Effect of Shan Zha (Hawthorn or Crataegus) on gastrointestinal cancer: A network pharmacology and molecular docking study
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ABSTRACT:
SUBMITTER: Yang J
PROVIDER: S-EPMC10846330 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Project description:Hawthorn leaves, which is a traditional Chinese medicine (TCM), has been used for treating coronary heart disease (CHD) for a long time in China. But the limited understanding of the main active components and molecular mechanisms of this traditional medicine has restricted its application and further research. The active compounds of hawthorn leaves were obtained from TCMSP database and SymMap database. The targets of it were predicted based on TCMSP, PubChem, Swiss Target Prediction, and SymMap database. The putative targets of CHD were gathered from multi-sources databases including the Online Mendelian Inheritance in Man (OMIM) database, the DrugBank database, the GeneCards database and the DisGeNet database. Network topology analysis, GO and KEGG pathway enrichment analyses were performed to select the key targets and pathways. Molecular docking was performed to demonstrate the binding capacity of the key compounds to the predicted targets. Furthermore, RAW264.7 cells stimulated by lipopolysaccharides (LPS) were treated with three effective compounds of hawthorn leaves to assess reliability of prediction. Quercetin, isorhamnetin and kaempferol were main active compounds in hawthorn leaves. Forty four candidate therapeutic targets were identified to be involved in protection of hawthorn leaves against CHD. Additionally, the effective compounds of it had good binding affinities to PTGS2, EGFR, and MMP2. Enrichment analyses suggested that immune inflammation related biological processes and pathways were possibly the potential mechanism. Besides, we found that three predicted effective compounds of hawthorn leaves decreased protein expression of PTGS2, MMP2, MMP9, IL6, IL1B, TNFα and inhibited activation of macrophage. In summary, the present study demonstrates that quercetin, kaempferol and isorhamnetin are proved to be the main effective compounds of hawthorn leaves in treatment of CHD, possibly by suppressing expression of PTGS2, MMP2, MMP9, inflammatory cytokines and macrophages viability. This study provides a new understanding of the active components and mechanisms of hawthorn leaves treating CHD from the perspective of network pharmacology.
| S-EPMC9243333 | biostudies-literature
Project description:BackgroundShanmei Capsule is a famous preparation in China. However, the related mechanism of Shanmei Capsule against hyperlipidemia has yet to be revealed.ObjectiveTo elucidate underlying mechanism of Shanmei Capsule against hyperlipidemia through network pharmacology approach and molecular docking.MethodsActive 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.ResultsSeventeen 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.ConclusionsThe 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.
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Project description:Extracts from the leaves and flowers of Crataegus spp. (i.e., hawthorn species) have been traditionally used with documented preclinical and clinical activities in cardiovascular medicine. Based on reported positive effects on heart muscle after ischemic injury and the overall cardioprotective profile, the present study addressed potential contributions of Crataegus extracts to cardiopoietic differentiation from stem cells. The quantified Crataegus extract WS®1442 stimulated cardiomyogenesis from murine and human embryonic stem cells (ESCs). Mechanistically, this effect was found to be induced by promoting differentiation of cardiovascular progenitor cell populations but not by proliferation. Bioassay-guided fractionation, phytochemical and analytical profiling suggested high-molecular weight ingredients as the active principle with at least part of the activity due to oligomeric procyanidines (OPCs) with a degree of polymerization between 3 and 6 (DP3-6). Transcriptome profiling in mESCs suggested two main, plausible mechanisms: These were early, stress-associated cellular events along with the modulation of distinct developmental pathways, including the upregulation of brain-derived neurotrophic factor (BDNF) and retinoic acid as well as the inhibition of transforming growth factor β/bone morphogenetic protein (TGFβ/BMP) and fibroblast growth factor (FGF) signaling. In addition, WS®1442 stimulated angiogenesis ex vivo in Sca-1+ progenitor cells from adult mice hearts. These in vitro data provide evidence for a differentiation promoting activity of WS®1442 on distinct cardiovascular stem/progenitor cells that could be valuable for therapeutic heart regeneration after myocardial infarction. However, the in vivo relevance of this new pharmacological activity of Crataegus spp. remains to be investigated and active ingredients from bioactive fractions will have to be further characterized.
| S-EPMC6902660 | biostudies-literature
Project description:Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.
| S-EPMC10392700 | biostudies-literature
Project description:Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD's pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.
| S-EPMC9423997 | biostudies-literature
Project description:Identification of key regulators is a critical step toward discovering biomarker that participate in BC. A gene expression dataset of breast cancer patients was used to construct a network identifying key regulators in breast cancer. Overexpressed genes were identified with BioXpress, and then curated genes were used to construct the BC interactome network. As a result of selecting the genes with the highest degree from the BC network and tracing them, three of them were identified as novel key regulators, since they were involved at all network levels, thus serving as the backbone. There is some evidence in the literature that these genes are associated with BC. In order to treat BC, drugs that can simultaneously interact with multiple targets are promising. When compared with single-target drugs, multi-target drugs have higher efficacy, improved safety profile, and are easier to administer. The haplotype and LD studies of the FN1 gene revealed that the identified variations rs6707530 and rs1250248 may both cause TB, and endometriosis respectively. Interethnic differences in SNP and haplotype frequencies might explain the unpredictability in association studies and may contribute to predicting the pharmacokinetics and pharmacodynamics of drugs using FN1.
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Project description:BackgroundTo investigate the pharmacological mechanism of Zhizhu pill (ZZP) against gastroesophageal reflux disease (GERD), network pharmacology in combination with molecular docking was applied in this study.MethodsActive compounds of ZZP and target genes related to GERD were identified through public databases. Subsequently, the obtained data were used as a basis for further network pharmacological analysis to explore the potential key active compounds, core targets, and biological processes involved in ZZP against GERD. Finally, the results predicted by network pharmacology were validated by molecular docking.ResultsTwenty active components of ZZP were identified to act on 59 targets related to GERD. Enrichment analysis revealed that multiple biological processes including response to oxygen levels, response to oxidative stress, and response to reactive oxygen species were involved in the GERD ZZP treatment with ZZP. ZZP had an impact on the prognosis of GERD mainly through the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and pathways in cancer. Further analysis identified the key components and core targets of ZZP against GERD, of which nobiletin, didymin, luteolin, and naringenin were key components, and PPARG, MMP9, JUN, TP53, PTGS2, EGFR, MAPK3, CASP3, AKT1, and VEGFA were the core targets. Molecular docking verified the stable bonds formed between the key components and the core targets.ConclusionsThe results of this study predict that the therapeutic effects of ZZP in GERD are mediated at least in part via PPARG, MMP9, JUN, TP53, PTGS2, EGFR, MAPK3, CASP3, AKT1, and VEGFA. These results may be useful in providing an experimental basis and new ideas for further research on ZZP in GERD.
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Project description:Hawthorn is of high economic value owing to its medicinal properties and health benefits. Crataegus is a member of the Rosaceae family; the genus has a complicated taxonomic history, and several theories on its origin have been proposed. In this study, 53 accessions from seven Crataegus taxa native to China and accessions of exotic Crataegus species (two from Europe and one from North America) were analyzed by specific locus amplified fragment sequencing (SLAF-seq). In total, 933,450 single-nucleotide polymorphisms were identified after filtering and used to investigate the species' genomic evolution. Phylogenetic trees derived from nuclear simple sequence repeats (SSRs) and SLAF-seq data showed the same topology, in which Crataegus maximowiczii and Crataegus sanguineae formed a closely related cluster that was clearly separated from the cluster composed of Crataegus hupehensis, Crataegus pinnatifida, Crataegus pinnatifida var. major, Crataegus bretschneideri and Crataegus scabrifolia. Phylogenetic and structure analysis indicated that the seven Chinese Crataegus taxa had two separate speciation events. Plants that evolved the southwestern route shared the genepool with the European species, whereas plants along the northeastern route shared the genepool with the North American species. TreeMix genetic analysis revealed that C. bretschneideri may have a hybrid origin. This study provides valuable information on the origins of Chinese Crataegus and suggests an evolutionary model for the main Crataegus species that native to China.
| S-EPMC6465762 | biostudies-literature
Project description:Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.
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Project description:Epithelial ovarian cancer (EOC) is one of the deadliest reproductive tract malignancies that form on the external tissue covering of an ovary. Cassia fistula is popular for its anti-inflammatory and anticarcinogenic properties in conventional medications. Nevertheless, its molecular mechanisms are still unclear. The current study evaluated the potential of C. fistula for the treatment of EOC using network pharmacology approach integrated with molecular docking. Eight active constituents of C. fistula were obtained from two independent databases and the literature, and their targets were retrieved from the SwissTargetPrediction. In total, 1077 EOC associated genes were retrieved from DisGeNET and GeneCardsSuite databases, and 800 potential targets of eight active constituents of C. fistula were mapped to the 1077 EOC targets and intersected targets from two databases. Ultimately, 98 potential targets were found from C. fistula for EOC. Finally, the protein-protein interaction network (PPI) topological interpretation revealed AKT1, CTNNB1, ESR1, and CASP3 as key targets. This is the first time four genes have been found against EOC from C. fistula. The major enriched pathways of these candidate genes were established by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) investigations. To confirm the network pharmacology findings, the molecular docking approach demonstrated that active molecules have higher affinity for binding to putative targets for EOC suppression. More pharmacological and clinical research is required for the development of a drug to treat EOC.
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