: 3.20 and 2.71 µM) and less cytotoxicity. In addition to the IL-17 and TNF pathways of 6,3´,4´-HOFL, 7,3´,4´-HOFL also exerted anti-inflammatory activity through JAK-STAT, as indicated by the RNA-sequencing results. Two flavones showed prominent antioxidant and anti-inflammatory activities on 2D and 3D models.

Iodine-PEG as a unique combination for the metal-free synthesis of flavonoids through iodonium-triiodide ion-pair complexation

“…It is reported to possess good anti-oxidant and anti-inflammatory activities in 2D and 3D cell culture models. 30 It is worth mentioning that hydroxy benzaldehydes were not reported in the previous studies 25,26 and in other reports, reactions were performed by protecting the hydroxy functionality. In addition, the hydroxy-substituted benzaldehydes were reported to display low reactivity due to phenoxide formation and results in the formation of several side products.…”

Polygonatum kingianum Polysaccharides Enhance the Preventive Efficacy of Heat-Inactivated Limosilactobacillus reuteri WX-94 against High-Fat-High-Sucrose-Induced Liver Injury and Gut Dysbacteriosis

“…Specifically, Lactobacilli in general can utilize a great variety of carbohydrates and phytochemicals, thereafter producing various bioactive ingredients with high bioavailability or pharmacological properties, − such as 3-phenyllactic acid, 2-hydroxy-3-(4-hydroxyphenyl)-propanoic acid, lactic acid, propionic acid, arachidic acid, trihydroxyflavone, kojic acid, and succinic acid. − Notably, the contents of these metabolites were significantly higher in the cell-free supernatant of L. reuteri incubated with PKP than in the MRS-cultured L.…”

Compound Classification and Consideration of Correlation with Chemical Descriptors from Articles on Antioxidant Capacity Using Natural Language Processing

“…9 These hold substantial medical value and are associated with specific chemical factors, such as the inhibition or promotion of enzymes. 9 The activity of antioxidants often results from complex interactions between various factors. 2 Therefore, comprehensively reading articles on antioxidants, not limited to those explicitly mentioning "antioxidants" but also those discussing their properties, is paramount for a thorough understanding.…”

“…Conversely, the singlet oxygen absorbance capacity (SOAC), , another metric of antioxidant capacity, is influenced by the energy difference between the ground and excited states . In addition to measurable antioxidant activity, certain substances exhibit clinically relevant antioxidant properties . These hold substantial medical value and are associated with specific chemical factors, such as the inhibition or promotion of enzymes .…”

“…In addition to measurable antioxidant activity, certain substances exhibit clinically relevant antioxidant properties . These hold substantial medical value and are associated with specific chemical factors, such as the inhibition or promotion of enzymes . The activity of antioxidants often results from complex interactions between various factors .…”