Shi Yahong, Yan Tun, Lu Xi, Li Kai, Nie Yifeng, Jiao Chuqiao, Sun Huizhen, Li Tingting, Li Xiang, Han Dong
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
National Center for Nanoscience and Technology, Beijing 100190, China.
Pharmaceuticals (Basel). 2022 Jul 20;15(7):896. doi: 10.3390/ph15070896.
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 CCl-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.
肝纤维化是一个亟待解决的公共卫生问题。然而,临床实践中用于治疗肝纤维化的各种药物在使用过程中都有各自的问题。在本研究中,我们使用从中药荔枝核中提取的根皮苷来治疗CCl诱导的C57/BL6N小鼠模型中的肝纤维化。通过生化指标检测和超声检测评估治疗效果。此外,为了确定根皮苷治疗肝纤维化的机制,我们对不同组肝组织中的mRNA和lncRNA进行了高通量测序。结果表明,与模型组相比,根皮苷治疗组的胶原沉积显著减少,血清丙氨酸转氨酶、天冬氨酸转氨酶、层粘连蛋白和透明质酸水平降低。对差异mRNA进行了GO和KEGG通路富集分析,结果显示根皮苷主要影响细胞铁死亡。基因共表达分析表明,lncRNA的靶基因在粘着斑、细胞间粘附和细胞-基质连接等细胞成分以及碳代谢等代谢途径中较为明显。这些结果表明,根皮苷可以有效治疗肝纤维化,其机制可能涉及铁死亡、碳代谢以及生物力学的相关变化。