Suppressive effect of resveratrol, catechin and their conformationally constrained analogs on neutrophil extracellular trap formation by HL-60-derived neutrophils

• Published in: Journal of Clinical Biochemistry and Nutrition Vol. 75; no. 1; pp. 17 - 23
• Main Authors: Ohinata, Hitomi, Phimarn, Wiraphol, Mizuno, Mirei, Obama, Takashi, Fukuhara, Kiyoshi, Makiyama, Tomohiko, Watanabe, Yuichi, Itabe, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Japan SOCIETY FOR FREE RADICAL RESEARCH JAPAN 01.01.2024; Japan Science and Technology Agency
• Subjects: Acetic acid; Analogs; Aromatic compounds; Arteriosclerosis; Atherosclerosis; Calcium compounds; Calcium ionophores; Catechin; Conformation; Constraints; Deoxyribonucleic acid; DNA; HL-60; Hydrophobicity; Lecithin; Leukocytes (neutrophilic); neutrophil extracellular trap; Neutrophils; Peroxidase; Phosphatidylcholine; Phospholipids; planar analog; Resveratrol; catechin; HL-60; resveratrol; planar analog; neutrophil extracellular trap
• ISSN: 0912-0009; 1880-5086
• DOI: 10.3164/jcbn.23-80

Neutrophil extracellular trap (NET) formation is a unique self-defense mechanism of neutrophils; however, it is also involved in many diseases, including atherosclerosis. Resveratrol and catechin are antioxidants with anti-atherosclerotic properties. Here, we examined the effects of resveratrol, catechin, and other related compounds on NET formation. HL-60-derived neutrophils were pretreated with resveratrol and other compounds before stimu­lation with phorbol-myristate acetate (PMA). DNA and myelo­peroxidase released from neutrophils were determined. Res­ver­a­trol suppressed the DNA release from neutrophils in a dose-dependent manner. NET formation was enhanced by 1-palmitoyl-2-oxovaleroyl phosphatidylcholine (POVPC), a truncated form of oxidized phospholipid, and resveratrol suppressed NET formation induced by POVPC and PMA. Furthermore, we designed several analogs of resveratrol or catechin whose conformation was restricted by the inhibition of the free rotation of aromatic rings. The conformationally constrained analogs were more effective at ‍inhibiting NET formation; however, their inhibitory function decreased when compound was a large, hydrophobic analog. The ‍most potent compounds, planar catechin and resveratrol, suppressed myeloperoxidase release from activated neutrophils. In addition, these compounds suppressed DNA release from neutrophils stimulated with calcium ionophore. These results suggest that resveratrol, catechin and their analogs exert anti-NET effects, and that constraining the geometry of these compounds enhanced their inhibitory effects.