High-mobility group box 1 (
HMGB1) is a highly conserved
DNA-binding
nuclear protein that facilitates gene transcription and the DNA repair response. However,
HMGB1 may be released by necrotic cells as well as activated monocytes and macrophages following stimulation with
lipopolysaccharide (LPS), interleukin-1β (IL-1β), or
tumor necrosis factor-α (TNF-α). Extracellular
HMGB1 plays a critical role in the pathogenesis of
acute lung injury (ALI) through activating the nuclear
transcription factor κB (NF-κB) P65 pathway, thus, it may be a promising therapeutic target in
shock-induced ALI.
Paeonol (Pae) is the main active component of Paeonia suffruticosa, which has been used to inhibit the inflammatory response in
traditional Chinese medicine. We have proven that Pae inhibits the expression, relocation and secretion of
HMGB1 in vitro. However, the role of Pae in the HMGB1-NF-κB pathway remains unknown. We herein investigated the role of Pae in LPS-induced ALI rats. In this study, LPS induced a marked decrease in the mean arterial pressure (MAP) and survival rate (only 25% after 72 h), and induced severe pathological changes in the lung tissue of rats, which was accompanied by elevated expression of
HMGB1 and its downstream
protein NF-κB P65. Treatment with Pae significantly improved the survival rate (>60%) and MAP, and attenuated the pathological damage to the lung tissue in ALI rats. Western blotting revealed that Pae also inhibited the total expression of
HMGB1, NF-κB P65 and TNF-α in the lung tissue of ALI rats. Moreover, Pae increased the expression of
HMGB1 in the nucleus, inhibited the production of
HMGB1 in the cytoplasm, and decreased the expression of P65 both in the nucleus and cytoplasm of lung tissue cells in LPS-induced ALI rats. The results were in agreement with those observed in the in vitro experiment. These findings indicate that Pae may be a potential treatment for ALI through its repression of the HMGB1-NF-κB P65 signaling pathway.