2-undecanone protects against fine particles-induced heart inflammation via modulating Nrf2/HO-1 and NF-κB pathways

Environ Toxicol. 2022 Jul;37(7):1642-1652. doi: 10.1002/tox.23513. Epub 2022 Mar 14.

Abstract

Exposure to air pollution has been closely associated with some cardiovascular disease. One of the mechanisms of PM2.5 -mediated heart injury may be to promote inflammation. We aim to investigate whether the main extract of Houttuynia cordata, 2-undecanone, can prevent the inflammation caused by PM2.5 , and to reveal the underlying mechanisms. The results showed that PM2.5 increased the expression of certain inflammatory cytokines, and caused oxidative damage in BALB/c mice and H9C2 cells. Supplementation with 2-undecanone attenuated this PM2.5 -induced inflammatory injury and oxidative damage. Further, we elucidated that the protective effect of 2-undecanone may be associated with NF-κB and Nrf2/HO-1 pathways. The NF-κB pathway was distinctly activated after treated by PM2.5 , which can be blocked by 2-undecanone, accompanied by increasing Nrf2 and HO-1 levels. To figure out the relationship between NF-κB and Nrf2/HO-1 pathways, we knocked down Nrf2 gene. NF-κB pathway proteins and downstream inflammatory cytokines were significantly increased after treatment with PM2.5 , while 2-undecanone could decrease expression of these proteins. In conclusion, it is possible that 2-undecanone can induce the expression of the antioxidant enzyme HO-1 by activating Nrf2, thereby reducing NF-κB pathway and inflammatory damage of mouse myocardium caused by PM2.5 exposure.

Keywords: 2-undecanone; HO-1; NF-κB; Nrf2; PM2.5.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Heme Oxygenase-1* / genetics
  • Heme Oxygenase-1* / metabolism
  • Inflammation / chemically induced
  • Inflammation / prevention & control
  • Ketones* / pharmacology
  • Mice
  • Myocarditis* / chemically induced
  • Myocarditis* / prevention & control
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • NF-kappa B* / genetics
  • NF-kappa B* / metabolism
  • Oxidative Stress
  • Particulate Matter / toxicity

Substances

  • Cytokines
  • Ketones
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Particulate Matter
  • Heme Oxygenase-1
  • undecan-2-one