| Liver fibrosis plays an important and dangerous role in the progression of liver disease,and is a healing response triggered by chronic inflammation,which can be reversible in the initial stage,but long-term ineffective intervention will lead to liver cirrhosis and liver cancer,and there is still a lack of extensive and effective anti-fibrotic therapy.The concept of "livergut axis" provides a new idea for the study of the occurrence and reversibility of liver fibrosis,and the results show that the destruction of intestinal microecology affects the body’s metabolism and immune response,thereby accelerating the process of liver fibrosis,indicating that the regulation of intestinal microbiota may have an ameliorating effect on liver fibrosis.Cangzhu Erchen Oral Liquid is mainly used for the treatment of gastrointestinal diseases,and is composed of a variety of Chinese medicinal materials such as Atractylodes atractylodes,Indian Buead Tuckahoe,Tangerine Peel,etc.,which regulates the dampness in the body by strengthening the spleen and dissipating dampness,and plays a role in dissolving dampness and clearing heat.Pharmacological studies have shown that Cangzhu Erchen Oral Liquid can improve intestinal peristalsis,has antibacterial and anti-inflammatory effects,may have a regulatory effect on intestinal flora,and has a potential therapeutic effect on liver fibrosis The theoretical basis is consistent.Based on the positive effects of Cangzhu Erchen Oral Liquid on intestinal function,it may have a positive effect on balancing the microbiota,reducing inflammatory response,and ultimately improving liver fibrosis status.In this study,metagenomics was used to analyze the composition and functional evolution of intestinal microbiota in patients with liver fibrosis before and after treatment with Cangzhu Erchen Oral Liquid,and then to analyze the effect of the formula on intestinal microbiota and its possible therapeutic mechanism.Cangzhu Erchen Oral Liquid can alleviate the dose-dependent slowdown of abnormal hyperplasia of fibrous tissue in the liver,can effectively down-regulate the mRNA expression of the fibrosis marker proteins Collagen 1A1 and Fibronectin induced by CCl4,and can reduce the expression levels of α-SMA,Collagen 1A1 and Fibronectin.The results showed that Cangzhu Erchen Oral Liquid had a potential therapeutic effect on reversing CCl4-induced liver fibrosis,which reduced liver injury and fibrosis through a dose-dependent manner.This study provides an important basis for revealing the molecular mechanism of the effect of Cangzhu Erchen Oral Liquid on alleviating liver fibrosis.We systematically evaluated the anti-fibrotic effect of atractylodes atractylodes using animal models of liver fibrosis.In a carbon tetrachloride(CCl4)-induced mouse model of liver fibrosis,Atractylodes(Aty)was able to effectively improve the balance of intestinal microbiota,restore microbiota diversity,and cause positive changes in microbiota composition.At the phylum and genus levels,the bacterial taxa of Bacteroidota,Bacillota,Verrucomicrobiota,Actinomycetota,Muribaculum,Akkermansia and Duncaniella were the most abundant.The abundance of some species,such as Muribaculum and Akkermansia,decreased after CCl4 modeling and rebounded in the atractylodes ketone-treated group;Other microorganisms,such as Bifidobacterium animalis,were elevated in the model group and decreased in the Atractylodes atractylodes treatment group,suggesting that atractylodes may exert a therapeutic effect by adjusting the balance of intestinal microbiota.Alpha diversity index analysis revealed that atractylodes treatment could significantly improve the species diversity of intestinal microbiota.Beta diversity analysis revealed that there were significant differences in microbial communities between the groups.These changes suggest that atractylodes may exert a therapeutic effect by optimizing the ratio of intestinal flora.Differential metabolites associated with liver fibrosis during atractylodes ketone treatment were identified by high-throughput targeted metabolomics.These differential metabolites showed significant variation between samples or groups.For example,L-Glutamine(glutamine)and L-Lysine(lysine)were elevated before atractylodes treatment and decreased after administration;On the other hand,11Z-Eicosenoic Acid(arachidonic acid),Erucic Acid,L-Phenylalanine(phenylalanine)and Heneicosanoic acid(becosanic acid)decreased before treatment and increased after administration.The changes in these differential metabolites suggest that the treatment of liver fibrosis by atractylodes ketone may be achieved by modulating multiple metabolic pathways,and provide clues for further study of its mechanism of action.This study will combine science with traditional Chinese medicine theory to provide new experimental evidence for the application of Cangzhu Erchen Oral Liquid in the treatment of liver fibrosis and related diseases,and also open up new ideas for the comprehensive treatment strategy of liver fibrosis.By understanding the regulatory mechanism of intestinal microbiota and the association between them and liver diseases,it is expected to provide a new therapeutic target for the treatment of liver fibrosis,so as to improve the prognosis of patients and contribute to human health.Future research directions include continuing to study the mechanism of action of atractylodes ketone on liver fibrosis and studying its effects on other organ systems of the body.At the same time,we will also explore therapeutic strategies for atractylodes in combination with other treatment modalities such as chemotherapy and radiotherapy,and study the interaction of metabolites with the genome,proteome,transcriptome and epibiome.In addition,we will further explore how computer models and machine learning algorithms can be applied to elucidate the mechanism of action of differential metabolites in the treatment of liver fibrosis,so as to guide clinical practice more accurately and practically.Given the limitations of the study,such as differences between animal models and humans,and the lack of systematic studies of other TCM components,our findings still need to be interpreted with caution.Future studies should include metagenomic analysis of the gut microbiome of human patients with liver fibrosis to verify the efficacy and safety of atractylodesone;At the same time,exploring the specific effects of atractylodes on intestinal microbiota and the role of gut-liver axis in the treatment of liver fibrosis by atractylodes are also the focus of future work.In summary,the results of this study provide a new perspective to expand our understanding of the treatment of liver fibrosis,but this treatment still needs to undergo a lot of research and validation work before it can be applied to human treatment.The in-depth study of atractylodes may provide new avenues for future personalized medicine strategies,especially in the regulation of the gut microbiome and drug therapy.We look forward to the potentially transformative treatments that atractylodes are a traditional Chinese medicine ingredient and its potential to improve the health of patients with liver fibrosis and other related liver diseases on a global scale.In conclusion,this study made full use of high-throughput targeted metabolomics technology in the study of atractylodes atractylodes against liver fibrosis.The identification of differential metabolites can help develop new therapeutic strategies in translational medicine and support the conduct of relevant clinical studies.This is important for the early detection of effective treatments for liver fibrosis and for accelerating research into liver diseases. |
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