Ellagic Acid Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting Wnt Signaling Pathway
Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality, which characterized by epithelial cell damage and fibroblasts activation. Ellagic acid (EA) is a natural polyphenol compound widely found in fruits and nuts which has demonstrated multiple pharmacological activities. Herein we showed that Ellagic acid significantly alleviated bleomycin(BLM)-induced pulmonary fibrosis in mice, and also inhibited the Wnt/β-catenin signal in primary pulmonary fibroblasts. In vitro experiments indicated that Ellagic acid apparently suppressed Wnt3a-induced myofibroblasts activation and ECM accumulation mainly via inhibiting the phosphorylation of Erk2 and Akt. Further studies showed that Ellagic acid could induce autophagy formation of myofibroblasts mainly by suppressing mTOR signaling and promote apoptosis of myofibroblasts. In vivo experiments reveled that Ellagic acid significantly inhibited myofibroblasts activation and promoted autophagy formation. Taken together, our results showed that Ellagic acid effectively attenuated BLM-induced pulmonary fibrosis in mice by suppressing myofibroblasts activation, promoting autophagy and apoptosis of myofibroblasts mainly via inhibiting Wnt signaling pathway.