Licochalcone A Inhibits Lipopolysaccharide-Induced Inflammatory Response in Vitro and in Vivo

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), is known for its antimicrobial activity and its reported ability to inhibit cancer cell proliferation. In the present study, we found that Lico A exerted potent anti-inflammatory effects in in vitro and in vivo models induced by lipopolysaccharide (LPS). The concentrations of TNF-alpha, interleukin (IL)-6, and IL-1 beta in the culture supernatants of RAW 264.7 cells were determined at different time points following LPS administration. LPS (0.5 mg/kg) was instilled intranasally (in.) in phosphate-buffered saline to induce acute lung injury, and 24 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator and total cell counts. The phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappa B) p65 protein was analyzed by Western blotting. Our results showed that Lico A significantly reduced the amount of inflammatory cells, the lung wet-to-dry weight (W/D) ratio, protein leakage, and myeloperoxidase activity and enhances oxidase dimutase activity in mice with LPS-induced acute lung injury (ALT). Enzyme-linked immunosorbent assay results indicated that Lico A can significantly down-regulate TNF-alpha, IL-6, and IL-1 beta levels in vitro and in vivo, and treatment with Lico A significantly attenuated alveolar wall thickening, alveolar hemorrhage, interstitial edema, and inflammatory cells infiltration in mice with ALI. In addition, we further demonstrated that Lico A exerts an anti-inflammation effect in an in vivo model of acute lung injury through suppression of NF-kappa B activation and p38/ERK MAPK signaling in a dose-dependent manner.