Phloridzin reveals new treatment strategies for liver fibrosis

Liver fibrosis, is an urgent public health problem and is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of messenger RNA (mRNA) and long non-coding RNA (lncRNA) in different groups of liver tissues, and screened for differentially expressed genes, as well as performed gene co-expression analysis of the differential lncRNAs and mRNAs. The results showed that compared with the model group, the phloridzin treated groups showed a significant decrease in collagen deposition, and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell-substrate junctions, and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism and related changes in biomechanics. Overall design: The mice were randomly divided into 6 groups: the control group, model group, silibinin group, phloridzin low dose group, phloridzin middle dose group, and phloridzin high group.Liver fibrosis in the mouse model was induced by intraperitoneal injection of carbon tetrachloride (CCl4) dissolved in olive oil (1:9, v/v) at a dosage was 5 mL/kg body weight twice a week for 8 weeks. Drug therapy was started on the fifth week. After 8 weeks, the mice were sacrificed and the livers excised.