scholarly journals Effect and mechanism of Acoritataninowii Rhizoma and Curcumae Radix on chronic gastritis: a network pharmacology study

2020 ◽  
Author(s):  
Ling Zhang ◽  
Yunkai Dai ◽  
Yuping Li ◽  
Weijing Chen ◽  
Ruliu Li ◽  
...  

Abstract Background Chronic gastritis (CG) is an inflammatory disease which is one of the common diseases of the digestive system. To investigate the mechanisms of herbal pair Acoritataninowii Rhizoma(Shichangpu, AR) and Curcumae Radix༈Yujin, CR༉ in treatment of CG based on the network pharmacology. Methods The possible active ingredients and targets of AR-CR were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The UniProt database was used to query the human gene corresponding to each target protein. The genes related to CG were collected from the GeneCards database, the OMIM database, the DisGeNET database and the PharmGKB database. Intersected the target genes of AR-CR and CG, then protein-protein interaction(PPI) network was constructed by STRING website. The overlapped genes were subjected to gene ontology༈GO༉enrichment and Kyoto encyclopedia of genes and genomes༈KEGG༉pathway enrichment analyses by David. Results 45 intersection genes were obtained, and there were 40 targets in the PPI network for protein interaction, the kernel targets with Degree ≥ 10 included AKT1, TNF, JUN, MAPK3, MAPK8 and MAPK1. The Go enrichment analysis was mainly related to protein binding, enzyme binding, protein homodimerization activity, etc. The KEGG pathway enrichment analyses mainly involved the Pathways in cancer, TNF signaling pathway, Apoptosis, and VEGF signaling pathway. Conclusion AR-CR might delayed, blocked or reversed the atrophy, intestinal metaplasia, dysplasia and canceration of gastric mucosa by targeting key proteins and signal pathways,achieved the effect of the treatment of CG.

2021 ◽  
Vol 29 ◽  
pp. 239-256
Author(s):  
Qian Wang ◽  
Lijing Du ◽  
Jiana Hong ◽  
Zhenlin Chen ◽  
Huijian Liu ◽  
...  

BACKGROUND: Shanmei Capsule is a famous preparation in China. However, the related mechanism of Shanmei Capsule against hyperlipidemia has yet to be revealed. OBJECTIVE: To elucidate underlying mechanism of Shanmei Capsule against hyperlipidemia through network pharmacology approach and molecular docking. METHODS: Active ingredients, targets of Shanmei Capsule as well as targets for hyperlipidemia were screened based on database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed via Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 database. Ingredient-target-disease-pathway network was visualized utilizing Cytoscape software and molecular docking was performed by Autodock Vina. RESULTS: Seventeen active ingredients in Shanmei Capsule were screened out with a closely connection with 34 hyperlipidemia-related targets. GO analysis revealed 40 biological processes, 5 cellular components and 29 molecular functions. A total of 15 signal pathways were enriched by KEGG pathway enrichment analysis. The docking results indicated that the binding activities of key ingredients for PPAR-α are equivalent to that of the positive drug lifibrate. CONCLUSIONS: The possible molecular mechanism mainly involved PPAR signaling pathway, Bile secretion and TNF signaling pathway via acting on MAPK8, PPARγ, MMP9, PPARα, FABP4 and NOS2 targets.


2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.


2021 ◽  
Author(s):  
Xiaojian Wang ◽  
Rui Wang ◽  
Ting Xu ◽  
Hongting Jin ◽  
Peijian Tong ◽  
...  

Abstract Background The lesion of marrow is a crucial factor in orthopedic diseases, which is recognized by orthopedics-traumatology expert from "Zhe-School of Chinese Medicine". The Chinese herbs of regulating marrow has been widely used to treat osteonecrosis of the femoral head (ONFH) in China, while the interaction mechanisms were still elucidated. Thus, we conducted this study to explore the underlying mechanism of the five highest-frequency Chinese herbs of regulating marrow(HF-CHRM) in the treatment of ONFH with the aid of network pharmacology(NP) and molecular docking(MD). Methods The active components and potential targets of HF-CHRM were obtained through several online databases, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), UniProt database. The gene targets related to ONFH were collected with the help of the OMIM and GeneCards disease-related databases. The "drug- component-target-disease" network and protein-protein interaction(PPI) network of the drug and disease intersecting targets were constructed by using Cytoscape software and the STRING database. R software was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The MD of critical components and targets was carried out using Autodock Vina and Pymol to validate the binding affinity. Results A total of 54 active components, 1074 drug targets and 195 gene targets were obtained. There were 1219 ONFH related targets. 39 drug and disease intersection targets(representative genes: IL6, TP53, VEGFA, ESR1, IL1B) were obtained and considered potential therapeutic targets. 1619 items were obtained by the GO enrichment analysis, including 1517 biological processes, 10 cellular components and 92 molecular functions, which is mainly related to angiogenesis, bone and lipid metabolism and inflammatory reaction. The KEGG pathway enrichment analysis revealed 119 pathways, including AGE-RAGE signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway. MD results showed that quercetin, wogonin, and kaempferol active components had good affinity with IL6, TP53, and VEGFA core proteins. Conclusion The HF-CHRM can treat ONFH by multi-component, multi-target, and multi-pathway comprehensive action.


2020 ◽  
Author(s):  
wenxing su ◽  
biao huang ◽  
ying zhao ◽  
xiaoyan zhang ◽  
lu chen ◽  
...  

Abstract Background Chronic spontaneous urticaria (CSU) refers to recurrent urticaria that lasts for more than 6 weeks in the absence of an identifiable trigger. Due to its recurrent wheal and severe itching, CSU seriously affects patients' life quality. There is currently no radical cure for it and its vague pathogenesis limits the development of targeted therapy. With the goal of revealing the underlying mechanism, two data sets with accession numbers GSE57178 and GSE72540 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed genes (DEGs) of CSU skin lesion samples and healthy controls, four kinds of analyses were performed, namely functional annotation, protein-protein interaction (PPI) network and module construction, co-expression and drug-gene interaction prediction analysis, and immune and stromal cells deconvolution analyses. Results 92 up-regulated genes and 7 down-regulated genes were selected for subsequent analyses. Through the enrichment analysis of the core modules, three signal pathways were found to be closely related to the occurrence and development of CSU, including TNF signaling pathway, NF-κB signaling pathway and Jak-STAT signaling pathway. Referring to protein-protein interaction (PPI) network analysis and GeneCards database, we identified four key genes, IL6, TLR4, ICAM1, and PTGS2. In addition, according to the results of immune infiltration analysis, CSU tissue generally contained a higher proportion of dendritic cells, Th2 cells, mast cells, megakaryocyte-erythroid progenitor, preadipocytes, and macrophages M1. Conclusions To conclude, the key genes and pathways identified from CSU lesions and normal controls along with the immune infiltration profile may provide new insights into the development of CSU.


2020 ◽  
Author(s):  
Xinyue Chen ◽  
Lijun Hao

Abstract Background: Breast cancer (BC) is the most prevalent cancer among females globally. microRNAs (miRNAs) could regulate the expression levels of cancer-related genes through binding with target mRNAs. In various cancers, the abnormal expression of miR-130b has been detected. We aims to investigate the molecular mechanism and biological function of miR130b in breast cancer.Methods: We obtained two microRNA expression profiles from the Gene Expression Omnibus (GEO) database, including GSE45666 and GSE26659. We identified differentially expressed miRNAs (DE-miRNAs) between BC tissue and normal breast tissue based on the GEO2R web tool. DE-miRNAs were filtered by significant prognostic value resulting from Kaplan–Meier plotter. We used the JASPAR database to explore upstream regulators of miR-130b. The potential molecular mechanisms of miR-130b correlation genes were revealed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis in WebGestalt. Protein–protein interaction (PPI) network of miR-130b target genes was constructed by STRING. Cytoscape software was used to visualize the PPI network and hub genes.Results: miR-130b was highly expressed in breast cancer tissues, which positively correlates with poor prognostic. JASPAR revealed THAP11 might be the upstream regulator of miR-130b. In addition, GO, and KEGG pathway revealed that miR-130b positively regulated PFKP, STAT1, SRC, and NOTCH2, participating in the Thyroid hormone signaling pathway. The PPI network further identified that AR, KIT, and ESR1 as hub genes in BC development.Conclusion: miR-130b, which is regulated by THAP11, acts as an oncogene and prognostic biomarker in BC by mediating the Thyroid hormone signaling pathway and potential target genes. miR-130b might be a novel therapeutic target for BC treatment.


2021 ◽  
Author(s):  
Kai Huang ◽  
Bigyuan Lin ◽  
Haiyong Ren ◽  
Qifen Mao ◽  
Qiaofeng Guo ◽  
...  

Abstract Background:S. aureus (Staphylococcus aureus) infection imposes a serious burden to global healthcare systems. WWXDY (Wuweixiaoduyin) is a traditional Chinese medicine, and it is usually used to treat infections in China. This study aimed to explore the active compounds, therapeutic targets, key pathways, and potential mechanisms of WWXDY in the treatment of S. aureus infection. Materials & Methods:Data related to active compounds and therapeutic targets of WWXDY for treating S. aureus were collected from DisGeNET, GeneCards, and DrugBank databases. To explore the roles of the active targets in gene function and signaling pathways, KEGG (Kyoto Gene and Genomics Encyclopedia) pathway enrichment and GO (Gene Ontology) analyses of the 122 target genes in the PPI (protein-protein interaction) network were performed. We further performed NP (network pharmacology) by using a network analyzer to screen 30 key targets. Results:A total 92 active compounds of WWXDY were screened. The 122 overlapped genes were found from 785 therapeutic targets and 684 S. aureus-related genes. Besides, 92 active compounds of WWXDY, such as mandenol, ethyllinolenate, eriodyctiol, secologanic dibutylacetal_qt, etc., were identified. The PPI network of the effective ingredients of WWXDY in treating S. aureus infection identified the top 30 genes, including IL-6 (interleukin-6), TNF-α (tumor necrosis factor-α), VEGFA (vascular endothelial growth factor A), AKT1, CXCL8, MAPK3 (mitogen-activated protein kinase 3), TLR (toll-like receptor 4), IL-1β, EGFR (epidermal growth factor receptor), and MMP9 (matrix metalloproteinase-9). Conclusion:The GO functional and KEGG pathway enrichment analyses indicated that 122 overlapped genes were mainly enriched in COVID-19, AGE-RAGE signaling pathway, C-type lectin receptor signaling pathway, Pertussis, and Chagas disease. Our findings indicated the active compounds and therapeutic targets of WWXDY in treating S. aureus infection, as well as its potential mechanisms.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xuejiao Xie ◽  
Xingyu Ma ◽  
Siyu Zeng ◽  
Wansi Tang ◽  
Liucheng Xiao ◽  
...  

Atherosclerosis is a common metabolic disease characterized by lipid metabolic disorder. The processes of atherosclerosis include endothelial dysfunction, new endothelial layer formation, lipid sediment, foam cell formation, plaque formation, and plaque burst. Owing to the adverse effects of first-line medications, it is urgent to discover new medications to deal with atherosclerosis. Berberine is one of the most promising natural products derived from traditional Chinese medicine. However, the panoramic mechanism of berberine against atherosclerosis has not been discovered clearly. In this study, we used network pharmacology to investigate the interaction between berberine and atherosclerosis. We identified potential targets related to berberine and atherosclerosis from several databases. A total of 31 and 331 putative targets for berberine and atherosclerosis were identified, respectively. Then, we constructed berberine and atherosclerosis targets with PPI data. Berberine targets network with PPI data had 3204 nodes and 79437 edges. Atherosclerosis targets network with PPI data had 5451 nodes and 130891 edges. Furthermore, we merged the two PPI networks and obtained the core PPI network from the merged PPI network. The core PPI network had 132 nodes and 3339 edges. At last, we performed functional enrichment analyses including GO and KEGG pathway analysis in David database. GO analysis indicated that the biological processes were correlated with G1/S transition of mitotic cells cycle. KEGG pathway analysis found that the pathways directly associated with berberine against atherosclerosis were cell cycle, ubiquitin mediated proteolysis, MAPK signaling pathway, and PI3K-Akt signaling pathway. After combining the results in context with the available treatments for atherosclerosis, we considered that berberine inhibited inflammation and cell proliferation in the treatment of atherosclerosis. Our study provided a valid theoretical foundation for future research.


2021 ◽  
Vol 70 (7) ◽  
Author(s):  
Li Wang ◽  
Yuhe Wang ◽  
Wei Yang ◽  
Xue He ◽  
Shilin Xu ◽  
...  

Introduction. Coronavirus disease 2019 (COVID-19) is a highly contagious disease and ravages the world. Hypothesis/Gap Statement. We proposed that R. crenulata might have potential value in the treatment of COVID-19 patients by regulating the immune response and inhibiting cytokine storm. Aim. We aimed to explore the potential molecular mechanism for Rhodiola crenulata (R. crenulata), against the immune regulation of COVID-19, and to provide a referenced candidate Tibetan herb (R. crenulata) to overcome COVID-19. Methodology. Components and targets of R. crenulata were retrieved from the TCMSP database. GO analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were built by R bioconductor package to explore the potential biological effects for targets of R. crenulata. The R. crenulata-compound-target network, target pathway network and protein–protein interaction (PPI) network were constructed using Cytoscape 3.3.0. Autodock 4.2 and Discovery Studio software were applied for molecular docking. Result. Four bioactive components (quercetin, kaempferol, kaempferol-3-O-α-l-rhamnoside and tamarixetin) and 159 potential targets of R. crenulata were identified from the TCMSP database. The result of GO annotation and KEGG-pathway-enrichment analyses showed that target genes of R. crenulata were associated with inflammatory response and immune-related signalling pathways, especially IL-17 signalling pathway, and TNF signalling pathway. Targets-pathway network and PPI network showed that IL-6, IL-1B and TNF-α were considered to be hub genes. Molecular docking showed that core compound (quercetin) had a certain affinity with IL-1β, IL-6 and TNF-α. Conclusion. R. crenulata might play an anti-inflammatory and immunoregulatory role in the cytokine storm of COVID-19.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Haoxian Wang ◽  
Jihong Zhang ◽  
Qinqin Zhu ◽  
Xianyun Fu ◽  
Chenjie Li

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.


2021 ◽  
Author(s):  
JingJing Xiang ◽  
Chen-Jun Lin ◽  
Yu Zhang ◽  
Ni Zhu ◽  
Jian-Ping Shen ◽  
...  

Abstract Background: Strychnos nux-uomical (Ma Qianzi in pinyin), a classic chinese herb, has been extensively used to treat peripheral neuropathy in clinical practice in china for many years. However, the pharmacological mechanisms of strychnos nux-uomical remain vague. The aim of this study was to decrypt the underlying mechanisms of strychnos nux-uomical in the treatment of peripheral neuropathy using a systems harmacology approach.Methods: Using pharmacokinetic parameters [oral bioavailability (OB)≥30% and drug likeness (DL)≥0.18] of traditional chinese medicine system pharmacology platform (TCMSP) to screen the active ingredient of strychnos nux-uomical, and then integrating target prediction human gene database to predict and screen its target genes for the treatment of strychnos nux-uomical, network topology attribute analysis software cytoscape 3.6.0 was utilized to construct the active components-peripheral neuropath targets network. String database and cytoscape software were used to draw the protein interaction network. Finally gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses by panther database. Results: A total of 13 potential active ingredients were screened based on their OB and DL parameters, and 72 core targets were related to disease target. The results of pathway enrichment analysis indicated that putative targets of strychnos nux-uomical mostly participated in various pathways associated with cellular process, response to stimulus, biological regulation, metabolic process, localization. The putative targets of strychnos nux-uomical (endothelial growth factor, tumor necrosis factor-α, interleukin-10, interleukin-6, interleukin 1β and so on) were recognized as active factors involved in the main biological functions of treatment, which implied that these were involved in the underlying mechanisms of strychnos nux-uomical on peripheral neuropathy.Conclusions: In this study, a network pharmacology-based strategy integrating target prediction, network construction, GO and KEGG pathway enrichment analyses, was adopted to predict the targets of strychnos nux-uomical relevant to the treatment of peripheral neuropathy and to further explore the involved pharmacological mechanisms.


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