Sinensetin From Citrus Peel Alleviates LPS‐Induced Acute Pneumonia by Regulating HIF‐1α Signaling Pathway in Mice

Sinensetin, a key bioactive constituent of citrus peel, exhibits potent anti‐inflammatory properties. However, the mechanism by which SIN alleviates acute pneumonia remains unclear. This study established lipopolysaccharide (LPS)‐induced acute pneumonia models in vivo and in vitro. Sinensetin administration for 3 days significantly attenuated LPS‐induced acute pneumonia in mice, reducing lung injury, oxidative stress, and inflammation. Transcriptomic analysis implicated that sinensetin might improve acute pneumonia by modulating the HIF‐1 signaling pathway. Western blotting revealed that sinensetin suppressed HIF‐1α expression and phosphorylation of MAPK (p38, ERK1/2, JNK) in lung tissue. In LPS‐stimulated BEAS‐2B cells, sinensetin mitigated morphological damage and ROS accumulation while inhibiting NF‐κB and AP‐1 transcriptional activity. At the protein level, sinensetin reduced inflammatory factor expression, correlating with diminished HIF‐1α levels and MAPK phosphorylation. Crucially, HIF‐1α overexpression reversed the inhibitory effects of sinensetin on inflammatory factors and MAPK signaling. Collectively, these findings demonstrate that sinensetin alleviates acute pneumonia by regulating the HIF‐1α pathway.