Mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are pleiotropic regulator of many genes involved in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to reveal the protective effect of Isotetrandrine (ITD), a small molecule inhibitor, on various aspects of LPS-induced inflammation in vitro and in vivo.
METHODS AND RESULTS:
In vitro, RAW 264.7 cells were pretreated with different dose of Isotetrandrine 1 h before treatment with 1 mg/L of LPS. In vivo, to induce ALI, male BALB/c mice were injected intranasally with LPS and treated with Isotetrandrine (20 and 40 mg/kg) 1 h before LPS. In vitro, the cytokine levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in supernatant were reduced by Isotetrandrine. Meanwhile, in vivo, pulmonary inflammatory cell infiltration, myeloperoxidase activity, total cells, neutrophils, macrophages, along with the levels of tumor necrosis factor-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid were dose-dependently attenuated by Isotetrandrine. Furthermore, our data showed that Isotetrandrine significantly inhibited the activation of MAPK and NF-κB, which are induced by LPS in ALI model.
CONCLUSIONS:
These results suggested that Isotetrandrine dose-dependently suppressed the severity of LPS-induced ALI by inactivation of MAPK and NF-κB, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process. |
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