7,8-dihydroxyflavone displayed antioxidant effect through activating HO-1 expression and inhibiting caspase-3/PARP activation in RAW264.7 cells

J Biochem Mol Toxicol. 2024 Jan;38(1):e23602. doi: 10.1002/jbt.23602. Epub 2023 Dec 5.

Abstract

Flavonoids, which contain a benzo-γ-pyrone (C6-C3-C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8-dihydroxyflavone (7,8-DHF) and 7-hydroxyflavone (7-HF) in H2 O2 , lipopolysaccharide (LPS), or tert-butyl hydroperoxide (t-BHP)-induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8-DHF and 7-HF were firstly evaluated by 2,2-azinobis-3-ethyl-benzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7-HF and 7,8-DHF were initially investigated by western blot. Our results showed that 7,8-DHF possessed stronger free-radical scavenging capacity than 7-HF. Both 7,8-DHF and 7-HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells, respectively. And 7,8-DHF exerted a better antioxidant effect than 7-HF, especially in t-BHP-induced oxidative stress. Mechanically, 7,8-DHF prevented the activation of poly ADP-ribosepolymerase and caspase-3, meanwhile markedly upregulated the expression of HO-1 protein in t-BHP-induced oxidative stress. These results suggested that 7,8-DHF might serve as a potential pharmaceutical drug against oxidative stress injury.

Keywords: 7,8-dihydroxyflavone; 7-hydroxyflavone; RAW264.7 cells; cellular apoptosis; oxidative stress.

MeSH terms

  • Animals
  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Caspase 3 / metabolism
  • Flavones*
  • Lipopolysaccharides / toxicity
  • Mice
  • Oxidative Stress
  • Poly(ADP-ribose) Polymerase Inhibitors* / pharmacology
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • 6,7-dihydroxyflavone
  • Antioxidants
  • Caspase 3
  • Flavones
  • Lipopolysaccharides
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Reactive Oxygen Species
  • Superoxide Dismutase
  • LIN-49 protein, C elegans