Magnolol ameliorates lipopolysaccharide-induced acute lung injury in rats through PPAR-γ-dependent inhibition of NF-kB activation

• Magnolol increases the PPAR-γ expression and activity in lungs instilled with LPS.
• Blocking PPAR-γ activity reverses the beneficial effects of magnolol in ALI.
• PPAR-γ involves magnolol-mediated suppression of NF-kB activation and inflammation.
• The protective effect of magnolol in LPS-induced ALI is mediated by PPAR-γ.

Acute lung injury (ALI) has a high morbidity and mortality rate due to the serious inflammation and edema occurred in lung. Magnolol extracted from Magnolia officinalis, has been reported to exhibit anti-inflammatory, and antioxidant activities. Peroxisome proliferator-activated receptors (PPARs) are known to exert a cytoprotective effect against cellular inflammatory stress and oxidative injury. The aim of this study was to explore the involvement of PPAR-γ in the beneficial effect of magnolol in lipopolysaccharide (LPS)-induced ALI. We found that treatment with magnolol greatly improved the pathological features of ALI evidenced by reduction of lung edema, polymorphonuclear neutrophil infiltration, ROS production, the levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), the expression of iNOS and COX-2, and NF-κB activation in lungs exposed to LPS. Importantly, magnolol is capable of increasing the PPAR-γ expression and activity in lungs of ALI. However, blocking PPAR-γ activity with GW9662 markedly abolished the protective and anti-inflammatory effects of magnolol. Taken together, the present study provides a novel mechanism accounting for the protective effect of magnolol in LPS-induced ALI is at least partly attributed to induction of PPAR-γ in lungs, and in turn suppressing NF-κB-related inflammatory responses.