Andrographolide protects mice from influenza A induced-pneumonia via
regulation of the PI3K/AKT signaling pathway
Abstract
Influenza A virus (IAV) infection causes a frenzied host response, which
promotes acute lung inflammation. Andrographolide, an active component
extracted from Andrographis paniculate, exerts significant
inhibitive effects on acute inflammation induced by IAV. However, the
molecular mechanism of the anti-inflammatory and antiviral effects
remains poorly understood. Here, we found that andrographolide reduced
mortality, alleviated body weight loss, and decreased lung index and
inflammatory cytokines secretion rather than inhibiting viral
replication. Further study with RNA-seq analysis revealed that the
PI3K/AKT signaling pathway is significantly activated in the lungs of
andrographolide-treated mice. The phosphorylated AKT and PI3K were
significantly increased after andrographolide intervention by Western
blot. Moreover, [pyroptosis](javascript:;)-related proteins, and
downstream pathways of the PI3K/AKT signaling pathway, including
cleaved-caspase 3 and GSDME-N, were decreased. The protective effect of
andrographolide was significantly reduced after treatment with an AKT
inhibitor. In summary, our findings suggested that andrographolide
exerts a protective effect on IAV-induced [pneumonia](javascript:;)
by activating the PI3K/AKT signaling pathway, which may represent a
novel therapeutic strategy for IAV infection.