Dataset Information

The Modulation of Chaihu Shugan Formula on Microbiota Composition in the Simulator of the Human Intestinal Microbial Ecosystem Technology Platform and its Influence on Gut Barrier and Intestinal Immunity in Caco-2/THP1-Blue™ Cell Co-Culture Model.

ABSTRACT: The traditional Chinese medicine (TCM)-Chaihu Shugan Formula (CSF), consisting of several Chinese botanical drugs like Bupleurum, is derived from the ancient Chinese pharmacopeia. It has been used for more than thousands of years in various suboptimal health statuses and diseases induced by chronic stress based on empirical therapy. Recent studies confirm the role of CSF in the development of many diseases, including depression, stress-induced hepatic injury and tumors. However, little has been known about the mechanisms behind the health effects of CSF. Here, we investigate the influence of CSF on the modulation of the simulated colonic microbiota of five healthy donors, gut barrier integrity, and intestinal immunity by combining the simulator of the human intestinal microbial ecosystem (SHIME^®) technology platform with co-culture of intestinal and immune cells. This approach revealed that CSF stimulated the production of SCFA (acetate, propionate and butyrate) across donors while significantly lowering the production of branched SCFA (bSCFA). In terms of community composition, CSF stimulated a broad spectrum of health-related Bifidobacterium species, which are potent acetate and lactate producers. At the same time, it lowered the abundance of opportunistic pathogenic Escherichia coli. Later, we explore the effect of colonic fermentation of CSF on the gut barrier and intestinal immunity in the Caco-2/THP1-blue™ cell co-culture model. Based on the study using SHIME technology platform, CSF showed protective effects on inflammation-induced intestinal epithelial barrier disruption in all donors. Also, the treatment of CSF showed pronounced anti-inflammatory properties by strongly inducing anti-inflammatory cytokines IL-6 and IL-10 and reducing pro-inflammatory cytokine TNF-α. These findings demonstrate a significant modulatory effect of CSF on intestinal gut microbiota. CSF-microbial fermentation products improved the gut barrier and controlled intestinal inflammation.

SUBMITTER: Liu L

PROVIDER: S-EPMC8964513 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Breast cancer is one of the most common cancers endangering women's health all over the world. Traditional Chinese medicine is increasingly recognized as a possible complementary and alternative therapy for breast cancer. Chaihu-Shugan-San is a traditional Chinese medicine prescription, which is extensively used in clinical practice. Its therapeutic effect on breast cancer has attracted extensive attention, but its mechanism of action is still unclear. In this study, we explored the molecular mechanism of Chaihu-Shugan-San in the treatment of breast cancer by network pharmacology. The results showed that 157 active ingredients and 8074 potential drug targets were obtained in the TCMSP database according to the screening conditions. 2384 disease targets were collected in the TTD, OMIM, DrugBank, GeneCards disease database. We applied the Bisogenet plug-in in Cytoscape 3.7.1 to obtain 451 core targets. The biological process of gene ontology (GO) involves the mRNA catabolic process, RNA catabolic process, telomere organization, nucleobase-containing compound catabolic process, heterocycle catabolic process, and so on. In cellular component, cytosolic part, focal adhesion, cell-substrate adherens junction, and cell-substrate junction are highly correlated with breast cancer. In the molecular function category, most proteins were addressed to ubiquitin-like protein ligase binding, protein domain specific binding, and Nop56p-associated pre-rRNA complex. Besides, the results of the KEGG pathway analysis showed that the pathways mainly involved in apoptosis, cell cycle, transcriptional dysregulation, endocrine resistance, and viral infection. In conclusion, the treatment of breast cancer by Chaihu-Shugan-San is the result of multicomponent, multitarget, and multipathway interaction. This study provides a certain theoretical basis for the treatment of breast cancer by Chaihu-Shugan-San and has certain reference value for the development and application of new drugs.

Project description:ObjectiveChaihu Shugan San (CSS) is a common antidepressant prescription in traditional Chinese medicines. However, its active ingredients and mechanisms are unknown. The aim of this study was to explore the potential active ingredients and pharmacological mechanisms of CSS for the treatment of major depressive disorder (MDD).MethodsActive compounds in CSS were screened using the Traditional Chinese Medicine Systems Pharmacology database. Compound-related targets were retrieved using the SwissTargetPrediction database. MDD-related targets were determined using DisGeNET, Therapeutic Target Database and DrugBank databases. The common targets of active compounds in CSS and MDD were retained to construct a compound-MDD target network. Then, functional enrichment analysis and protein-protein interaction analysis were performed to identify hub targets and explore the underlying molecular mechanisms. Finally, hub-targeted genes and pathways were validated by Western blotting and immunofluorescence using chronic unpredictable mild stress (CUMS) mice with or without CSS treatment. The affinities between the active compounds in CSS and hub-targeted genes were evaluated by molecular docking.ResultsNetwork pharmacology analysis revealed 24 potential targets for treatment of MDD by CSS. Functional enrichment analysis showed that PI3K/AKT signaling pathway was likely to be evidently affected by CSS in the treatment of MDD. In vivo experiments showed that CSS could improve depressive-like behaviors and promote neurogenesis in CUMS mice. Furthermore, CSS could increase phosphorylated (p) PI3K/PI3K and pAKT/AKT levels and decrease the pGSK3β/GSK3β level in the hippocampus of CUMS mice. The active compounds mainly included quercetin and luteolin, which showed good docking scores targeting the PI3K protein.ConclusionThis network pharmacological and experimental study highlights that the PI3K/AKT pathway is the potential mechanism by which CSS is involved in MDD treatment. Quercetin, luteolin, and kaempferol are probable active compounds in CSS, and these results might provide valuable guidance for further studies of MDD treatment.

Project description:Purpose:We explored the mechanism of Shugan Jianpi Formula (SGJPF) and its effective components for the treatment of liver fibrosis (LF). Materials and Methods:We collected the active ingredients in SGJPF through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and screened the effective components by absorption, distribution, metabolism, and excretion. Herb-associated target proteins were predicted and screened based on the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and Search Tool for Interactions of Chemicals databases. LF-associated target proteins were predicted and screened based on the Online Mendelian Inheritance in Man® Database and Comparative Toxicogenomics Database. Common genes with LF and herbs were selected, and Cytoscape 3.5.1 software was used to construct an herb pathway and component-LF common target network. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to build a protein-protein interaction, and quantitative PCR was used to verify the related target genes. Finally, clusterProfiler was applied for the analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results:The pharmacological network contained 252 active compounds (e.g., Astragaloside A, saikosaponin, linoleic acid, and Poria acid A), 84 common target genes, and 94 significant signaling pathways. Among them, interleukin 6 (IL-6), tumor protein 53 p53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), AKT1, IL-1?, and the nucleotide-binding and oligomerization domain-like receptor and Janus kinase-signal transducer and activator of transcription signaling pathways were selected as the critical target gene and critical signal pathway, respectively. Conclusion:The mechanisms of SGJPF in protecting against LF include the regulation of multiple targets such as IL-6, TP53, PTGS2, and AKT1. These target proteins affect LF through various signal transduction pathways.

Project description:Antibiotics are frequently used to treat bacterial infections; however, they affect not only the target pathogen but also commensal gut bacteria. They may cause the dysbiosis of human intestinal microbiota and consequent metabolic alterations, as well as the spreading of antibiotic resistant bacteria and antibiotic resistance genes (ARGs). In vitro experiments by simulator of the human intestinal microbial ecosystem (SHIME) can clarify the direct effects of antibiotics on different regions of the human intestinal microbiota, allowing complex human microbiota to be stably maintained in the absence of host cells. However, there are very few articles added the antibiotics into this in vitro model to observe the effects of antibiotics on the human intestinal microbiota. To date, no studies have focused on the correlations between the bloomed pathogens caused by amoxicillin (AMX) exposure and increased functional pathway genes as well as ARGs. This study investigated the influence of 600 mg day-1 AMX on human intestinal microbiota using SHIME. The impact of AMX on the composition and function of the human intestinal microbiota was revealed by 16S rRNA gene sequencing and high-throughput quantitative PCR. The results suggested that: (i) AMX treatment has tremendous influence on the overall taxonomic composition of the gut microbiota by increasing the relative abundance of Klebsiella [linear discriminant analysis (LDA) score = 5.26] and Bacteroides uniformis (LDA score = 4.75), as well as taxonomic diversity (Simpson, P = 0.067, T-test; Shannon, P = 0.061, T-test), and decreasing the members of Parabacteroides (LDA score = 4.18), Bifidobacterium (LDA score = 4.06), and Phascolarctobacterium (LDA score = 3.95); (ii) AMX exposure significantly enhanced the functional pathway genes and beta-lactam resistance genes, and the bloomed pathogens were strongly correlated with the metabolic and immune system diseases gene numbers (R = 0.98, P < 0.001) or bl2_len and bl2be_shv2 abundance (R = 0.94, P < 0.001); (iii) the changes caused by AMX were "SHIME-compartment" different with more significant alteration in ascending colon, and the effects were permanent, which could not be restored after 2-week AMX discontinuance. Overall results demonstrated negative side-effects of AMX, which should be considered for AMX prescription.

Dataset Information

The Modulation of Chaihu Shugan Formula on Microbiota Composition in the Simulator of the Human Intestinal Microbial Ecosystem Technology Platform and its Influence on Gut Barrier and Intestinal Immunity in Caco-2/THP1-Blue™ Cell Co-Culture Model.

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