Pectolinarigenin Attenuates LPS-Induced Lung Inflammation and Injury with Reduced HDAC3/NF-κB/NLRP3 Signaling

Area of Science:

• Biochemistry
• Immunology
• Pharmacology

Background:

• Pectolinarigenin (PEC) is a flavonoid with known anti-inflammatory and antioxidant properties.
• The specific protective mechanisms of PEC against lipopolysaccharide (LPS)-induced lung inflammation are not well understood.

Purpose of the Study:

• To investigate the protective effects of PEC against LPS-induced lung inflammation.
• To elucidate the molecular mechanisms underlying PEC's action, focusing on oxidative stress and specific signaling pathways.

Main Methods:

• In vitro studies using LPS-treated MLE12 cells and RAW264.7 macrophages.
• In vivo studies using a prophylactic mouse model pretreated with PEC before LPS exposure.
• Analysis of inflammatory responses, cellular injury, reactive oxygen species, and the histone deacetylase 3 (HDAC3)/nuclear factor κB (NF-κB)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) signaling pathway.

Main Results:

• PEC reduced inflammatory responses, cellular injury, and reactive oxygen species in both cell models.
• In mice, PEC pretreatment attenuated pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokine production, oxidative stress, pyroptosis, and lung histopathology.
• These effects were associated with decreased HDAC3 expression and nuclear localization, and suppressed NF-κB/NLRP3 signaling.

Conclusions:

• Pectolinarigenin effectively attenuates LPS-induced lung inflammation and injury.
• PEC exerts its protective effects by reducing oxidative stress and modulating the HDAC3/NF-κB/NLRP3 signaling pathway.
• These findings suggest PEC has potential as a preventive agent for pulmonary inflammation.