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Phloridzin Reveals New Treatment Strategies for Liver Fibrosis
Yahong Shi1,2, Tun Yan1,2,3, Xi Lu1,2
1School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
Abstract:
Liver fibrosis is an urgent public health problem which 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 mRNA and lncRNA in different groups of liver tissues. The results showed that compared with the model group, the phloridzin-treated groups revealed 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.
Insights
Phloridzin, derived from lychee core, effectively treats liver fibrosis in mice by reducing collagen and key biochemical markers. Its mechanism involves regulating cell ferroptosis and carbon metabolism, offering a promising therapeutic avenue.
Area of Science:
- Hepatology
- Pharmacology
- Biochemistry
Background:
- Liver fibrosis is a significant health concern with limited effective treatments.
- Current therapies for liver fibrosis present challenges in clinical application.
- Phloridzin, a natural compound from lychee core, is explored for its therapeutic potential.
Purpose of the Study:
- To evaluate the efficacy of phloridzin in treating carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model.
- To elucidate the underlying molecular mechanisms of phloridzin's action in liver fibrosis.
- To investigate the impact of phloridzin on cellular processes like ferroptosis and metabolic pathways.
Main Methods:
- Induction of liver fibrosis using CCl4 in C57/BL6N mice.
- Administration of phloridzin to treated groups.
- Assessment of therapeutic effects via biochemical marker analysis and ultrasound detection.
- High-throughput mRNA and lncRNA sequencing for mechanistic insights.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.
Main Results:
- Phloridzin treatment significantly reduced collagen deposition in liver tissues.
- Key biochemical markers, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), laminin, and hyaluronic acid, were decreased.
- Pathway analysis indicated that phloridzin primarily influences cell ferroptosis.
- lncRNA analysis revealed associations with focal adhesions, intercellular adhesion, cell-substrate junctions, and carbon metabolism.
Conclusions:
- Phloridzin demonstrates significant therapeutic efficacy against liver fibrosis.
- The mechanism of action involves modulation of cell ferroptosis and carbon metabolism.
- Phloridzin may also impact biomechanical properties related to cell adhesion and extracellular matrix.
- Phloridzin represents a potential novel therapeutic agent for liver fibrosis.
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