Pinocembrin relieves lipopolysaccharide and bleomycin induced lung inflammation via inhibiting TLR4-NF-κB-NLRP3 inflammasome signaling pathway.

Inflammation is a defense response of the body to stimuli. Lung injury caused by external stimuli can stimulate inflammatory cells to accumulate at the site of injury and secrete cytokines. Pinocembrin is a flavonoid with anti-inflammatory effects. Based on previous studies, we further explored the anti-inflammatory mechanisms of pinocembrin in vitro and in vivo. In vitro studies indicated that pinocembrin inhibited lipopolysaccharide (LPS)-stimulated inflammatory response in macrophages. In vivo studies also showed that pinocembrin could reduce LPS and bleomycin (BLM) induced lung inflammatory response in mice. Further mechanistic studies indicated that pinocembrin could regulate the TLR4-NF-κB signaling pathway and suppressed the activation and assembly of NLRP3 inflammasomes. In summary, pinocembrin could relieve pulmonary inflammatory response induced by LPS and BLM mainly via inhibiting TLR4-NF-κB-NLRP3 inflammasome axis. These results contribute to the understanding of the anti-inflammatory mechanisms of pinocembrin and serve as reference for future research on pinocembrin.

Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-ß1 signalling pathway.

OBJECTIVES: Anlotinib hydrochloride (AL3818) is a novel multitarget tyrosine kinase inhibitor which has the same targets as nintedanib, an effective drug has been approved for the treatment of idiopathic pulmonary fibrosis. Here, we examined whether anlotinib could also attenuate bleomycin-induced pulmonary fibrosis in mice and explored the antifibrosis mechanism. METHODS: We have evaluated the effect of anlotinib on bleomycin-induced pulmonary fibrosis in mice. Inflammatory cytokines in alveolar lavage fluid including IL-1ß, IL-4, IL-6 and TNF-α were determined by ELISA. Biomarkers of oxidative stress were measured by corresponding kit. Histopathologic examination was analysed by H&E staining and immunohistochemistry. In vitro, we investigated whether anlotinib inhibited TGFß/Smad3 and non-Smad pathways by luciferase assay or Western blotting. We also evaluated whether anlotinib inhibited TGF-ß1-induced epithelial-mesenchymal transition (EMT) and promoted myofibroblast apoptosis in order to explore the possible molecular mechanism. KEY FINDINGS: The results indicated that anlotinib treatment remarkably attenuated inflammation, oxidative stress and pulmonary fibrosis in mouse lungs. Anlotinib could inhibit the TGF-ß1 signalling pathway. Additionally, anlotinib not only profoundly inhibited TGF-ß1-induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and promoted the apoptosis in fibroblasts. CONCLUSIONS: In summary, the results suggest that anlotinib-mediated suppression of pulmonary fibrosis is related to the inhibition of TGF-ß1 signalling pathway.