Dataset Information

Antitumor Mechanisms of Curcumae Rhizoma Based on Network Pharmacology.

ABSTRACT: Curcumae Rhizoma, a traditional Chinese medication, is commonly used in both traditional treatment and modern clinical care. Its anticancer effects have attracted a great deal of attention, but the mechanisms of action remain obscure. In this study, we screened for the active compounds of Curcumae Rhizoma using a drug-likeness approach. Candidate protein targets with functions related to cancer were predicted by reverse docking and then checked by manual search of the PubMed database. Potential target genes were uploaded to the GeneMANIA server and DAVID 6.8 database for analysis. Finally, compound-target, target-pathway, and compound-target-pathway networks were constructed using Cytoscape 3.3. The results revealed that the anticancer activity of Curcumae Rhizoma potentially involves 13 active compounds, 33 potential targets, and 31 signaling pathways, thus constituting a "multiple compounds, multiple targets, and multiple pathways" network corresponding to the concept of systematic actions in TCM. These findings provide an overview of the anticancer action of Curcumae Rhizoma from a network perspective, as well as setting an example for future studies of other materials used in TCM.

SUBMITTER: Bi YH

PROVIDER: S-EPMC5832109 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antitumor Mechanisms of Curcumae Rhizoma Based on Network Pharmacology.

Bi Yan-Hua YH Zhang Li-Hua LH Chen Shao-Jun SJ Ling Qing-Zhi QZ

Evidence-based complementary and alternative medicine : eCAM 20180205

Curcumae Rhizoma, a traditional Chinese medication, is commonly used in both traditional treatment and modern clinical care. Its anticancer effects have attracted a great deal of attention, but the mechanisms of action remain obscure. In this study, we screened for the active compounds of Curcumae Rhizoma using a drug-likeness approach. Candidate protein targets with functions related to cancer were predicted by reverse docking and then checked by manual search of the PubMed database. Potential ...[more]

PMID: 29636777

Similar Datasets

Project description:Aim:To analyse the target of Rhizoma Curcumae in nasopharyngeal carcinoma by using network pharmacological techniques and to explore the associated molecular mechanism. Methods:The targets of nasopharyngeal carcinoma were retrieved from the GeneCards database. At the same time, the drug therapeutic targets of Rhizoma Curcumae were obtained from the TCMSP and SymMap databases. The data were imported into the STRING database and Cytoscape 3.7.1 to construct a network of "Chinese medicine component-target-disease" interactions; then, the intersection was screened as the core Rhizoma Curcumae antinasopharyngeal cancer targets. Through GO target function and KEGG pathway enrichment analyses of the core targets, we predicted the biological processes and key signalling pathways involved in the Rhizoma Curcumae treatment of nasopharyngeal carcinoma. Results:Twenty-five core targets of Rhizoma Curcumae in nasopharyngeal carcinoma were mined: TP53, BCL2 ICAM1 RXRA, TLR3 and TLR9, TNF, PTGS2, IL-6, CTSD, MMP2, MMP9, MMP14, TIMP2, ABCC1, ABCB1, ABCG2, and so on. The results of visual analysis showed that the Rhizoma Curcumae treatment of nasopharyngeal carcinoma mainly involves leukocyte adhesion to vascular endothelial cells, positive regulation of NF-?B import into the nucleus, regulation of the reactive oxygen species biosynthetic and metabolic process, regulation of the chemokine biosynthetic and metabolic process, various cancer-related signalling pathways, and a variety of cytokine signal transduction pathways, such as the NF-?B, TLR, IL-17, and TNF signalling pathways. Conclusion:The core targets predicted by our research can be used as molecular markers for the treatment and prediction of nasopharyngeal carcinoma. The mechanism of Rhizoma Curcumae treatment in NPC may be related to immune regulatory pathways, the inhibition of cancer cell proliferation, metastasis, and angiogenesis, as well as the regulation of tumour microenvironment. Combined with the prediction of its associated mechanism of action, the core targets can provide targeted reference value for subsequent drug development related to Curcuma.

Project description:BackgroundLung cancer has a poor prognosis and a high mortality rate, and patients may develop multidrug resistance. Sparganii Rhizoma-Curcumae Rhizoma (HCSC), the classic herbal drug combination of traditional Chinese medicine (TCM), is commonly used in treating tumors, but its molecular mechanism is still unclear.MethodWe explored the possible mechanisms underlying the antitumor effect of HCSC using network pharmacology. The bioactive components of HCSC and their targets were collected from the TCM Systems Pharmacology (TCMSP) database and PharmMapper. Gene Ontology (GO) and KEGG enrichment analyses were performed; the GeneMANIA platform was used for the functional enrichment analysis of the core targets and their neighboring genes. Molecular docking was performed between the bioactive components and core targets. HCSC freeze-dried powder was prepared, and the bioactive components were verified by liquid chromatography- (LC-) mass spectrometry (MS). Human lung adenocarcinoma H1975 cells were cultured to verify in vitro the molecular mechanism of action of HCSC in treating lung cancer, as predicted by network pharmacology. Finally, we used the Symmap database to predict the relationship between the herb and TCM syndrome.ResultA total of seven bioactive components were identified by network pharmacological analysis. Through enrichment analyses, it was found that the mechanism of action mainly involved mitochondrial-mediated caspase-dependent cell apoptosis signaling pathways. The results of molecular docking showed that the bioactive components in HCSC have a good affinity with the target proteins (ALB, BCL2L1, ESR1, HRAS, MAP2K1, MAPK14, and SIRT1). LC-MS confirmed that formononetin and bisdemethoxycurcumin were present in the HCSC freeze-dried powder, consistent with the prediction. The results of in vitro experiments on NCI-H1975 cells confirmed that HCSC can upregulate the mitochondrial-mediated caspase-dependent apoptosis signaling pathway by inducing the cleavage of caspase-3, caspase-9, and PARP, consistent with the network pharmacology prediction. Further, the qi deficiency and blood stasis associated with TCM syndrome can be treated with HCSC.

Project description:BackgroundAstragali Radix-Curcumae Rhizoma (ARCR), a classic drug pair, has been widely used for the treatment of gastric intraepithelial neoplasia (GIN) in China. However, the underlying mechanisms of this drug pair are still unknown. Thus, elucidating the molecular mechanism of ARCR for treating GIN is imperative.MethodsThe active components and targets of ARCR were determined from the TCMSP database, and the differentially expressed genes related to GIN were identified from the GSE130823 dataset. The protein-protein interaction (PPI) network and ARCR-active component-target-pathway network were constructed by STRING 11.0 and Cytoscape 3.7.2, respectively. In addition, a receiver operating characteristic curve (ROC) was conducted to verify the key targets, and enrichment analyses were performed using R software. Molecular docking was carried out to test the binding capacity between core active components and key targets.Results31 active components were obtained from ARCR, among which 22 were hit by the 51 targets associated with GIN. Gene Ontology (GO) functional enrichment analysis showed that biological process (BP), molecular function (MF), and cellular component (CC) were most significantly enriched in response to a drug, catecholamine binding, and apical part of the cell, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated ARCR against GIN through regulation of neuroactive ligand-receptor interaction, nitrogen metabolism, calcium signaling pathway, chemical carcinogenesis-receptor activation, drug metabolism, gap junction, and cancers. In the PPI network, 15 potential targets were identified, of which nine key targets were proven to have higher diagnostic values in ROC. Molecular docking revealed a good binding affinity of active components (quercetin, bisdemethoxycurcumin, and kaempferol) with the corresponding targets (CYP3A4, CYP1A1, HMOX1, DRD2, DPP4, ADRA2A, ADRA2C, NR1I2, and LGALS4).ConclusionThis study revealed the active components and molecular mechanism by which ARCR treatment is effective against GIN through regulating multipathway, such as neuroactive ligand-receptor interaction, nitrogen metabolism, and calcium signaling pathway.

Project description:BackgroundAlzheimer's disease (AD) is becoming a more prevalent public health issue in today's culture. The experimental study of Coptidis Rhizoma (CR) and its chemical components in AD treatment has been widely reported, but the principle of multi-level and multi-mechanism treatment of AD urgently needs to be clarified.ObjectiveThis study focuses on network pharmacology to clarify the mechanism of CR's multi-target impact on Alzheimer's disease.MethodsThe Phytochemical-compounds of CR have been accessed from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and Symmap database or HPLC determination. The values of Oral Bioavailability (OB) ≥ 30% and Drug Like (DL) ≥ 0.18 or blood ingredient were used to screen the active components of CR; the interactive network of targets and compounds were constructed by STRING and Cytoscape platform, and the network was analyzed by Molecular Complex Detection (MCODE); Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) and metabolic pathway enrichment of targets were carried out with Metascape, the Database for Annotation, Visualization and Integrated Discovery (DAVID) and MetaboAnalyst platform; Based on CytoHubba, the potential efficient targets were screened by Maximal Clique Centrality (MCC) and Degree, the correlation between potential efficient targets and amyloid β-protein (Aβ), Tau pathology was analyzed by Alzdata database, and the genes related to aging were analyzed by Aging Altas database, and finally, the core targets were obtained; the binding ability between ingredients and core targets evaluated by molecular docking, and the clinical significance of core targets was assessed with Gene Expression Omnibus (GEO) database.Results19 active components correspond to 267 therapeutic targets for AD, of which 69 is potentially effective; in module analysis, RELA, TRAF2, STAT3, and so on are the critical targets of each module; among the six core targets, RELA, MAPK8, STAT3, and TGFB1 have clinical therapeutic significance; GO function, including 3050 biological processes (BP), 257 molecular functions (MF), 184 cellular components (CC), whose functions are mainly related to antioxidation, regulation of apoptosis and cell composition; the HIF-1 signaling pathway, glutathione metabolism is the most significant result of 134 KEGG signal pathways and four metabolic pathways, respectively; most of the active components have an excellent affinity in docking with critical targets.ConclusionThe pharmacological target prediction of CR based on molecular network pharmacology paves the way for a multi-level networking strategy. The study of CR in AD treatment shows a bright prospect for curing neurodegenerative diseases.

Dataset Information

Antitumor Mechanisms of Curcumae Rhizoma Based on Network Pharmacology.

Publications

Antitumor Mechanisms of Curcumae Rhizoma Based on Network Pharmacology.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets