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

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.

scholarly journals Network Pharmacology-Based Investigation into the Mechanisms of Quyushengxin Formula for the Treatment of Ulcerative Colitis

2019 ◽  
Vol 2019 ◽  
pp. 1-22
Author(s):  
Haojie Yang ◽  
Ying Li ◽  
Sichen Shen ◽  
Dan Gan ◽  
Changpeng Han ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Bioactive Compounds ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Disease Network ◽  
Pathway Network ◽  
Similarity Algorithm ◽  
Target Network ◽  
Target Disease ◽  
Compound Target

Objective. Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease whose treatment strategies remain unsatisfactory. This study aims to investigate the mechanisms of Quyushengxin formula acting on UC based on network pharmacology. Methods. Ingredients of the main herbs in Quyushengxin formula were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Absorption, distribution, metabolism, and excretion properties of all ingredients were evaluated for screening out candidate bioactive compounds in Quyushengxin formula. Weighted ensemble similarity algorithm was applied for predicting direct targets of bioactive ingredients. Functional enrichment analyses were performed for the targets. In addition, compound-target network, target-disease network, and target-pathway network were established via Cytoscape 3.6.0 software. Results. A total of 41 bioactive compounds in Quyushengxin formula were selected out from the TCMSP database. These bioactive compounds were predicted to target 94 potential proteins by weighted ensemble similarity algorithm. Functional analysis suggested these targets were closely related with inflammatory- and immune-related biological progresses. Furthermore, the results of compound-target network, target-disease network, and target-pathway network indicated that the therapeutic effects of Quyushengxin on UC may be achieved through the synergistic and additive effects. Conclusion. Quyushengxin may act on immune and inflammation-related targets to suppress UC progression in a synergistic and additive manner.

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

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.

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

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
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.

Virtual Screening of Potential Anti-fatigue Mechanism of Polygonati Rhizoma Based on Network Pharmacology

2020 ◽  
Vol 22 (9) ◽  
pp. 612-624 ◽  
Author(s):  
Ze-Feng Wang ◽  
Ye-Qing Hu ◽  
Qi-Guo Wu ◽  
Rui Zhang
Keyword(s):  
Virtual Screening ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Vital Role ◽  
Network Pharmacology ◽  
Pathway Network ◽  
Protein Protein Interaction ◽  
Target Network ◽  
Protein Protein Interaction Network ◽  
Fatigue Mechanism

Background and Objective: A large number of people are facing the danger of fatigue due to the fast-paced lifestyle. Fatigue is common in some diseases, such as cancer. The mechanism of fatigue is not definite. Traditional Chinese medicine is often used for fatigue, but the potential mechanism of Polygonati Rhizoma (PR) is still not clear. This study attempts to explore the potential anti-fatigue mechanism of Polygonati Rhizoma through virtual screening based on network pharmacology. Methods: The candidate compounds of PR and the known targets of fatigue are obtained from multiple professional databases. PharmMapper Server is designed to identify potential targets for the candidate compounds. We developed a Herbal medicine-Compound-Disease-Target network and analyzed the interactions. Protein-protein interaction network is developed through the Cytoscape software and analyzed by topological methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment are carried out by DAVID Database. Finally, we develop Compound-Target-Pathway network to illustrate the anti-fatigue mechanism of PR. Results: This approach identified 12 active compounds and 156 candidate targets of PR. The top 10 annotation terms for GO and KEGG were obtained by enrichment analysis with 35 key targets. The interaction between E2F1 and PI3K-AKT plays a vital role in the anti-fatigue effect of PR due to this study. Conclusions: This study demonstrates that PR has multi-component, multi-target and multipathway effects.

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

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.

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

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.

scholarly journals Mechanisms of Core Chinese Herbs against Colorectal Cancer: A Study Based on Data Mining and Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Tong Lin ◽  
Caijun Liang ◽  
Wenya Peng ◽  
Yuqin Qiu ◽  
Lisheng Peng
Keyword(s):  
Colorectal Cancer ◽  
Data Mining ◽  
Bioactive Compounds ◽  
Target Genes ◽  
Prognostic Significance ◽  
Therapeutic Targets ◽  
Docking Simulation ◽  
Functional Enrichment ◽  
Chinese Herbs ◽  
Network Pharmacology

Colorectal cancer (CRC) is now the second most deadly cancer globally. Chinese herbal medicine (CHM) plays an indispensable role in CRC treatment in China. However, the core herbs (the CHs) in the treatment of CRC and their underlying therapeutic mechanisms remain unclear. This study aims to uncovering the CHs and their mechanisms of action of CRC treatment, applying data mining and network pharmacology approach. First, CHM prescriptions treating CRC were collected from clinical studies from the Chinese National Knowledge Infrastructure (CNKI) and MEDLINE databases, and the CHs were identified through data mining. Then, the bioactive compounds and the corresponding putative targets of the CHs were obtained from three traditional Chinese medicine (TCM) databases. CRC related targets were acquired from three disease databases; the overlapping targets between the CHs and CRC were identified as the therapeutic targets. Subsequently, functional enrichment analysis was performed to elucidate the mechanisms of the CHs on CRC. Moreover, networks were constructed to screen the major bioactive compounds and therapeutic targets. Finally, prognostic values of the major target genes were evaluated by survival analysis, and molecular docking simulation was performed to assess the binding affinity of key targets and major bioactive compounds. It came out that 10 the CHs from 113 prescriptions and 190 bioactive compounds with 118 therapeutic targets were identified. The therapeutic targets were mainly enriched in the biological progress of transcription, apoptosis, and response to cytokine. Various cancer-associated signaling pathways, including microRNAs, TNF, apoptosis, PI3K-Akt, and p53, were involved. Furthermore, 15 major bioactive compounds and five key target genes (VEGFA, CASP3, MYC, CYP1Y1, and NFKB1) with prognostic significance were identified. Additionally, most major bioactive compounds might bind firmly to the key target proteins. This study provided an overview of the anti-CRC mechanisms of the CHs, which might refer to the regulation of apoptosis, transcription, and inflammation.

scholarly journals Cell Cycle Arrest, An Important Mechanism of Action of Compound Kushen Injection, Prevents Colorectal Cancer: Network Pharmacology Analysis and Experimental Validation

2021 ◽  
Author(s):  
Jie Sun ◽  
Mei Li ◽  
Di Wang ◽  
Tingru Lin ◽  
Jingyi Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Experimental Validation ◽  
Bioactive Compound ◽  
Network Pharmacology ◽  
Pathway Network ◽  
Cycle Arrest ◽  
Compound Kushen Injection ◽  
Compound Target

Abstract Compound Kushen injection (CKI) is the most widely used traditional Chinese medicine preparation for the comprehensive treatment of colorectal cancer (CRC) in China, but its underlying molecular mechanisms of action are still unclear. The present study employed a network pharmacology approach, in which we constructed a “bioactive compound-target-pathway” network. Experimental RNA sequencing (RNA-Seq) analysis was performed to identify a key “bioactive compound-target-pathway” network for subsequent experimental validation. Cell cycle, proliferation, autophagy, and apoptosis assays and a model of azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis in mice were employed to detect the biological effect of CKI on CRC. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were performed to verify the selected targets and pathways. We constructed a predicted network that included 82 bioactive compounds, 34 targets, and 33 pathways and further screened an anti-CRC CKI “biological compound (hesperetin 7-O-rutinoside, genistein 7-O-rutinoside, and trifolirhizin)-target (p53 and checkpoint kinase 1 [CHEK1])” network that targeted the “cell cycle pathway”. Validation experiments showed that CKI effectively induced the cell-cycle arrest of CRC cells in vitro and suppressed the development of CRC in vivo by downregulating the expression of p53 and CHEK1. Our findings confirmed that inducing cell-cycle arrest by CKI is an important mechanism of its anti-CRC action, which provides a direct and scientific experimental basis for the clinical application of CKI.

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

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.

scholarly journals Network-based analysis on the pharmacological mechanisms underlying the anti-diabetic property of Coix lachryma-jobi

2021 ◽  
Author(s):  
Arvin A Tanquiqui ◽  
Angelu Mae A Ferrer ◽  
Janella Rayne A David ◽  
Custer C Deocaris ◽  
Malona Velasco Alinsug
Keyword(s):  
Diabetes Mellitus ◽  
Bioactive Compounds ◽  
Target Genes ◽  
Interaction Network ◽  
Bioactive Compound ◽  
Regulation Of Transcription ◽  
Protein Protein Interaction ◽  
Treatment Of Diabetes ◽  
Go Terms ◽  
Protein Protein Interaction Network

Diabetes mellitus (DM) is the most common endocrine disorder and among the top 10 leading diseases causing death worldwide. Coicis semen [CS] (Coix lachryma-jobi L.), also known as adlay have been reported to display anti-diabetic properties. Unfortunately, studies on the pharmacological mechanisms involving adlay for the treatment of diabetes are nil. Thus, this study was conducted to evaluate the interactions and mechanisms of the bioactive compound targets of adlay in the treatment of diabetes using network analysis. Adlay bioactive compounds and potential target genes were obtained from SymMap. Diabetes related target genes were collected from CTD. Protein-Protein Interaction Network was analyzed using the STRING database. GO and KEGG pathway enrichment analyses were performed using DAVID to further explore the mechanisms of adlay in treating diabetes. PPI and compound-target-pathway were visualized using Cytoscape. A total of 25 bioactive compounds, 201 corresponding targets, and 35839 diabetes mellitus associated targets were obtained while 200 were considered potential therapeutic targets. The 9 bioactive compounds studied were berberine, oleic acid, beta-sitosterol, sitosterol, linoleic acid, berberrubine, jatrorrhizine, thalifendine, and stigmasterol. The identified 5 core targets were ESR1, JUN, MAPK14, and RXRA. Adlai targets enriched in GO terms were mostly involved with positive regulation of transcription, response to drugs, and negative regulation of apoptosis. This study provides novel research insights into the clinical properties of adlay in diabetes melitus treatment.

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