Forsythiae Fructuse extracts alleviates LPS-induced acute lung injury in mice by regulating PPAR-?/RXR-a in lungs and colons

Ethnopharmacological relevance: Forsythiae Fructuse (FF), the dried fruit of Forsythia suspensa (Thunb.) Vahl, is used as a traditional Chinese medicine that has been reported to exert good anti-inflammatory effects in the treatment of many lung diseases.& nbsp;Aim of the study: The purpose of this study was to investigate the anti-inflammatory mechanism of FF in the treatment of acute lung injury (ALI) based on gut-lung axis.& nbsp;Materials and methods: ALI model was established by the intratracheal instillation of 5 mg/kg LPS in ICR mice. Mice were administered intragastrically with dexamethasone (DEX), and low-dose, medium-dose and high-dose of FF extracts (LFF, MFF and HFF) in addition to the mice of control (CON) and model (MOD) groups. Pathological observation and inflammation scoring of lung tissues were based on HE staining. Limulus lysate assay was used to detect endotoxin levels in serum. Western blot and Real-time quantitative PCR were respectively applied to detect the protein and mRNA expressions in both lung and colon tissues.& nbsp;Results: Lung pathological injury, inflammatory score and inflammatory genes (IL-6, IL-1 beta, TNF-alpha) could be effectively suppressed by FF in LPS-induced ALI mice. FF also increased the proteins of epithelial markers (Ecadherin, ZO-1 and Claudin-1) in lung and colon tissues, and decreased colonic inflammatory genes for protecting the epithelial barriers of lung and colon. The protein expression of TLR4/MAPK/NF-kappa B inflammatory signaling pathway in lung and colon was significantly inhibited by FF via the regulation of PPAR-gamma, a nuclear hormone receptor that forms the heterodimer with RXR-alpha to inhibit inflammatory gene transcription. More specifically, FF promoted the upregulation of protein, phosphorylated proteins and genes of PPAR-gamma/RXR-alpha in lungs, while inhibited the protein overexpression and phosphorylation of PPAR-gamma/RXR-alpha in colons.& nbsp;Conclusions: FF exhibited anti-inflammatory effects and protected the epithelial barriers in lungs and colons by regulating PPAR-gamma/RXR-alpha in the treatment of LPS-induced ALI.