Qidong Huoxue decoction protects against acute lung injury by promoting SIRT1-mediated p300 deacetylation.

BACKGROUND

Qidong Huoxue Decoction (QD), a traditional Chinese medicine, has been used clinically to treat acute lung injury (ALI); however, its anti-inflammatory mechanisms remain poorly understood.

PURPOSE

This study aimed to elucidate the mechanism by which QD mitigates ALI, focusing on its anti-inflammatory effects.

METHODS

A combination of serum pharmacochemistry, acetyl-proteomic sequencing, and experimental validation was used to investigate the therapeutic effects of QD on ALI. Liquid chromatography-mass spectrometry (LC-MS) was used to profile the constituents of QD extract and their bioavailability in ALI mouse serum. Mice were randomly assigned to control or lipopolysaccharide (LPS) groups and treated with QD low-, medium-, or high-dose, or dexamethasone (DEX). Acetyl-proteomics was performed on lung tissues to identify key signaling pathways in LPS-induced ALI. RAW264.7 macrophages were used for in vitro confirmation of inflammation.

RESULTS

QD treatment markedly improved pulmonary function in ALI mice by reducing cytokine levels and inhibiting M1 macrophage polarization. Proteomic analysis revealed a significant downregulation of p300 acetylation in the QD-treated group, which was confirmed in vitro. Venn analysis of LC-MS data identified 298 constituents shared between the QD extract and drug-containing serum. Among these, resveratrol, a SIRT1 activator, was a major bioactive compound, suggesting its potential role in mediating the anti-inflammatory effects of QD.

CONCLUSION

QD alleviates ALI by suppressing p300 acetylation, probably by SIRT1 activation. These findings highlight the therapeutic potential of QD for epigenetic regulation of inflammatory signaling in ALI.