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

Wang, Xiang1; Cao, Yujia1; Chen, Siyu1; Yang, Xin1; Bian, Jinsong2,3; Huang, Dejian1,2

2023

10.3390/antiox12010204

ANTIOXIDANTS   Impact Factor & Quartile

2076-3921

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-1 beta suppression, and c-Src binding (IC50: 12.0 and 20.9 mu M) but higher ROS-scavenging capacity (IC50: 3.20 and 2.71 mu M) 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.

6,3',4'-trihydroxyflavone 7,3',4'-trihydroxyflavone cellular-Src tyrosine kinase antioxi-dant anti-inflammation 3D macrophage model

SCI

English

Others

Singapore Ministry of Education[R-160-000-04-114]

Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Food Science & Technology

Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Food Science & Technology

WOS:000917244000001

MDPI

Web of Science

1.Natl Univ Singapore, Dept Food Sci & Technol, 2 Sci Dr 2, Singapore 117542, Singapore
2.Natl Univ Singapore, Suzhou Res Inst, 377 Linquan St, Suzhou 215123, Peoples R China
3.Southern Univ Sci & Technol, Sch Med, Dept Pharmacol, Shenzhen 518055, Peoples R China

Wang, Xiang,Cao, Yujia,Chen, Siyu,et al. Antioxidant and Anti-Inflammatory Effects of 6,3',4' - and 7,3',4' -Trihydroxyflavone on 2D and 3D RAW264.7 Models[J]. ANTIOXIDANTS,2023,12(1).

Wang, Xiang,Cao, Yujia,Chen, Siyu,Yang, Xin,Bian, Jinsong,&Huang, Dejian.(2023).Antioxidant and Anti-Inflammatory Effects of 6,3',4' - and 7,3',4' -Trihydroxyflavone on 2D and 3D RAW264.7 Models.ANTIOXIDANTS,12(1).

Wang, Xiang,et al."Antioxidant and Anti-Inflammatory Effects of 6,3',4' - and 7,3',4' -Trihydroxyflavone on 2D and 3D RAW264.7 Models".ANTIOXIDANTS 12.1(2023).