Myricetin Alleviates Formaldehyde‐Exacerbated Inflammation in Asthmatic Mice Through Inhibition of Ferrous Iron Accumulation in Pulmonary Macrophages

Myricetin, a natural flavonoid known for its anti-inflammatory bioactivity, has also been documented as a chelator of iron in cells. The aim of the study was to examine whether myricetin could alleviate formaldehyde (FA)-exacerbated asthmatic inflammation through chelation of Fe(II). In this study, FA exposure at 2.0 mg/m3 exacerbated inflammation in lung tissues and induced iron accumulation and pro-inflammatory responses in pulmonary macrophages (PMs) in ovalbumin-induced asthmatic murine models, which was abated by deferoxamine via Fe(II) removal. Myricetin administration at 100 mg/kg relieved FA-exacerbated inflammation and alleviated Fe(II) overload in PMs. Myricetin treatment in isolated PMs cultured in vitro at 50 µM also attenuated pro-inflammatory responses of PMs through restoration of iron homeostasis. The results in this study not only showed that FA could enhance inflammatory condition in asthma through increased Fe(II) accumulation in PMs but also demonstrated the anti-inflammatory activity of myricetin via Fe(II) chelation in both FA-exacerbated asthmatic mice and in vitro PMs. Therefore, myricetin has the potential to be developed as a therapeutic agent for inflammatory conditions related to FA exposures.