A Network Pharmacology-Based Study of the Mechanism of Renshen Baidu Powder in Treating Ulcerative Colitis

Abstract Ulcerative colitis (UC), one forms of chronic inflammatory bowel disease (IBD), is characterized by recurrent inflammation, and Renshen Baidu Powder (RSBDP) is often used as a traditional Chinese medicine prescription for treating of UC, but the pharmacological mechanisms remains unclear. This research aims to explore the mechanisms of RSBDP in the treatment of UC based on network pharmacology. Through multiple databases collected the compounds and targets, and constructed the network. The crossover genes enrichment analysis were performed by protein-protein interaction (PPI) construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, 181 compounds and 266 targets were obtained. Potential candidate ingredients mainly include phytosterols, flavonoids, and coumarins, all of which have anti-inflammatory activities. GO and KEGG enrichment analysis suggested that RSBDP have anti-inflammatory and immunomodulatory effects. The effect of RSBDP on UC might be achieved by regulating the balance of cytokines (i.e., IL-6, TNF, IL-1) and the downstream mediators (i.e., STAT1, STAT3) in the immune system. And inflammation-, immune- and hypoxic-related pathways, like TNF, Toll-like receptors and HIF-1 signaling pathway. These results provide a theoretical basis for studying the effective substances of RSBDP in the treatment of UC and their mechanism of action for further research.

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Uncovering the mechanism of Ge-Gen-Qin-Lian decoction for treating ulcerative colitis based on network pharmacology and molecular docking verification

Bioscience Reports ◽

10.1042/bsr20203565 ◽

2021 ◽

Vol 41 (2) ◽

Author(s):

Lin Xu ◽

Jiaqi Zhang ◽

Yifan Wang ◽

Zedan Zhang ◽

Fengyun Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Molecular Docking ◽

Interaction Network ◽

Network Pharmacology ◽

Potential Candidate ◽

Active Ingredients ◽

Protein Protein Interaction ◽

Pharmacological Mechanism ◽

Th17 Cell Differentiation ◽

The Relationship

Abstract Background: Ge-Gen-Qin-Lian Decoction (GGQLD), a traditional Chinese medicine (TCM) formula, has been widely used for ulcerative colitis (UC) in China, but the pharmacological mechanisms remain unclear. This research was designed to clarify the underlying pharmacological mechanism of GGQLD against UC. Method: In this research, a GGQLD-compound-target-UC network was constructed based on public databases to clarify the relationship between active compounds in GGQLD and potential targets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed to investigate biological functions associated with potential targets. A protein–protein interaction network was constructed to screen and evaluate hub genes and key active ingredients. Molecular docking was used to verify the activities of binding between hub targets and ingredients. Results: Finally, 83 potential therapeutic targets and 118 corresponding active ingredients were obtained by network pharmacology. Quercetin, kaempferol, wogonin, baicalein, and naringenin were identified as potential candidate ingredients. GO and KEGG enrichment analyses revealed that GGQLD had anti-inflammatory, antioxidative, and immunomodulatory effects. The effect of GGQLD on UC might be achieved by regulating the balance of cytokines (e.g., IL-6, TNF, IL-1β, CXCL8, CCL2) in the immune system and inflammation-related pathways, such as the IL-17 pathway and the Th17 cell differentiation pathway. In addition, molecular docking results demonstrated that the main active ingredient, quercetin, exhibited good affinity to hub targets. Conclusion: This research fully reflects the multicomponent and multitarget characteristics of GGQLD in the treatment of UC. Furthermore, the present study provided new insight into the mechanisms of GGQLD against UC.

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In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.665102 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaolu Liu ◽

Yuling Fan ◽

Lipeng Du ◽

Zhigang Mei ◽

Yang Fu

Keyword(s):

Ulcerative Colitis ◽

Molecular Docking ◽

Chinese Medicine ◽

In Silico ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Chronic Inflammatory Bowel Disease ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Tnf Α

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and Gegen Qinlian Decoction (GQD), a Chinese botanical formula, has exhibited beneficial efficacy against UC. However, the mechanisms underlying the effect of GQD still remain to be elucidated. In this study, network pharmacology approach and molecular docking in silico were applied to uncover the potential multicomponent synergetic effect and molecular mechanisms. The targets of ingredients in GQD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM) database, while the UC targets were retrieved from Genecards, therapeutic target database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The topological parameters of Protein-Protein Interaction (PPI) data were used to screen the hub targets in the network. The possible mechanisms were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the active compounds and hub targets. Network pharmacology analysis successfully identified 77 candidate compounds and 56 potential targets. The targets were further mapped to 20 related pathways to construct a compound-target-pathway network and an integrated network of GQD treating UC. Among these pathways, PI3K-AKT, HIF-1, VEGF, Ras, and TNF signaling pathways may exert important effects in the treatment of UC via inflammation suppression and anti-carcinogenesis. In the animal experiment, treatment with GQD and sulfasalazine (SASP) both ameliorated inflammation in UC. The proinflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by UC were significantly decreased by GQD and SASP. Moreover, the protein expression of EGFR, PI3K, and phosphorylation of AKT were reduced after GQD and SASP treatment, and there was no significance between the GQD group and SASP group. Our study systematically dissected the molecular mechanisms of GQD on the treatment of UC using network pharmacology, as well as uncovered the therapeutic effects of GQD against UC through ameliorating inflammation via downregulating EGFR/PI3K/AKT signaling pathway and the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6.

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Elucidating the Mechanisms of Action of Lianhua Qingwen decoction for the Treatment of COVID-19 via Systems Pharmacology Approaches

10.21203/rs.3.rs-21103/v2 ◽

2021 ◽

Author(s):

Xiting Wang ◽

Tao Lu

Keyword(s):

Molecular Docking ◽

Blood Circulation ◽

Interaction Network ◽

Enrichment Analysis ◽

Detection Algorithm ◽

Network Pharmacology ◽

Systems Pharmacology ◽

Protein Protein Interaction ◽

Further Development ◽

Protein Protein Interaction Network

Abstract Due to the severity of the COVID-19 epidemic, to identify a proper treatment for COVID-19 is of great significance. Traditional Chinese Medicine (TCM) has shown its great potential in the prevention and treatment of COVID-19. One of TCM decoction, Lianhua Qingwen decoction displayed promising treating efficacy. Nevertheless, the underlying molecular mechanism has not been explored for further development and treatment. Through systems pharmacology and network pharmacology approaches, we explored the potential mechanisms of Lianhua Qingwen treating COVID-19 and acting ingredients of Lianhua Qingwen decoction for COVID-19 treatment. Through this way, we generated an ingredients-targets database. We also used molecular docking to screen possible active ingredients. Also, we applied the protein-protein interaction network and detection algorithm to identify relevant protein groupings of Lianhua Qingwen. Totally, 605 ingredients and 1,089 targets were obtained. Molecular Docking analyses revealed that 35 components may be the promising acting ingredients, 7 of which were underlined according to the comprehensive analysis. Our enrichment analysis of the 7 highlighted ingredients showed relevant significant pathways that could be highly related to their potential mechanisms, e.g. oxidative stress response, inflammation, and blood circulation. In summary, this study suggests the promising mechanism of the Lianhua Qingwen decoction for COVID-19 treatment. Further experimental and clinical verifications are still needed.

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Mechanistic exploration of Cangfu Daotan Decoction for patients with polycystic ovary syndrome by transcriptome sequencing

10.21203/rs.3.rs-19780/v1 ◽

2020 ◽

Author(s):

Chunyue Chen ◽

Xuejuan Jiang ◽

Chenye Wang ◽

Caifei Ding

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Viral Gene Expression ◽

Enrichment Analysis ◽

Diabetic Mouse ◽

Viral Gene ◽

Ovary Syndrome ◽

Go Enrichment ◽

Medicine Prescription ◽

Chinese Medicine Prescription

Abstract Background Polycystic ovary syndrome (PCOS) is a common and complex female endocrine disorder. The pathogenesis of PCOS is not fully elucidated. Cangfu Daotan Decoction is a kind of traditional Chinese medicine prescription widely used for PCOS patients.Methods In this study, we treated two PCOS patients with Cangfu Daotan Decoction (CDD) and both patients presented favorable responses to the treatment. We performed RNA-seq to explore the underlying molecular mechanism.Results After data analysis, we found 4 differential expressed genes including S1PR1 , which has been found to be involved in islet β-cell proliferation and cell apoptosis in diabetic mouse models. We also identified 28 differential expressed transcripts including NFATC2 , CD14 and FCGR3A , which are involved in many immune processes.Conclusions After GO enrichment analysis, we found that pathways including viral gene expression and immune response are involved in the efficacy of CDD treatment. Our study provides new evidence to better understand the pathogenesis of PCOS.

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An Investigation of the Mechanism of Rapid Relief of Ulcerative Colitis Induced by Five-flavor Sophora Flavescens Enteric-coated Capsules Based on Network Pharmacology

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200302121711 ◽

2020 ◽

Vol 23 (3) ◽

pp. 239-252 ◽

Cited By ~ 1

Author(s):

Sizhen Gu ◽

Yan Xue ◽

Yuli Zhang ◽

Kanjun Chen ◽

Shigui Xue ◽

...

Keyword(s):

Ulcerative Colitis ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Immune Recognition ◽

Sophora Flavescens ◽

Active Components ◽

Pharmacological Mechanism ◽

The Core ◽

Correlation Parameters ◽

Enteric Coated

Aim and Objective: Five-Flavor Sophora flavescens Enteric-Coated Capsules (FSEC) are the only proprietary Chinese medicine approved for the treatment of ulcerative colitis (UC) in China. Phase II and III clinical trials have shown that the curative effect of FSEC in relieving UC was not inferior to that of mesalazine granules and enteric-coated tablets, but its pharmacological mechanism is unclear. Therefore, the network pharmacology is used to reveal the more comprehensive effective components and targets of FSEC in the treatment of UC. Methods: We screened the components of FSEC based on the TCMSP database, determined the action targets of these compounds through target fishing, and integrated the UC disease targets of several disease gene databases. The FSEC-UC composite targets were obtained by matching the two results, and then a PPI network was constructed to analyze the relationship between these targets, and the core targets were selected by topological correlation parameters. Finally, GO-BP and KEGG enrichment analyses were carried out using the clusterProfiler software package. Results: One hundred and sixty active components of FSEC were identified and 77 targets were obtained. Of these, 30 core targets were the main targets of FESC in the treatment of UC. And quercetin, kaempferol, luteolin and mangiferin were regarded as the core active components of FSEC. The results screened by GO and KEGG enrichment analysis showed that FSEC played a comprehensive therapeutic role in immune recognition, anti-inflammation and antioxidation mainly through IL-17, TNF, Toll-like receptor, NF-kappa B, and Th17 cell differentiation. Conclusion: The molecular mechanism of UC remission induced by FSEC was predicted by network pharmacology. These findings provide an important theoretical basis for further study of the effective substances and mechanism of FSEC in the treatment of UC.

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Analysis of the Molecular Mechanisms of the Effects of Prunella vulgaris against Subacute Thyroiditis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9810709 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Xin Shen ◽

Rui Yang ◽

Jianpeng An ◽

Xia Zhong

Keyword(s):

Signaling Pathways ◽

Molecular Mechanisms ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Subacute Thyroiditis ◽

Network Pharmacology ◽

Pharmacokinetic Parameters ◽

Pathway Enrichment Analysis ◽

Prunella Vulgaris ◽

Protein Protein Interaction

Prunella vulgaris (PV) has a long history of application in traditional Chinese and Western medicine as a remedy for the treatment of subacute thyroiditis (SAT). This study applied network pharmacology to elucidate the mechanism of the effects of PV against SAT. Components of the potential therapeutic targets of PV and SAT-related targets were retrieved from databases. To construct a protein-protein interaction (PPI) network, the intersection of SAT-related targets and PV-related targets was input into the STRING platform. Gene ontology (GO) analysis and KEGG pathway enrichment analysis were carried out using the DAVID database. Networks were constructed by Cytoscape for visualization. The results showed that a total of 11 compounds were identified according to the pharmacokinetic parameters of ADME. A total of 126 PV-related targets and 2207 SAT-related targets were collected, and 83 overlapping targets were subsequently obtained. The results of the KEGG pathway and compound-target-pathway (C-T-P) network analysis suggested that the anti-SAT effect of PV mainly occurs through quercetin, luteolin, kaempferol, and beta-sitosterol and is most closely associated with their regulation of inflammation and apoptosis by targeting the PIK3CG, MAPK1, MAPK14, TNF, and PTGS2 proteins and the PI3K-Akt and TNF signaling pathways. The study demonstrated that quercetin, luteolin, kaempferol, and beta-sitosterol in PV may play a major role in the treatment of SAT, which was associated with the regulation of inflammation and apoptosis, by targeting the PI3K-Akt and TNF signaling pathways.

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A Network Pharmacology Approach to Uncover the Mechanisms of Shen-Qi-Di-Huang Decoction against Diabetic Nephropathy

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/7043402 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 9

Author(s):

Sha Di ◽

Lin Han ◽

Qing Wang ◽

Xinkui Liu ◽

Yingying Yang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Interaction Network ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Protein Protein Interaction ◽

Regulation Of Blood Pressure ◽

Protein Protein Interaction Network

Shen-Qi-Di-Huang decoction (SQDHD), a well-known herbal formula from China, has been widely used in the treatment of diabetic nephropathy (DN). However, the pharmacological mechanisms of SQDHD have not been entirely elucidated. At first, we conducted a comprehensive literature search to identify the active constituents of SQDHD, determined their corresponding targets, and obtained known DN targets from several databases. A protein-protein interaction network was then built to explore the complex relations between SQDHD targets and those known to treat DN. Following the topological feature screening of each node in the network, 400 major targets of SQDHD were obtained. The pathway enrichment analysis results acquired from DAVID showed that the significant bioprocesses and pathways include oxidative stress, response to glucose, regulation of blood pressure, regulation of cell proliferation, cytokine-mediated signaling pathway, and the apoptotic signaling pathway. More interestingly, five key targets of SQDHD, named AKT1, AR, CTNNB1, EGFR, and ESR1, were significant in the regulation of the above bioprocesses and pathways. This study partially verified and predicted the pharmacological and molecular mechanisms of SQDHD on DN from a holistic perspective. This has laid the foundation for further experimental research and has expanded the rational application of SQDHD in clinical practice.

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Study on the Effective Material Basis and Mechanism of Traditional Chinese Medicine Prescription (QJC) Against Stress Diarrhea in Mice

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.724491 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yuefeng Zhang ◽

Fei Yu ◽

Jingyou Hao ◽

Eliphaz Nsabimana ◽

Yanru Wei ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Pathological Condition ◽

Akt Signaling ◽

Network Pharmacology ◽

Akt Signaling Pathway ◽

Expression Levels ◽

Medicine Prescription ◽

Chinese Medicine Prescription

Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Astragalus propinquus Schischkin (HQ), Zingiber officinale Roscoe (SJ), and Plantago asiatica L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and in vivo experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)–Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K–Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of PI3K and Akt, inhibited the expression of phosphatase and tensin homolog (PTEN), and activated the PI3K–Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of PI3K and Akt and inhibiting the expression levels of PTEN.

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Investigating the Mechanism of Guizhi Fuling Formula in the Treatment of Primary Dysmenorrhea based on Network Pharmacology and Molecular Docking

10.21203/rs.3.rs-151904/v1 ◽

2021 ◽

Author(s):

Lu Sun ◽

Zining Wang ◽

Jian Li ◽

Li Xu ◽

Xiaoou Xue

Keyword(s):

Molecular Docking ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Primary Dysmenorrhea ◽

Potential Mechanism ◽

Protein Protein Interaction ◽

Long Time ◽

Hormone Biosynthesis ◽

Relationship Of

Abstract Background: Primary dysmenorrhea(PD)is the most common gynecologic disorder.Despite the prevalence is high, it is often underdiagnosed,undertreated and normalized even by patients themselves. Guizhi Fuling Formula (GFF) is experientially used for the treatment of PD in a long time. Therefore, the efficiency and potential mechanism are waiting to identify.Methods: We adopted network pharmacology integrated molecular docking strategy in this study.Based on published literatures, the relative compounds of GFF were selected preliminarily. Secondly, the putative targets of PD were obtained by wide-searching DisGeNET, OMIM, Drugbank and GeneCards databases.With protein-protein interaction(PPI) analysis, GO and KEGG pathway enrichment analysis and molecular docking ,we systematically evaluated the relationship of herb ingredients and disease targets.Results: The results showed that 30 ingredients of GFF and 43 hub targets made a difference.Under the further analysis,8 targets(EGFR,AKT1,PTGS2,TNF,ESR1,AHR,CTNNB1,CXCL8) were recognized as key therapeutic targets with excellent binding. The enrichment analyses indicated that the GFF had the potential to influence varieties of biological pathways, especially the pathways in cancer and steroid hormone biosynthesis, which play an important part in the pathogenesis of primary dysmenorrhea.Conclusion: GFF influenced primary dysmenorrhea through the synergistic effect of multiple components, multiple targets, and multiple pathways.This study predictedthe potential mechanism, hope that could made contribution for clinical application and scientific research.

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Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Dextran Sodium Sulfate-Induced Ulcerative Colitis

10.1101/2021.09.28.462065 ◽

2021 ◽

Author(s):

Desheng Hu ◽

Mingyue Li ◽

Weina Guo ◽

Yalan Dong ◽

Wenzhu Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Protective Effect ◽

Intestinal Permeability ◽

Chronic Inflammatory Bowel Disease ◽

Protective Mechanism ◽

Therapeutic Effects ◽

Dependent Manner ◽

Colonic Inflammation ◽

Anti Inflammatory

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by multi-factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that Celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and the mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR preforms the protective effect. We characterized the therapeutic effects and the potential mechanism of CSR in treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation approaches. CSR administration significantly ameliorated DSS-induced colitis, as evidenced by the recovery of body weight and colon length, decreased disease activity index (DAI) score, as well as decreased intestinal permeability. CSR down-regulated the secretion of proinflammatory cytokines, upregulated the anti-inflammatory mediators, and improved the balances of Treg/Th1 and Treg/Th17 to maintain colonic immune homeostasis. However, the protective effects of CSR disappeared when the antibiotic cocktail was applied to deplete the gut microbiota, and the gut microbiota-mediated effect was confirmed by FMT. Furthermore, CSR treatment increased the gut microbiota diversity and composition, and raised the metabolic productions of pyruvate and adenosine, which probably involve in gut microbiota mediated protective effect. In conclusion, CSR ameliorates colonic inflammation in a gut microbiota-dependent manner. The underlying protective mechanism is associated with the rectified Treg/Th1 and Treg/Th17 balance, and increased pyruvate and adenosine production. The study provided the solid evidence that CSR might be a promising therapeutic drug for UC.

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