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

Exposure to air pollution has been closely associated with some cardiovascular disease. One of the mechanisms of PM_2.5 -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 PM_2.5 , and to reveal the underlying mechanisms. The results showed that PM_2.5 increased the expression of certain inflammatory cytokines, and caused oxidative damage in BALB/c mice and H9C2 cells. Supplementation with 2-undecanone attenuated this PM_2.5 -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 PM_2.5 , 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 PM_2.5 , 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 PM_2.5 exposure.