The natural course of
otitis media in children is acute and self-limiting. Nevertheless, about 10-20% children could experience recurrent or persistent
otitis media. Thus, finding effective candidate to prevent acute
otitis media is urgently required. In our study, mouse acute
otitis media model was constructed by
lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane.
Apigetrin (
APT) is a
flavonoid isolated from various
herbal medicines, possessing anti-inflammatory and anti-oxidative bioactivities. However, if
APT could attenuate acute
otitis media in LPS-induced animal models, little is to be known.
Hematoxylin and
eosin (H&E) staining suggested that
APT treatment reduced LPS-induced higher mucosa thickness. LPS-triggered inflammatory response was also inhibited by
APT, as evidenced by the down-regulated neutrophils and macrophages. Additionally, the reduced inflammatory factors, including interleukin-1β (IL-lβ),
tumor necrosis factor α (TNF-α),
IL-6 and
vascular endothelial growth factor (
VEGF) were observed in
APT-treated mice with acute
otitis media. The process was associated with the inhibition of
toll-like receptor 4 (TLR4)/
nuclear factor kappa B (NF-κB) pathway, which was proved by the blockage of TLR4, MyD88, p-IKKα, p-IκBα, and p-NF-κB using western blot analysis. Moreover, the production of
reactive oxygen species (ROS) caused by LPS was also reduced by
APT through promoting
anti-oxidants, involving
superoxide dismutase (SOD) activity,
heme oxygenase-1 (HO-1),
NADP(H)
quinone oxidoreductase 1 (NQO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions. In contrast, high levels of MDA and
kelch-like ECH-associated protein 1 (Keap 1) in LPS-treated mice were down-regulated by
APT, which might be associated with the inactivation of NF-κB. In vitro,
APT exhibited anti-inflammatory and
anti-oxidant effects with little cytotoxicity in LPS-stimulated cells. Together, the data above indicated that
APT could ameliorate acute
otitis media through inhibiting
inflammation and oxidative stress.