Revealing the Pharmacological Mechanism of Acorus tatarinowii in the Treatment of Ischemic Stroke Based on Network Pharmacology

Aim. Stroke is the second significant cause for death, with ischemic stroke (IS) being the main type threatening human being’s health. Acorus tatarinowii (AT) is widely used in the treatment of Alzheimer disease, epilepsy, depression, and stroke, which leads to disorders of consciousness disease. However, the systemic mechanism of AT treating IS is unexplicit. This article is supposed to explain why AT has an effect on the treatment of IS in a comprehensive and systematic way by network pharmacology. Methods and Materials. ADME (absorbed, distributed, metabolized, and excreted) is an important property for screening-related compounds in AT, which were screening out of TCMSP, TCMID, Chemistry Database, and literature from CNKI. Then, these targets related to screened compounds were predicted via Swiss Targets, when AT-related targets database was established. The gene targets related to IS were collected from DisGeNET and GeneCards. IS-AT is a common protein interactive network established by STRING Database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analysed by IS-AT common target genes. Cytoscape software was used to establish a visualized network for active compounds-core targets and core target proteins-proteins interactive network. Furthermore, we drew a signal pathway picture about its effect to reveal the basic mechanism of AT against IS systematically. Results. There were 53 active compounds screened from AT, inferring the main therapeutic substances as follows: bisasaricin, 3-cyclohexene-1-methanol-α,α,4-trimethyl,acetate, cis,cis,cis-7,10,13-hexadecatrienal, hydroxyacoronene, nerolidol, galgravin, veraguensin, 2′-o-methyl isoliquiritigenin, gamma-asarone, and alpha-asarone. We obtained 398 related targets, 63 of which were the same as the IS-related genes from targets prediction. Except for GRM2, remaining 62 target genes have an interactive relation, respectively. The top 10 degree core target genes were IL6, TNF, IL1B, TLR4, NOS3, MAPK1, PTGS2, VEGFA, JUN, and MMP9. There were more than 20 terms of biological process, 7 terms of cellular components, and 14 terms of molecular function through GO enrichment analysis and 13 terms of signal pathway from KEGG enrichment analysis based on P < 0.05 . Conclusion. AT had a therapeutic effect for ischemic via multicomponent, multitarget, and multisignal pathway, which provided a novel research aspect for AT against IS.

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Network Pharmacology Identifies the Mechanisms of Action of Tongxie Anchang Decoction in the Treatment of Irritable Bowel Syndrome with Diarrhea Predominant

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2723705 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Xiang Tan ◽

Wenjing Pei ◽

Chune Xie ◽

Zhibin Wang ◽

Tangyou Mao ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Target Genes ◽

Alternative Therapy ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Active Compounds ◽

Complementary And Alternative Therapy ◽

Pharmacological Mechanism ◽

Target Network ◽

Irritable Bowel

Aim. This study aims to uncover the pharmacological mechanism of Tongxie Anchang Decoction (TXACD), a new and effective traditional Chinese medicine (TCM) prescription, for treating irritable bowel syndrome with diarrhea predominant (IBS-D) using network pharmacology. Methods. The active compounds and putative targets of TXACD were retrieved from TCMSP database and published literature; related target genes of IBS-D were retrieved from GeneCards; PPI network of the common target hub gene was constructed by STRING. Furthermore, these hub genes were analyzed using gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results. A total of 54 active compounds and 639 targets were identified through a database search. The compound-target network was constructed, and the key compounds were screened out according to the degree. By using the PPI and GO and KEGG enrichment analyses, the pharmacological mechanism network of TXACD in the treatment of IBS-D was constructed. Conclusions. This study revealed the possible mechanisms by which TXACD treatment alleviated IBS-D involvement in the modulation of multiple targets and multiple pathways, including the immune regulation, inflammatory response, and oxidative stress. These findings provide novel insights into the regulatory role of TXACD in the prevention and treatment of IBS-D and hold promise for herb-based complementary and alternative therapy.

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Exploring the Pharmacological Mechanism of Cassiae Semen a Cting on Cataracts Based on a Network Pharmacology Approach

10.21203/rs.3.rs-90766/v1 ◽

2020 ◽

Author(s):

Ying Zhong ◽

Youfa Fang

Keyword(s):

Signaling Pathway ◽

Target Genes ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Network Pharmacology ◽

Active Compounds ◽

Pharmacological Mechanism ◽

Ppi Networks ◽

Target Network ◽

Central Network

Abstract BackgroundCassiae Semen (CS) is one of the most well-known herbs used in the treatment of cataracts in China. However, the potential mechanisms of its anti-cataracts effects have not been fully explored.MethodThe active compounds of CS were obtained from TCMSP database, and their targets were retrieved from the TCMSP, STITCH and DrugBank databases. Cataracts related target genes were identified from the GeneCard, Malacard, and OMIM databases. GO and KEGG analysis were performed using DAVID online tools, and Cytoscape were used to construct compound-targets network and protein-protein interaction (PPI) networks, cluster analysis were carried out using MCODE plugin for Cytoscape.ResultsWe obtained 13 active compounds from CS and 105 targets in total to construct a compound-target network, which indicated that emodin, stigmastero, and rhein served as the main ingredients in CS. A total of 238 cataracts related targets were identified from public databases. PPI networks of compound targets and cataract-related targets were constructed and merged to obtained the central network, enrichment analysis showed 50 key targets in the central network enriched in several important signaling pathways, such as thyroid hormone signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway. The top 4 genes with higher degree in the central network were TP53, HSP90, ESR1, EGFR, indicating their important roles in the treatment of cataracts.ConclusionsThe present study systematically revealed the multi-target mechanisms of CS on cataracts using network pharmacology approach, and provided indications for further mechanistic studies and also for the development of CS as a potential treatment for cataracts patients.

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A Network Pharmacology Approach to Explore the Pharmacological Mechanism of Xiaoyao Powder on Anovulatory Infertility

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/2960372 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 22

Author(s):

Huiping Liu ◽

Liuting Zeng ◽

Kailin Yang ◽

Guomin Zhang

Keyword(s):

Enrichment Analysis ◽

Network Pharmacology ◽

Signal Pathways ◽

Active Compounds ◽

Pharmacological Mechanism ◽

Go Enrichment ◽

Human Proteins ◽

Network Pictures ◽

Go Enrichment Analysis ◽

Anovulatory Infertility

Aim.To explore the pharmacological mechanism of Xiaoyao powder (XYP) on anovulatory infertility by a network pharmacology approach.Method.Collect XYP’s active compounds by traditional Chinese medicine (TCM) databases, and input them into PharmMapper to get their targets. Then note these targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and filter out targets that can be noted by human signal pathway. Get the information of modern pharmacology of active compounds and recipe’s traditional effects through databases. Acquire infertility targets by Therapeutic Target Database (TTD). Collect the interactions of all the targets and other human proteins via String and INACT. Put all the targets into the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to do GO enrichment analysis. Finally, draw the network by Cytoscape by the information above.Result.Six network pictures and two GO enrichment analysis pictures are visualized.Conclusion.According to this network pharmacology approach some signal pathways of XYP acting on infertility are found for the first time. Some biological processes can also be identified as XYP’s effects on anovulatory infertility. We believe that evaluating the efficacy of TCM recipes and uncovering the pharmacological mechanism on a systematic level will be a significant method for future studies.

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Deciphering the Key Pharmacological Pathways and Targets of Yisui Qinghuang Powder That Acts on Myelodysplastic Syndromes Using a Network Pharmacology-Based Strategy

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8877295 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Zijian Han ◽

Luping Song ◽

Kele Qi ◽

Yang Ding ◽

Mingjun Wei ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Target Genes ◽

Network Pharmacology ◽

Analysis Tool ◽

Antitumor Effects ◽

Active Compounds ◽

Pharmacological Mechanism ◽

Putative Target ◽

Target Disease ◽

Qinghuang Powder

Background. Yisui Qinghuang powder (YSQHP) is an effective traditional Chinese medicinal formulation used for the treatment of myelodysplastic syndromes (MDS). However, its pharmacological mechanism of action is unclear. Materials and Methods. In this study, the active compounds of YSQHP were screened using the traditional Chinese medicine systems pharmacology (TCMSP) and HerDing databases, and the putative target genes of YSQHP were predicted using the STITCH and DrugBank databases. Then, we further screened the correlative biotargets of YSQHP and MDS. Finally, the compound-target-disease (C-T-D) network was conducted using Cytoscape, while GO and KEGG analyses were conducted using R software. Furthermore, DDI-CPI, a web molecular docking analysis tool, was used to verify potential targets and pathways. Finally, binding site analysis was performed to identify core targets using MOE software. Results. Our results identified 19 active compounds and 273 putative target genes of YSQHP. The findings of the C-T-D network revealed that Rb1, CASP3, BCL2, and MAPK3 showed the most number of interactions, whereas indirubin, tryptanthrin, G-Rg1, G-Rb1, and G-Rh2 showed the most number of potential targets. The GO analysis showed that 17 proteins were related with STPK activity, PUP ligase binding, and kinase regulator activity. The KEGG analysis showed that PI3K/AKT, apoptosis, and the p53 pathways were the main pathways involved. DDI-CPI identified the top 25 proteins related with PI3K/AKT, apoptosis, and the p53 pathways. CASP8, GSK3B, PRKCA, and VEGFR2 were identified as the correlative biotargets of DDI-CPI and PPI, and their binding sites were found to be indirubin, G-Rh2, and G-Rf. Conclusion. Taken together, our results revealed that YSQHP likely exerts its antitumor effects by binding to CASP8, GSK3B, PRKCA, and VEGFR2 and by regulating the apoptosis, p53, and PI3K/AKT pathways.

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Network Pharmacology Analysis of the active components and anticancer targets of Rhubarb

10.1101/2021.01.28.428583 ◽

2021 ◽

Author(s):

Hu Junrui ◽

Duan Yongqiang ◽

Cui Gongning ◽

Luo Qiang ◽

Xi Shanshan ◽

...

Keyword(s):

Pathway Analysis ◽

Drug Targets ◽

Target Genes ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Active Components ◽

Active Compounds ◽

Cellular Targets ◽

Kegg Pathway Analysis

AbstractTo investigate the mechanisms and active components governing the anticancer activity of rhubarb.The TCMSP database was screened to identify the active components of rhubarb and Swiss target predictions were generated to predict their cellular targets. TTD and OMIM databases were used to predict tumor-related target genes. "Cytoscape" was used to construct drug targets. PPI network analysis, GO enrichment analysis and KEGG pathway analysis of the key targets were investigated using String and David databases. A total of 33 components and 116 corresponding targets were screened. Amongst them, the key active compounds in rhubarb included emodin, aloe emodin, β-sitosterol, emodin methyl ether and rhein, which were predicted to target TP53, AKT1, STAT3, PIK3CA, HRAS, and VEGFA. GO analysis revealed that the cellular targets clustered into 159 biological processes, including those involved in cellular composition (n=24) and molecular functions (n=42, P<0.01). KEGG pathway analysis revealed 85 (P < 0.01) pathways related to cancer. The active compounds in rhubarb target TP53, AKT1 and PIK3CA. Rhubarb therefore regulates cancer development through an array of biological pathways.

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Study on the Anti-Tumor Mechanism and Target of Triptolide based on Network Pharmacology and Molecular Docking

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892816666210211143059 ◽

2021 ◽

Vol 16 ◽

Author(s):

Tao Zou ◽

Yuanqiong Huang ◽

Yifan Hu ◽

Mingyu Wu ◽

Yueshui Zhao ◽

...

Keyword(s):

Target Genes ◽

Inflammatory Responses ◽

Tumor Development ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Specific Target ◽

Pharmacological Mechanism ◽

The Core ◽

Core Genes

Background: According to the special physiological and pharmacological activities of natural compounds, many drugs with special therapeutic effects have been developed. The triptolide (TP) is a kind of natural anti-tumor drug with a world patent, but its target and mechanism are yet not known. Objective: The study aims to explore and predict the target and mechanism of TP on non-small cell lung cancer (NSCLC), pancreatic cancer (PC) and colorectal cancer (CC) through network pharmacology technology. Methods: We screened the core targets of TP with NSCLC, PC and CC, respectively, and carried out network analysis, enrichment analysis and ligand-receptor docking to clarify its potential pharmacological mechanism. Results: By screening the core genes between TP with NSCLC, PC and CC, respectively, it was found that PTGS2 was the common target gene in the three cancers. NSCLC, CCL2, IL6, HMOX1 and COL1A1 are the specific target genes, while MMP2, JUN, and CXCL8 are the specific target genes in PC. In CC, the specific target genes includeERBB2, VEGFA, STAT1 andMAPK8. In enrichment analysis, it was found that the NF- κB, toll-like receptors and IL-17 signaling pathway were mainly involved in TP for these cancers. The binding energy of TP to the core target is less than that of cyclophosphamide. Conclusions: This study preliminarily revealed that TP may prevent and treat cancers\ through multiple targets and pathways. The possible mechanisms of TP include regulating immune and inflammatory responses, promoting apoptosis and inhibiting tumor development. It shows that TP may have a potential in treating kinds of tumors.

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Network Pharmacology Reveals the Molecular Mechanism of Cuyuxunxi Prescription in Promoting Wound Healing in Patients with Anal Fistula

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/3865121 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Yin Qu ◽

Zhijun Zhang ◽

Yafeng Lu ◽

De Zheng ◽

Yang Wei

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Target Genes ◽

Herbal Medicines ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Network Pharmacology ◽

Surgical Wound ◽

Active Compounds

Background. The healing process of the surgical wound of anal fistulotomy is much slower because of the presence of stool within the wound. Cuyuxunxi (CYXX) prescription is a Chinese herbal fumigant that is being used to wash surgical wound after anal fistulotomy. This study aimed at investigating the molecular mechanism of CYXX prescription using a network pharmacology-based strategy. Materials and Methods. The active compounds in each herbal medicine were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and in Traditional Chinese Medicine Integrated Database (TCMID) analysis platform based on the criteria of oral bioavailability ≥40% and drug-likeness ≥0.2. The disease-related target genes were extracted from the Comparative Toxicogenomics Database. Protein-protein interaction network was built for the overlapped genes as well as functional enrichment analysis. Finally, an ingredient-target genes-pathway network was built by integrating all information. Results. A total of 375 chemical ingredients of the 5 main herbal medicines in CYXX prescription were retrieved from TCMSP database and TCMID. Among the 375 chemical ingredients, 59 were active compounds. Besides, 325 target genes for 16 active compounds in 3 herbal medicines were obtained. Functional enrichment analysis revealed that these overlapped genes were significantly related with immune response, biosynthesis of antibiotics, and complement and coagulation cascades. A comprehensive network which contains 133 nodes (8 disease nodes, 3 drug nodes, 8 ingredients, 103 target gene nodes, 7 GO nodes, and 4 pathway nodes) was built. Conclusion. The network built in this study might aid in understanding the action mechanism of CYXX prescription at molecular level to pathway level.

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A Network Pharmacology Approach to Investigate the Active Compounds and Mechanisms of Musk for Ischemic Stroke

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4063180 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Changlin Zhang ◽

Yingdi Liao ◽

Lingling Liu ◽

Yifan Sun ◽

Shaoqin Lin ◽

...

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Cell Receptor ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Chemical Components ◽

Pathway Enrichment Analysis ◽

Active Compounds ◽

And Cluster Analysis

Objectives. This study aims to study the material basis and effective mechanism of musk for ischemic stroke (IS) based on the network pharmacology approach. Methods. We collected the chemical components and target gene of musk from the BATMAN-TCM analytical platform and identified ischemic stroke-related targets from the following databases: DisGeNET, NCBI-Gene, HPO, OMIM, DrugBank, and TTD. The targets of musk and IS were uploaded to the String database to construct the protein-protein interaction (PPI) network, and then, the key targets were analyzed by topological methods. At last, the function biological process and signaling pathways of key targets were carried out by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and cluster analysis by using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server and Metascape platform. Results. A total of 29 active compounds involving 1081 predicted targets were identified in musk and there were 1104 IS-related targets. And 88 key targets of musk for IS were obtained including AKT1, MAPK1/3, TP53, TNF, SRC, FOS, CASP3, JUN, NOS3, and IL1B. The GO and KEGG enrichment analysis suggested that these key targets are mainly involved in multiple pathways which participated in TNF signaling pathway, estrogen signaling pathway, prolactin signaling pathway, neurotrophin signaling pathway, T-cell receptor signaling pathway, cAMP signaling pathway, FoxO signaling pathway, and HIF1 signaling pathway. Conclusion. This study revealed that the effective mechanisms of musk against IS would be associated with the regulation of apoptosis, inflammatory response, and gene transcription.

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Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8215454 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Yihui Feng ◽

Xinyi Chai ◽

Yingyin Chen ◽

Yan Ning ◽

Ying Zhao

Keyword(s):

Molecular Docking ◽

Chinese Medicine ◽

Glucose Metabolism ◽

Target Genes ◽

Premature Ovarian Insufficiency ◽

Network Pharmacology ◽

Biological Processes ◽

Ovarian Insufficiency ◽

Active Compounds ◽

Pharmacological Mechanism

Background and Purpose. Premature ovarian insufficiency (POI) is a serious reproductive disease in females that is characterized by menstrual and ovulation disorders and infertility. The clinical efficacy of complementary and alternative medicine (CAM) has been reported in POI, including compound Chinese medicine. Zishen Yutai Pills (ZSYTP), a well-known patented Chinese medicine, has been widely used for treating POI; however, the pharmacological mechanism and molecular targets of ZSYTP remain unknown. Here, we systematically elucidated the pharmacological mechanism of ZSYTP on POI using a network pharmacology approach and further validated our findings with molecular docking. Methods. A comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking. Results. A total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized. Conclusion. Intriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.

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Molecular Mechanism of The Effect of Huanglian Jiedu Decoction On Ulcerative Colitis Based On Network Pharmacology And Molecular Docking

10.21203/rs.3.rs-807332/v1 ◽

2021 ◽

Author(s):

Jing Yang ◽

Chao-Tao Tang ◽

Ruiri Jin ◽

Bixia Liu ◽

Peng Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Molecular Docking ◽

Molecular Mechanism ◽

Target Genes ◽

Signal Pathway ◽

Intestinal Barrier Function ◽

Network Pharmacology ◽

Bioactive Components ◽

Ppi Network ◽

Active Components

Abstract Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC by means of network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are considered to be very important to PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had good affinity with Hub gene. This study systematically elucidates the "multi-component, multi-target, multi-pathway" mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.

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