Polyphenol-rich blue honeysuckle extract alleviates silica-induced lung fibrosis by modulating Th immune response and NRF2/HO-1 MAPK signaling

Blue honeysuckles are rich in polyphenol compounds that exert many beneficial effects. Previously, we demonstrated that polyphenol-rich blue honeysuckle extract (BHE) could alleviate silica-induced lung inflammation; however, its role in anti-fibrosis effects remains unknown. Here, we applied polyphenol-rich BHE to silica-injured mice to investigate its anti-fibrosis effect and the underlying mechanism. The results showed that BHE alleviated silica-induced pulmonary fibrosis in mice by altering regulatory T cell activity and mitigating T helper (Th)1/Th17 responses, resulting in reduced Th2 cytokine and transcription-factor mRNA levels. Additionally, cell-signaling detection revealed that p38 and c-Jun N-terminal kinase phosphorylation were effectively blocked by BHE treatment, which also downregulated the expression of inducible nitric oxide synthase and upregulated two antioxidant mediators [nuclear factor (erythroid-derived 2)-like 2 and heme oxygenase-1] in the lung. These findings support the use of BHE as functional food to modulate immune responses and alleviate lung fibrosis.