Investigating the Biomarkers of the Sasang Constitution via Network Pharmacology Approach

Sasang constitutional (SC) medicine classifies people into Soeum (SE), Soyang (SY), Taeeum (TE), and Taeyang (TY) types based on psychological and physical traits. However, biomarkers of these types are still unclear. We aimed to identify biomarkers among the SC types using network pharmacology methods. Target genes associated with the SC types were identified by grouping herb targets that preserve and strengthen the requisite energy (Bomyeongjiju). The herb targets were obtained by constructing an herb-compound-target network. We identified 371, 185, 146, and 89 target genes and their unique biological processes related to SE, SY, TE, and TY types, respectively. While the targets of SE and SY types were the most similar among the target pairs of the SC types, those of TY type overlapped with only a few other SC-type targets. Moreover, SE, SY, TE, and TY were related to “diseases of the digestive system,” “diseases of the nervous system,” “endocrine, nutritional, and metabolic diseases,” and “congenital malformations, deformations, and chromosomal abnormalities,” respectively. We successfully identified the target genes, biological processes, and diseases related to each SC type. We also demonstrated that a drug-centric approach using network pharmacology analysis provides a deeper understanding of the concept of Sasang constitutional medicine at a phenotypic level.

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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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Systems Pharmacological Approach to the Effect of Bulsu-san Promoting Parturition

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/7236436 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 5

Author(s):

Su Yeon Suh ◽

Won G. An

Keyword(s):

Analytical Approach ◽

Target Genes ◽

Clinical Applications ◽

Oriental Medicine ◽

Biological Processes ◽

Gene Ontology Analysis ◽

Multiple Target ◽

Pathway Network ◽

Target Network ◽

Compound Target

Bulsu-san (BSS) has been commonly used in oriental medicine for pregnant women in East Asia. The purpose of this research was to elucidate the effect of BSS on ease of parturition using a systems-level in silico analytic approach. Research results show that BSS is highly connected to the parturition related pathways, biological processes, and organs. There were numerous interactions between most compounds of BSS and multiple target genes, and this was confirmed using herb-compound-target network, target-pathway network, and gene ontology analysis. Furthermore, the mRNA expression of relevant target genes of BSS was elevated significantly in related organ tissues, such as those of the uterus, placenta, fetus, hypothalamus, and pituitary gland. This study used a network analytical approach to demonstrate that Bulsu-san (BSS) is closely related to the parturition related pathways, biological processes, and organs. It is meaningful that this systems-level network analysis result strengthens the basis of clinical applications of BSS on ease of parturition.

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A landscape for drug-target interactions based on network analysis

PLoS ONE ◽

10.1371/journal.pone.0247018 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247018

Author(s):

Edgardo Galan-Vasquez ◽

Ernesto Perez-Rueda

Keyword(s):

Drug Target ◽

Target Genes ◽

Metabolic Diseases ◽

Drug Repositioning ◽

Topological Analysis ◽

Interaction Network ◽

Clustering Coefficient ◽

Connected Components ◽

Target Interaction ◽

Target Network

In this work, we performed an analysis of the networks of interactions between drugs and their targets to assess how connected the compounds are. For our purpose, the interactions were downloaded from the DrugBank database, and we considered all drugs approved by the FDA. Based on topological analysis of this interaction network, we obtained information on degree, clustering coefficient, connected components, and centrality of these interactions. We identified that this drug-target interaction network cannot be divided into two disjoint and independent sets, i.e., it is not bipartite. In addition, the connectivity or associations between every pair of nodes identified that the drug-target network is constituted of 165 connected components, where one giant component contains 4376 interactions that represent 89.99% of all the elements. In this regard, the histamine H1 receptor, which belongs to the family of rhodopsin-like G-protein-coupled receptors and is activated by the biogenic amine histamine, was found to be the most important node in the centrality of input-degrees. In the case of centrality of output-degrees, fostamatinib was found to be the most important node, as this drug interacts with 300 different targets, including arachidonate 5-lipoxygenase or ALOX5, expressed on cells primarily involved in regulation of immune responses. The top 10 hubs interacted with 33% of the target genes. Fostamatinib stands out because it is used for the treatment of chronic immune thrombocytopenia in adults. Finally, 187 highly connected sets of nodes, structured in communities, were also identified. Indeed, the largest communities have more than 400 elements and are related to metabolic diseases, psychiatric disorders and cancer. Our results demonstrate the possibilities to explore these compounds and their targets to improve drug repositioning and contend against emergent diseases.

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A network pharmacology-based approach to explore potential targets of Caesalpinia pulcherima: an updated prototype in drug discovery

Scientific Reports ◽

10.1038/s41598-020-74251-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Nikhil S. Sakle ◽

Shweta A. More ◽

Santosh N. Mokale

Keyword(s):

Breast Cancer ◽

Target Genes ◽

Docking Study ◽

Network Pharmacology ◽

Egfr Expression ◽

Target Network ◽

Anti Fungal ◽

Compound Target

Abstract Caesalpinia pulcherima (CP) is a traditional herb used for the treatment of asthma, bronchitis, cancer, anti-bacterial, anti-fungal and as abortifacient. In the present study, bioactive components and potential targets in the treatment of breast cancer validated through in silico, in vitro and in vivo approach. The results for the analysis were as among 29 components, only four components were found active for further study which proved the use of CP as a multi-target herb for betterment of clinical uses. The results found by PPI states that our network has significant interactions which include the ESR-1, ESR-2, ESRRA, MET, VEGF, FGF, PI3K, PDK-1, MAPK, PLK-1, NEK-2, and GRK. Compound-target network involves 4 active compound and 150 target genes which elucidate the mechanisms of drug action in breast cancer treatment. Furthermore, on the basis of the above results the important proteins were fetched for the docking study which helps in predicting the possible interaction between components and targets. The results of the western blotting showed that CP regulates ER and EGFR expression in MCF-7 cell. In addition to this animal experimentation showed that CP significantly improved immunohistological status in MNU induced carcinoma rats. Network pharmacology approach not only helps us to confirm the study of the chosen target but also gave an idea of compound-target network as well as pathways associated to the CP for treating the complex metabolic condition as breast cancer and they importance for experimental verification.

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The molecular mechanism of TiaoGanYiPi formula for treatment of chronic hepatitis B by network pharmacology and molecular docking verification

10.21203/rs.3.rs-120141/v1 ◽

2020 ◽

Author(s):

Xu Cao ◽

Xiaobin Zao ◽

Baiquan Xue ◽

Hening Chen ◽

Jiaxin Zhang ◽

...

Keyword(s):

Chronic Hepatitis ◽

Molecular Docking ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Target Genes ◽

Regulation Of Gene Expression ◽

Interaction Network ◽

Network Pharmacology ◽

Biological Processes ◽

The Relationship

Abstract The Chinese herbal formula Tiao-Gan-Yi-Pi (TGYP) showed effective against Chronic Hepatitis B (CHB). In this study, we aimed to clarify the mechanisms and potential targets between TGYP and CHB through network pharmacology and molecular docking verification. The compounds of TGYP were identified in the TCMSP and CNKI databases, and their putative targets were predicted through SwissTargetPrediction and STITCH databases. The targets of CHB were obtained from the GeneCards, NCBI Gene, and DisGeNET databases. The above mentioned data were visualized using Cytoscape, and molecular docking showed the relationship between them. The expression of key targets was verified in GEO databases. Hence, we screened out 11 TGYP-related key targets for CHB included ABL1, CASP8, CCNA2, CCNB1, CDK4, CDKN1A, EP300, HIF1A, IGF1R, MAP2K1 and PGR. The key targets were predominantly enriched in the cancer, cell cycle and hepatitis B pathways and involved in the positive regulation of fibroblast proliferation, signal transduction, and negative regulation of gene expression biological processes, and expression of key target genes was related to HBV infection and liver inflammation. Through this newly constructed interaction network between TGYP and CHB, we identified active compounds and targets which could be further used for providing clinical guidance.

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Network Pharmacology Strategy to Investigate the Pharmacological Mechanism of Siwu Decoction on Primary Dysmenorrhea and Molecular Docking Verification

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6662247 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Dandan Jiang ◽

Xiaoyan Wang ◽

Lijun Tian ◽

Yufeng Zhang

Keyword(s):

Molecular Docking ◽

Target Genes ◽

Network Pharmacology ◽

Primary Dysmenorrhea ◽

Ppi Network ◽

Active Compounds ◽

Docking Simulations ◽

Active Target ◽

Target Network ◽

Compound Target

Objective. To study the pharmacological mechanisms of Siwu decoction (SWD) on primary dysmenorrhea (PDM) and verify with molecular docking. Methods. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilized to acquire the active compounds and their corresponding target genes. The GeneCards database was utilized in the search for target genes that were associated with PDM. The intersection genes from the active target genes of SWD and those associated with PDM represented the active target genes of SWD that act on PDM. The Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were both carried out by RGUI 3.6.1 and Cytoscape 3.6.0 software. Cytoscape was also utilized for creating a compound-target network, and a protein-protein interaction (PPI) network was created through the STRING database. Molecular docking simulations of the macromolecular protein target receptors and their corresponding compounds were performed using AutoDockTool 1.5.6 and AutoDock Vina software. Results. We identified 14 active compounds as well as 97 active target genes of SWD by using the TCMSP. We compared the 97 active target genes of SWD to the 299 target genes related to PDM, and 23 active target genes for SWD that act on PDM which correlated with 11 active compounds were detected. The compound-target network as well as the PPI network were created, in addition to selecting the most essential compounds and their targets in order to create a key compound-target network. The most essential compounds were kaempferol, beta-sitosterol, stigmasterol, and myricanone. The key targets were AKT1, PTGS2, ESR1, AHR, CASP3, and PGR. Lastly, molecular docking was used to confirm binding of the target with its corresponding compound. Conclusion. The pharmacological mechanisms of SWD that act on PDM were investigated, and the active compounds in the SWD for treating PDM were further verified.

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Deciphering the Molecular Targets and Mechanisms of HGWD in the Treatment of Rheumatoid Arthritis via Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/7151634 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Wei Liu ◽

Yihua Fan ◽

Chunying Tian ◽

Yue Jin ◽

Shaopeng Du ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Signaling Pathway ◽

Differentially Expressed Genes ◽

Target Genes ◽

Differentially Expressed ◽

Network Pharmacology ◽

Active Compounds ◽

Target Proteins ◽

Target Network

Background. Huangqi Guizhi Wuwu Decoction (HGWD) has been applied in the treatment of joint pain for more than 1000 years in China. Currently, most physicians use HGWD to treat rheumatoid arthritis (RA), and it has proved to have high efficacy. Therefore, it is necessary to explore the potential mechanism of action of HGWD in RA treatment based on network pharmacology and molecular docking methods. Methods. The active compounds of HGWD were collected, and their targets were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and DrugBank database, respectively. The RA-related targets were retrieved by analyzing the differentially expressed genes between RA patients and healthy individuals. Subsequently, the compound-target network of HGWD was constructed and visualized through Cytoscape 3.8.0 software. Protein-protein interaction (PPI) network was constructed to explore the potential mechanisms of HGWD on RA using the plugin BisoGenet of Cytoscape 3.8.0 software. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed in R software (Bioconductor, clusterProfiler). Afterward, molecular docking was used to analyze the binding force of the top 10 active compounds with target proteins of VCAM1, CTNNB1, and JUN. Results. Cumulatively, 790 active compounds and 1006 targets of HGWD were identified. A total of 4570 differentially expressed genes of RA with a p value <0.05 and log 2fold change > 0.5 were collected. Moreover, 739 GO entries of HGWD on RA were identified, and 79 pathways were screened based on GO and KEGG analysis. The core target gene of HGWD in RA treatment was JUN. Other key target genes included FOS, CCND1, IL6, E2F2, and ICAM1. It was confirmed that the TNF signaling pathway and IL-17 signaling pathway are important pathways of HGWD in the treatment of RA. The molecular docking results revealed that the top 10 active compounds of HGWD had a strong binding to the target proteins of VCAM1, CTNNB1, and JUN. Conclusion. HGWD has important active compounds such as quercetin, kaempferol, and beta-sitosterol, which exert its therapeutic effect on multiple targets and multiple pathways.

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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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Network pharmacology approach to reveals therapeutic mech-anism of traditional plants formulation used by Malaysia in-digenous ethnics in coronaviruses infection

10.26434/chemrxiv-2022-rpm1s ◽

2022 ◽

Author(s):

Fui Fui Lem ◽

Dexter Jiunn Herng Lee ◽

Fong Tyng Chee ◽

Su Na Chin ◽

Kai Min Lin ◽

...

Keyword(s):

Bioactive Compounds ◽

Target Genes ◽

Interaction Network ◽

Bioactive Compound ◽

Functional Enrichment ◽

Network Pharmacology ◽

Pathway Network ◽

Pharmacological Mechanism ◽

Target Network ◽

Compound Target

Network pharmacology analysis can act as a strategy to identify the pharmacological effect of plant-based bioactive compounds against coronavirus diseases. This study aimed to investigate the potential pharmacological mechanism of a local ethnomedicine (Costus speciosus, Hibiscus rosa-sinensis and Phyllanthus niruri) of Northern Borneo against coronaviruses known as CHP. Compounds in CHP were extracted from databases and screened for their oral bioavailability and drug-likeness before a compound-target network was built. Furthermore, the protein-protein interaction network and pathway enrichment were constructed and analyzed. A compound-target network consisting of 48 putative bioactive compounds targeting 587 candidate genes was identified. A total of 186 coronavirus-related genes were extracted and TP53, STAT3, HSP90AA1, STAT1, and EP300 were predicted to be the key targets. Notably, mapping of these target genes into the target-pathway network illustrated that functional enrichment was on viral infection and regulation of inflammation pathways. Urinatetralin is predicted, for the first time, as a bioactive compound that solely targets STAT3. The results from this study indicate that compounds present in CHP employ STAT3 and its connected pathways as the mechanism of action against coronaviruses. In conclusion, urinatetralin should be further investigated for its potential application against coronavirus infections.

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Anti-Inflammatory Mechanisms of Xuefu Zhuyu Decoction in The Treatment of Atherosclerosis Based on Network Pharmacology and Microarray Data Differences Analysis

10.21203/rs.3.rs-184004/v1 ◽

2021 ◽

Author(s):

Haoran Li ◽

Hongyun Wu ◽

Weiying Li ◽

Jie Yang ◽

Wei Peng

Keyword(s):

Molecular Docking ◽

Microarray Data ◽

Leukocyte Adhesion ◽

Enrichment Analysis ◽

Endothelial Cell Proliferation ◽

Network Pharmacology ◽

Biological Processes ◽

Effective Components ◽

Target Network ◽

Xuefu Zhuyu Decoction

Abstract Background: Xuefu Zhuyu decoction is a traditional Chinese formula composed of eleven herbs, which has the effect of promoting blood circulation and removing blood stasis. In this study, the anti-inflammatory mechanisms of Xuefu Zhuyu decoction in the treatment of atherosclerosis were studied utilizing network pharmacology, data mining, microarray data differences analysis and molecular docking.Methods: Analyzing data from the TCMSP, the effective components and key targets of Xuefu Zhuyu decoction were screened out. Atherosclerosis-related genes were extracted from the disease databases and determined according to differences analysis. The component-target network was constructed and gene enrichment analysis, as well as topology analysis, were carried out. Finally, the affinity between the target and the effective components was verified by molecular docking.Results: We screened 186 effective components of Xuefu Zhuyu decoction from TCMSP and obtained 126 targets. Through searching the disease databases and analyzing the results of differences analysis, two hundred and one atherosclerosis-related genes were obtained. After constructing the component-target network, it was found that Xuefu Zhuyu decoction played an anti-atherosclerotic role by acting on 21 targets. The results of enrichment analysis suggested that 21 key targets were mainly enriched in biological processes such as leukocyte adhesion and endothelial cell proliferation. The results of molecular docking showed that the key components of Xuefu Zhuyu decoction, have a good affinity with IL-6 and VEGFA.Conclusions: Our bioinformatics analyses suggest that Xuefu Zhuyu decoction plays an anti-atherosclerotic role by regulating biological processes such as leukocyte adhesion and endothelial cell proliferation. This study provides a theoretical basis for the further study of the indications of Xuefu Zhuyu decoction and the development of anti-atherosclerotic drugs.

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