Dataset Information

Combining Network Pharmacology and Experimental Validation to Study the Action and Mechanism of Water extract of Asparagus Against Colorectal Cancer.

ABSTRACT: Asparagus (ASP) is a well-known traditional Chinese medicine with nourishing, moistening, fire-clearing, cough-suppressing, and intestinal effects. In addition, it exerts anti-inflammatory, antioxidant, anti-aging, immunity-enhancing, and anti-tumor pharmacological effect. The anti-tumor effect of ASP has been studied in hepatocellular carcinoma. However, its action and pharmacological mechanism in colorectal cancer (CRC) are unclear. The present study aimed to identify the potential targets of ASP for CRC treatment using network pharmacology and explore its possible therapeutic mechanisms using in vitro and in vivo experiments. The active compounds and potential targets of ASP were obtained from the TCMSP database, followed by CRC-related target genes identification using GeneCards and OMIM databases, which were matched with the potential targets of ASP. Based on the matching results, potential targets and signaling pathways were identified by protein-protein interaction (PPI), gene ontology (GO) functions, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, in vitro and in vivo experiments were performed to further validate the anti-cancer effects of ASP on CRC. Network pharmacology analysis identified nine active components from ASP from the database based on oral bioavailability and drug similarity index, and 157 potential targets related to ASP were predicted. The PPI network identified tumor protein 53 (TP53), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and AKT serine/threonine kinase 1 (AKT1) as key targets. GO analysis showed that ASP might act through response to wounding, membrane raft, and transcription factor binding. KEGG enrichment analysis revealed that ASP may affect CRC through the phosphatidylinositol-4,5-bisphosphate 3-kinase PI3K/AKT/mechanistic target of rapamycin kinase (mTOR) signaling pathway. In vitro, ASP inhibited cell proliferation, migration, and invasion of HCT116 and LOVO cells, and caused G0/G1 phase arrest and apoptosis in CRC cells. In vivo, ASP significantly inhibited the growth of CRC transplanted tumors in nude mice. Furthermore, pathway analysis confirmed that ASP could exert its therapeutic effects on CRC by regulating cell proliferation and survival through the PI3K/AKT/mTOR signaling pathway. This study is the first to report the potential role of ASP in the treatment of colorectal cancer.

SUBMITTER: Liang H

PROVIDER: S-EPMC9237230 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundObesity, a condition associated with the development of widespread cardiovascular disease, metabolic disorders, and other health complications, has emerged as a significant global health issue. Oleanolic acid (OA), a pentacyclic triterpenoid compound that is widely distributed in various natural plants, has demonstrated potential anti-inflammatory and anti-atherosclerotic properties. However, the mechanism by which OA fights obesity has not been well studied.MethodNetwork pharmacology was utilized to search for potential targets and pathways of OA against obesity. Molecular docking and molecular dynamics simulations were utilized to validate the interaction of OA with core targets, and an animal model of obesity induced by high-fat eating was then employed to confirm the most central of these targets.ResultsThe network pharmacology study thoroughly examined 42 important OA targets for the treatment of obesity. The key biological processes (BP), cellular components (CC), and molecular functions (MF) of OA for anti-obesity were identified using GO enrichment analysis, including intracellular receptor signaling, intracellular steroid hormone receptor signaling, chromatin, nucleoplasm, receptor complex, endoplasmic reticulum membrane, and RNA polymerase II transcription Factor Activity. The KEGG/DAVID database enrichment study found that metabolic pathways, PPAR signaling pathways, cancer pathways/PPAR signaling pathways, insulin resistance, and ovarian steroidogenesis all play essential roles in the treatment of obesity and OA. The protein-protein interaction (PPI) network was used to screen nine main targets: PPARG, PPARA, MAPK3, NR3C1, PTGS2, CYP19A1, CNR1, HSD11B1, and AGTR1. Using molecular docking technology, the possible binding mechanism and degree of binding between OA and each important target were validated, demonstrating that OA has a good binding potential with each target. The molecular dynamics simulation's Root Mean Square Deviation (RMSD), and Radius of Gyration (Rg) further demonstrated that OA has strong binding stability with each target. Additional animal studies confirmed the significance of the core target PPARG and the core pathway PPAR signaling pathway in OA anti-obesity.ConclusionOverall, our study utilized a multifaceted approach to investigate the value and mechanisms of OA in treating obesity, thereby providing a novel foundation for the identification and development of natural drug treatments.

Project description:Background: Paeoniflorin (PF) is the main active component of Chinese herbaceous peony that has been shown to have an anti-tumor effect. However, there are few studies on the prevention and treatment of pancreatic cancer with PF. Methods: We gathered Microarray data pertaining to paeoniflorin intervention in pancreatic cancer by utilizing the GEO database (GSE97124). Then, the DEGs were filtered by the 33R program. RNA-seq data of pancreatic cancer and normal tissue samples were taken from the TCGA and GTEx databases, respectively, and the WGCNA technique was utilized to examine the pancreatic cancer-specific genes. Paeoniflorin target genes for the treatment of pancreatic cancer were determined based on the overlap between DEGs and WGCNA. GO and KEGG enrichment analyses were then performed on paeoniflorin target genes to discover which biological processes were impacted. Using the 3 hierarchical methods included in the Cytohubba plugin, we re-screened the hub genes in the target genes to find the genes most relevant to paeoniflorin treatment. The overall survival effects of hub genes were confirmed using the TCGA database. Finally, the paeoniflorin targets identified by the network pharmacology analysis were validated using PANC-1 and Capan-2 cells. Results: We identified 148 main potential PF targets, and gene enrichment analysis suggested that the aforementioned targets play a crucial role in the regulation of MAPK, PI3K-AKT, and other pathways. The further screening of the prospective targets resulted in the identification of 39 hub genes. Using the TCGA database, it was determined that around 33.33% of the hub gene's high expression was linked with a bad prognosis. Finally, we demonstrated that PF inhibits IL-6 and IL-10 expression and p38 phosphorylation in pancreatic cancer cells, thereby reducing inflammation. Conclusion: PF may regulate inflammatory factors mainly through the p38 MAPK signal pathway. These findings provide theoretical and experimental evidence suggesting the PF as a promising natural source of anti-tumor compounds for pancreatic cancer.

Project description:ObjectiveBazhen Decoction (BZD) is a common adjuvant therapy drug for colorectal cancer (CRC), although its anti-tumor mechanism is unknown. This study aims to explore the core components, key targets, and potential mechanisms of BZD treatment for CRC.MethodsThe Traditional Chinese Medicine Systems Pharmacology (TCMSP) was employed to acquire the BZD's active ingredient and targets. Meanwhile, the Drugbank, Therapeutic Target Database (TTD), DisGeNET, and GeneCards databases were used to retrieve pertinent targets for CRC. The Venn plot was used to obtain intersection targets. Cytoscape software was used to construct an "herb-ingredient-target" network and identify core targets. GO and KEGG pathway enrichment analyses were conducted using R language software. Molecular docking of key ingredients and core targets of drugs was accomplished using PyMol and Autodock Vina software. Cell and animal research confirmed Bazhen Decoction efficacy and mechanism in treating colorectal cancer.ResultsBZD comprises 173 effective active ingredients. Using four databases, 761 targets related to CRC were identified. The intersection of BZD and CRC yielded 98 targets, which were utilized to construct the "herb-ingredient-target" network. The four key effector components with the most targets were quercetin, kaempferol, licochalcone A, and naringenin. Protein-protein interaction (PPI) analysis revealed that the core targets of BZD in treating CRC were AKT1, MYC, CASP3, ESR1, EGFR, HIF-1A, VEGFR, JUN, INS, and STAT3. The findings from molecular docking suggest that the core ingredient exhibits favorable binding potential with the core target. Furthermore, the GO and KEGG enrichment analysis demonstrates that BZD can modulate multiple signaling pathways related to CRC, like the T cell receptor, PI3K-Akt, apoptosis, P53, and VEGF signaling pathway. In vitro, studies have shown that BZD dose-dependently inhibits colon cancer cell growth and invasion and promotes apoptosis. Animal experiments have shown that BZD treatment can reverse abnormal expression of PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53 genes. BZD also increases the ratio of CD4+ T cells to CD8+ T cells in the spleen and tumor tissues, boosting IFN-γ expression, essential for anti-tumor immunity. Furthermore, BZD has the potential to downregulate the PD-1 expression on T cell surfaces, indicating its ability to effectively restore T cell function by inhibiting immune checkpoints. The results of HE staining suggest that BZD exhibits favorable safety profiles.ConclusionBZD treats CRC through multiple components, targets, and metabolic pathways. BZD can reverse the abnormal expression of genes such as PI3K, AKT, MYC, EGFR, HIF-1A, VEGFR, JUN, STAT3, CASP3, and TP53, and suppresses the progression of colorectal cancer by regulating signaling pathways such as PI3K-AKT, P53, and VEGF. Furthermore, BZD can increase the number of T cells and promote T cell activation in tumor-bearing mice, enhancing the immune function against colorectal cancer. Among them, quercetin, kaempferol, licochalcone A, naringenin, and formaronetin are more highly predictive components related to the T cell activation in colorectal cancer mice. This study is of great significance for the development of novel anti-cancer drugs. It highlights the importance of network pharmacology-based approaches in studying complex traditional Chinese medicine formulations.

Dataset Information

Combining Network Pharmacology and Experimental Validation to Study the Action and Mechanism of Water extract of Asparagus Against Colorectal Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets