Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

Abstract Background: Colon cancer is increasing recently but the high cost and adverse side effects experienced always leads to treatment drop out. Zingiber officinale, commonly known as ginger, is a popular herbal medicine and this study was aimed to identify the active compounds from ginger and to investigate its anti-cancer mechanisms through network pharmacology construction. Results: Ginger compounds were discerned through the TCMSP, which were filtered by the metrics of oral bioavailability and drug likeness, and its related targets were searched. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. Six potential active compounds, 288 interacting targets in addition to 1356 disease-related targets were collected, of which 114 intersection targets were obtained. The PPI network showed that 32 targets including SRC, PIK3R1, and TP53 were identified as key targets. These targets were mainly associated with the biological processes like transmembrane receptor protein tyrosine kinase signaling pathway, regulation of cellular protein localization, cellular response to oxidative stress. KEGG enrichment manifested that ginger probably produced preventive effects against colon cancer by regulating significant signaling pathway like pathway in cancer, hepatitis B, and estrogen signaling pathway. TP53, HSP90AA1, MAPK8, JAK2, CASP3, and ERBB2 could be viewed as the most potential target proteins, which were validated by molecular docking simulation.Conclusion: This study demonstrated the multi-component, multi-target, and multi-pathway characteristics of ginger, providing novel insight for ginger compounds developed as new drug for anti-colon cancer.

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Systematic Understanding of Mechanism of Danggui Shaoyao San against Ischemic Stroke Using a Network Pharmacology Approach

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2022/3747285 ◽

2022 ◽

Vol 2022 ◽

pp. 1-20

Author(s):

Sijie Li ◽

Yong Yang ◽

Wei Zhang ◽

Haiyan Li ◽

Wantong Yu ◽

...

Keyword(s):

Ischemic Stroke ◽

Molecular Docking ◽

Western Blot ◽

Signaling Pathway ◽

Cellular Response ◽

Network Pharmacology ◽

Active Compounds ◽

The Core ◽

Target Network ◽

Compound Target

Purpose. Danggui Shaoyao San (DSS) was developed to treat the ischemic stroke (IS) in patients and animal models. The purpose of this study was to explore its active compounds and demonstrate its mechanism against IS through network pharmacology, molecular docking, and animal experiment. Methods. All the components of DSS were retrieved from the pharmacology database of TCM system. The genes corresponding to the targets were retrieved using OMIM, CTD database, and TTD database. The herb-compound-target network was constructed by Cytoscape software. The target protein-protein interaction network was built using the STRING database. The core targets of DSS were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, we achieved molecular docking between the hub proteins and the key active compounds. Finally, animal experiments were performed to verify the core targets. Triphenyltetrazolium chloride (TTC) staining was used to calculate the infarct size in mice. The protein expression was determined using the Western blot. Results. Compound-target network mainly contained 51 compounds and 315 corresponding targets. Key targets contained MAPK1, SRC, PIK3R1, HRAS, AKT1, RHOA, RAC1, HSP90AA1, and RXRA FN1. There were 417 GO items in GO enrichment analysis ( p < 0.05 ) and 119 signaling pathways ( p < 0.05 ) in KEGG, mainly including negative regulation of apoptosis, steroid hormone-mediated signaling pathway, neutrophil activation, cellular response to oxidative stress, and VEGF signaling pathway. MAPK1, SRC, and PIK3R1 docked with small molecule compounds. According to the Western blot, the expression of p-MAPK 1, p-AKT, and p-SRC was regulated by DSS. Conclusions. This study showed that DSS can treat IS through multiple targets and routes and provided new insights to explore the mechanisms of DSS against IS.

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Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

10.21203/rs.3.rs-38111/v2 ◽

2020 ◽

Author(s):

MengMeng Zhang ◽

Dan Wang ◽

Feng Lu ◽

Rong Zhao ◽

Xun Ye ◽

...

Keyword(s):

Colon Cancer ◽

Molecular Docking ◽

Cancer Prevention ◽

Signaling Pathways ◽

Cellular Response ◽

Endocrine Resistance ◽

Docking Simulation ◽

Network Pharmacology ◽

Integrated Network ◽

Colon Cancer Prevention

Abstract Background and objective: Colon cancer is increasing in people recently and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent against colon cancer. This study was aimed to identify the bioactive compounds and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach.Methods: Putative ingredients of ginger and its related targets were discerned from the TCMSP database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape.Results: Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, including cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, MAPK8, JAK2, CASP3, and ERBB2 were viewed as the most important genes, which were validated by molecular docking simulation.Conclusion: This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-target and multi-pathway with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.

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Study on the Mechanism of Acori Graminei Rhizoma in the Treatment of Alzheimer’s Disease Based on Network Pharmacology and Molecular Docking

BioMed Research International ◽

10.1155/2021/5418142 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yi Kuan Du ◽

Yue Xiao ◽

Shao Min Zhong ◽

Yi Xing Huang ◽

Qian Wen Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Signaling Pathway ◽

Target Prediction ◽

Enrichment Analysis ◽

The Elderly ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Active Components

Alzheimer’s disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer’s disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of “drug-active ingredient-ingredient target.” A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer’s disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer’s signal pathway, thus reducing the production of Aβ, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.

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Integrating Data Mining, Network Pharmacology, and Molecular Docking Verification to Investigate the Molecular Mechanism of Traditional Chinese Medicine Prescriptions for Treating Male Infertility

10.21203/rs.3.rs-264555/v1 ◽

2021 ◽

Author(s):

Xue Bai ◽

Yibo Tang ◽

Qiang Li ◽

Guimin Liu ◽

Dan Liu ◽

...

Keyword(s):

Data Mining ◽

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Male Infertility ◽

Signaling Pathway ◽

Molecular Mechanism ◽

Oxidant Stress ◽

Estrogen Signaling ◽

Network Pharmacology

Abstract Background: Male infertility (MI) affects almost 5% adult men worldwide, and 75% of these cases are unexplained idiopathic. There are limitations in the current treatment due to the unclear mechanism of MI, which highlight the urgent need for a more effective strategy or drug. Traditional Chinese Medicine (TCM) prescriptions have been used to treat MI for thousands of years, but their molecular mechanism is not well defined. Methods: Aiming at revealing the molecular mechanism of TCM prescriptions on MI, a comprehensive strategy integrating data mining, network pharmacology, and molecular docking verification was performed. Firstly, we collected 289 TCM prescriptions for treating MI from National Institute of TCM Constitution and Preventive Medicine for 6 years. Then, Core Chinese Materia Medica (CCMM), the crucial combination of TCM prescriptions, was obtained by the TCM Inheritance Support System from China Academy of Chinese Medical Sciences. Next, the components and targets of CCMM in TCM prescriptions and MI-related targets were collected and analyzed through network pharmacology approach.Results: The results showed that the molecular mechanism of TCM prescriptions for treating MI are regulating hormone, inhibiting apoptosis, oxidant stress and inflammatory. Estrogen signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway are the most important signaling pathways. Molecular docking experiments were used to further validate network pharmacology results. Conclusions: This study not only discovers CCMM and the molecular mechanism of TCM prescriptions for treating MI, but may be helpful for the popularization and application of TCM treatment.

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Exploration of the mechanism of Ziyin Tongluo Formula on preventing and treating postmenopausal osteoporosis based on the network pharmacology and molecular docking

10.21203/rs.3.rs-39351/v2 ◽

2020 ◽

Author(s):

Rong-Bin Chen ◽

Ying-Dong Yang ◽

Kai Sun ◽

Shan Liu ◽

Wei Guo ◽

...

Keyword(s):

Molecular Docking ◽

Postmenopausal Osteoporosis ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Active Ingredients ◽

Active Compounds ◽

Core Proteins ◽

Key Genes

Abstract Background: Postmenopausal osteoporosis (PMOP) is a global chronic and metabolic bone disease, which poses huge challenges to individuals and society. Ziyin Tongluo Formula (ZYTLF) has been proved effective in the treatment of PMOP. However, the material basis and mechanism of ZYLTF against PMOP have not been thoroughly elucidated.Methods: Online databases were used to identify the active ingredients of ZYTLF and corresponding putative targets. Genes associated with PMOP were mined, and then mapped with the putative targets to obtain overlapping genes. Multiple networks were constructed and analyzed, from which the key genes were selected. The key genes were imported to the DAVID database to performs GO and KEGG pathway enrichment analysis. Finally, AutoDock Tools and other software were used for molecular docking of core compounds and key proteins. Results: Ninety-two active compounds of ZYTLF corresponded to 243 targets, with 129 target genes interacting with PMOP, and 50 key genes were selected. Network analysis showed the top 5 active ingredients including quercetin, kaempferol, luteolin, scutellarein, and formononetin., and the top 50 key genes such as VEGFA, MAPK8, AKT1, TNF, ESR1. Enrichment analysis uncovered two significant types of KEGG pathways in PMOP, hormone-related signaling pathways (estrogen , prolactin, and thyroid hormone signaling pathway) and inflammation-related pathways (TNF, PI3K-Akt, and MAPK signaling pathway). Moreover, molecular docking analysis verified that the main active compounds were tightly bound to the core proteins, further confirming the anti-PMOP effects. Conclusions: Based on network pharmacology and molecular docking technology, this study initially revealed the mechanisms of ZYTLF on PMOP, which involves multiple targets and multiple pathways.

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Exploring the Mechanisms Underlying the Therapeutic Effect of Xixin Decoction on Alzheimer's Disease Based on Network Pharmacology and Molecular Docking

10.21203/rs.3.rs-562321/v1 ◽

2021 ◽

Author(s):

Zhuo Zhang ◽

Jiang-lin Xu ◽

Ming-qing Wei ◽

Ting Li ◽

Jing Shi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Signaling Pathway ◽

Therapeutic Effect ◽

Mapk Signaling ◽

Network Pharmacology ◽

Receptor Interaction ◽

Ppi Network ◽

Active Compounds

Abstract Background and objective: Alzheimer’s disease (AD) has been a worldwide problem, not only the treatment but also the prevention. As a commonly used Chinese Herbal Formula, Xixin Decoction (XXD) has significant therapeutic effect on AD but without clear mechanism. This study was aimed to predict the main active compounds and targets of XXD in the treatment of AD and to explore the potential mechanism by using network pharmacology and molecular docking. Methods: The compounds of XXD were searched in the TCMSP and the TCMID database, and the active compounds were screened based on the ADME model and SwissADME platform. SwissTargetPrediction platform was used to search for the primary candidate targets of XXD. The common targets related to AD obtained by two databases (GeneCards and DisGeNET) were determined as candidate proteins involved in AD. To acquire the related targets of XXD in the treatment of AD, the target proteins related to AD were intersected with the predicted targets of XXD. Then these overlapping targets were imported into the STRING database to build PPI network including hub targets; Cytoscape 3.7.2 software was used to construct the topology analysis for the herb-compound-target network diagram while one of it’s plug-in called CytoNCA was used to calculate degree value to screen the main active compounds of XXD. GO and KEGG pathway enrichment analyses were conducted to explore the core mechanism of action and biological pathways associated with the decoction via Metascape platform. We used AutoDock Vina and PyMOL 2.4.0 softwares for molecular docking of hub targets and main compounds.Results: We determined 114 active compounds which meet the conditions of ADME screening, 973 drug targets, and 973 disease targets. However, intersection analysis screened out 208 shared targets. PPI network identified 9 hub targets, including TP53, PIK3CA, MAPK1, MAPK3, STAT3, AKT1, etc. The 10 main active compounds play a major role in treatment of AD by XXD. Hub targets were found to be enriched in 10 KEGG pathways, involving the Pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, Alzheimer's disease, Neuroactive ligand-receptor interaction, Dopaminergic synapse, Serotonergic synapse and MAPK signaling pathway. The docking results indicated that the 8 hub targets exhibit good binding activity with the 9 main active compounds of XXD.Conclusions: We found the advantages of multi-compounds-multi-targets-multi-pathways regulation to reveal the mechanism of XXD for treating AD based on network pharmacology and molecular docking. Our study provided a theorical basis for further clinical application and experimental research of XXD for anti-AD in the future.

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Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma

10.21203/rs.3.rs-60894/v3 ◽

2021 ◽

Author(s):

Zhiqiang Chen ◽

Tong Lin ◽

Xiaozhong Liao ◽

Zeyun Li ◽

Ruiting Lin ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathways ◽

Signaling Pathway ◽

Experimental Results ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Components ◽

Active Compounds ◽

Apoptosis Rate

Abstract Background: Cholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods: By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results: 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusion:As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

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Study on the Multitarget Mechanism of Sanmiao Pill on Gouty Arthritis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9873739 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Huiqin Qian ◽

Qianqian Jin ◽

Yichen Liu ◽

Ning Wang ◽

Yuru Chu ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Gouty Arthritis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Regulation Of Transcription ◽

Receptor Signaling ◽

Active Compounds ◽

Receptor Signaling Pathway ◽

Compound Target

Sanmiao pill (SMP), a Chinese traditional formula, had been used to treat gouty arthritis (GA). However, the active compounds and underlying mechanism remained unclear. Hence, network pharmacology and molecular docking were utilized to explore bioactive compounds and potential mechanism of action of SMP in treating GA. In the study, the compounds of SMP, corresponding targets, and GA-related targets were mined from various pharmacological databases. Then, herb-compound-target, compound-target, PPI, and target-pathway networks were constructed. Ultimately, molecular docking was carried out to verify the predicted results. The results indicated that 47 active compounds, 338 targets, and 144 disease targets were collected. Network analysis implied that Phellodendron chinense Schneid. played a vital role in the whole formula. Moreover, 7 compounds (quercetin, kaempferol, wogonin, rutaecarpine, baicalein, beta-sitosterol, and stigmasterol) and 4 targets (NFKB1, RELA, MAPK1, and TNF) might be the kernel compounds and targets of SMP against GA. According to GOBP and KEGG pathway enrichment analysis and target-pathway network, SMP might exert a therapeutic role in GA by regulating numerous biological processes and pathways, including lipopolysaccharide-mediated signaling pathway, positive regulation of transcription, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, NOD-like receptor signaling pathway, and MAPK signaling pathway. The results of molecular docking showcased that 11 pairs of compound with targets had tight binding strength. Thereinto, 4 compounds of MAPK1 and 5 compounds of NFKB1 possessed a better combination, suggesting that MAPK1 and NFKB1 might be considered as therapeutic targets in treatment of GA. This study verified that SMP had synergistic effect on GA by multicomponents, multitargets, and multipathways.

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Integrating Network Pharmacology and Experimental Validation Deciphers the Mechanism of Guizhi Fuling Wan against Adenomyosis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6034147 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Haoxian Wang ◽

Jihong Zhang ◽

Qinqin Zhu ◽

Xianyun Fu ◽

Chenjie Li

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Kegg Pathway ◽

Animal Experiments ◽

Enrichment Analysis ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Pathway Enrichment ◽

Verification Methods

Aim. This study aimed to predict the key targets and endocrine mechanisms of Guizhi Fuling Wan (GZFLW) in treating adenomyosis (AM) through network pharmacology, molecular docking, and animal experiment verification. Methods. The related ingredients and targets of GZFLW in treating AM were screened out using TCMSP, BATMAN-TCM, SwissTargetPrediction, and PubChem Database. Then, the protein-protein interaction (PPI) analysis and the network of compound-hub targets were constructed. At the same time, the key targets were uploaded to the Metascape Database for KEGG pathway enrichment analysis. After that, the molecular docking technology of the main active components and hub targets was performed. Furthermore, animal experiments were used to verify the results of network pharmacology analysis. Results. A total of 55 active ingredients of GZFLW and 44 overlapping targets of GZFLW in treating AM were obtained. After screening, 25 hub targets were collected, including ESR1, EGF, and EGFR. Then, the KEGG pathway enrichment analysis results indicated that the endocrine therapeutic mechanism of GZFLW against AM is mainly associated with the estrogen signaling pathway, endocrine resistance, and an EGFR tyrosine kinase signaling pathway. Then, molecular docking showed that the significant compounds of GZFLW had a strong binding ability with ERα and EGFR. More importantly, the animal experiments confirmed that the GZFLW could downregulate the abnormal infiltration of the endometrial epithelium into the myometrium and had no interference with the normal sexual cycle. This effect may be directly related to intervening the local estrogen signaling pathway of the endometrial myometrial interface (EMI). It may also be associated with the myometrium cells’ estrogen resistance via GPER/EGFR signaling pathway. Conclusion. The endocrine mechanism of GZFLW in treating AM was explored based on network pharmacology, molecular docking, and animal experiments, which provided a theoretical basis for the clinical application of GZFLW.

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Exploring the Antiglioma Mechanisms of Luteolin Based on Network Pharmacology and Experimental Verification

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/7765658 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Renxuan Huang ◽

Rui Dong ◽

Nan Wang ◽

Beiwu Lan ◽

Hongyang Zhao ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Fruits And Vegetables ◽

Docking Simulation ◽

Underlying Mechanism ◽

Venn Diagram ◽

Network Pharmacology ◽

Discovery Studio ◽

Inorganic Substances

Luteolin, a natural flavone compound, exists in a variety of fruits and vegetables, and its anticancer effect has been shown in many studies. However, its use in glioma treatment is hampered due to the fact that the underlying mechanism of action has not been fully explored. Therefore, we elucidated the potential antiglioma targets and pathways of luteolin systematically with the help of network pharmacology and molecular docking technology. The druggability of luteolin, including absorption, excretion, distribution, and metabolism, was assessed via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The potential targets of luteolin and glioma were extracted from public databases, and the intersecting targets between luteolin and glioma were integrated and visualized by a Venn diagram. In addition, GO and KEGG pathway analysis was engaged in Metascape. The network of the luteolin-target-pathway was visualized by Cytoscape. Ultimately, the interactions between luteolin and predicted key targets were confirmed by Discovery studio software. According to the ADME results, luteolin shows great potential for development into a drug. 4860 glioma-associated targets and 280 targets of luteolin were identified, of which 205 were intersection targets. 6 core targets of luteolin against glioma, including AKT1, JUN, ALB, MAPK3, MAPK1, and TNF, were identified via PPI network analysis of which AKT1, JUN, ALB, MAPK1, and TNF harbor diagnostic value. The biological processes of luteolin are mainly involved in the response to inorganic substances, response to oxidative stress, and apoptotic signaling pathway. The essential pathways of luteolin against glioma involve pathways in cancer, the PI3K-Akt signaling pathway, the TNF signaling pathway, and more. Meanwhile, luteolin’s interaction with six core targets was verified by molecular docking simulation and its antiglioma effect was verified by in vitro experiments. This study suggests that luteolin has a promising potential for development into a drug and, moreover, it displays preventive effects against glioma by targeting various genes and pathways.

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