5,2'-Dibromo-2,4',5'-trihydroxydiphenylmethanone Inhibits LPS-Induced Vascular Inflammation by Targeting the Cav1 Protein

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 9; p. 2884
• Main Authors: Yuan, Hongxia, Hou, Qianyi, Feng, Xiue, Zhang, Yuanlin, Yang, Fan, Ge, Rui, Li, Qingshan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.04.2022; MDPI
• Subjects: 5,2′-dibromo-2,4′,5′-trihydroxydiphenylmethanone; Absorption spectra; Amino acids; Anti-Inflammatory Agents - therapeutic use; Arteriosclerosis; Atherosclerosis; Atherosclerosis - drug therapy; Binding sites; Caveolin; Caveolin 1 - metabolism; Caveolin-1; EA.hy926 cells; Fluorescence; Gene expression; Humans; Hydrogen bonding; Hydrogen bonds; In vivo methods and tests; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; lipopolysaccharide; Lipopolysaccharides; Lipopolysaccharides - adverse effects; Metabolism; Molecular docking; Molecular Docking Simulation; NF-kappa B - metabolism; NF-κB protein; NF-κB signaling; Phosphorylation; Polypeptides; Proteins; Signal transduction; Spectrum analysis; Temperature; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor necrosis factor-TNF; Van der Waals forces; vascular inflammation; Whooping cough; NF-κB signaling; caveolin-1; vascular inflammation; 5,2′-dibromo-2,4′,5′-trihydroxydiphenylmethanone; lipopolysaccharide; EA.hy926 cells
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27092884

Vascular inflammation is directly responsible for atherosclerosis. 5,2'-Dibromo-2,4',5'-trihydroxydiphenylmethanone (TDD), a synthetic bromophenol derivative, exhibits anti-atherosclerosis and anti-inflammatory effects. However, the underlying pathways are not yet clear. In this study, we first examined the effects of TDD on toll-like receptor-4 (TLR4) activity, the signaling receptor for lipopolysaccharide (LPS), and found that TDD does not inhibit LPS-induced TLR4 expression in EA.hy926 cells and the vascular wall in vivo. Next, we investigated the global protein alterations and the mechanisms underlying the action of TDD in LPS-treated EA.hy926 cells using an isobaric tag for the relative and absolute quantification technique. Western blot analysis revealed that TDD inhibited NF-κB activation by regulating the phosphorylation and subsequent degradation IκBα. Among the differentially expressed proteins, TDD concentration-dependently inhibited Caveolin 1(Cav1) expression. The interaction between Cav1 and TDD was determined by using biolayer interference assay, UV- absorption spectra, fluorescence spectrum, and molecular docking. We found that TDD can directly bind to Cav1 through hydrogen bonds and van der Waals forces. In conclusion, our results showed that TDD inhibited LPS-induced vascular inflammation and the NF-κB signaling pathway by specifically targeting the Cav1 protein. TDD may be a novel anti-inflammatory compound, especially for the treatment of atherosclerosis.