Dataset Information

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis.

ABSTRACT: Hepatoma is one of the most common malignant tumors. The incidence rate is high in developing countries, and China has the most significant number of cases. Dahuang is a classic traditional antitumor drug commonly used in China and has also been applied to treat hepatoma. However, the potential mechanism of Dahuang in treating hepatoma is not clear. Therefore, this study is aimed at elucidating the possible molecular mechanism and key targets of Dahuang using methods of network pharmacology, molecular docking, and survival analysis. Firstly, the active ingredients and key targets of Dahuang were analyzed through public databases, and then the drug-ingredient-target-disease network diagram of Dahuang against hepatoma was constructed. Five main active components and five core targets were determined according to the enrichment degree. Enrichment analysis demonstrated that Dahuang treated hepatoma through the multiple pathways in cancer. Additionally, molecular docking predicted that aloe-emodin and PIK3CG depicted the best binding energy. Survival analysis indicated that a high/ESR1 gene expression had a relatively good prognosis for patients with hepatoma (p < 0.05). In conclusion, the current study results demonstrated that Dahuang could treat hepatoma through a variety of active ingredients, targets, and multiantitumor pathways. Moreover, it effectively improved the prognosis of hepatoma patients. ESR1 is the potential key gene that is beneficial for the survival of hepatoma patients. Also, aloe-emodin and beta-sitosterol are the two main active crucial ingredients for hepatoma treatment. The study also provided some functional bases and references for the development of new drugs, target mining, and experimental animal research of hepatoma in the future.

SUBMITTER: Yu B

PROVIDER: S-EPMC9307382 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveTo elucidate the main mechanism of Xijiao Dihuang decoction (XJDHT) for the treatment of systemic lupus erythematosus (SLE).MethodsTCMSP, BATMAN-TCM, ETCM, and TCMID databases and literature search were used to screen the potential active compounds of XJDHT, and TCMSP and SwissProt databases were searched to predict the targets of the compounds. The targets of SLE were obtained from Genegards, OMIM, and DisGeNET databases, and Venn online platform was used to obtain the intersection targets of XJDHT and SLE. Afterwards, the PPI network was constructed by using the STRING database, and the core targets were identified by network topology analysis. GO and KEGG enrichment analyses were performed through R software, and molecular docking of the top three core targets and their corresponding compounds were accomplished by Autodock Vina and Pymol softwares.ResultsThere were 30 potential active ingredients, 289 potential targets, and 129 intersection targets screened from the above databases. Network topology analysis identified 23 core targets, such as AKT1, TNF, IL6, IL1B, and INS. GO enrichment analysis obtained 2555 terms and mainly clustering on the react to lipopolysaccharide, membrane raft, and ubiquitin-like protein ligase binding. KEGG enrichment analysis obtained 187 signaling pathways, mainly concentrating on the lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis. Molecular docking verified that the active compounds of XJDHT have the strong binding activity to the core targets.ConclusionThis study preliminarily uncovers the mechanism of XJDHT acting on SLE through a "multicompound, multitarget, and multipathway" manner. XJDHT may achieve the treatment of SLE by inhibiting the proinflammatory factors, inflammatory signal cvtokines, proliferation, injury, and apoptosis processes. In summary, the present study would provide a promising theoretical basis for further clinical and experimental studies.

Project description:ObjectiveTo explore the main bioactive compounds and investigate the underlying mechanism of Pollen Typhae (PT) against diabetic retinopathy (DR) by network pharmacology and molecular docking analysis.MethodsBioactive ingredients and the target proteins of PT were obtained from TCMSP, and the related target genes were acquired from the SwissTargetPrediction database. The target genes of DR were obtained from GeneCards, TTD database, DisGeNET database, and DrugBank. The compound-target interaction network was established based on Cytoscape 3.7.2. The protein-protein interaction (PPI) network was constructed via STRING database and Cytoscape 3.7.2. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were visualized through DAVID database and Bioinformatics. Ingredient-gene-pathway network analysis was conducted to further screen the ingredients, target proteins, and pathways closely related to the biological mechanism on PT for DR, and molecular docking analysis was performed by SYBYL-X 2.1.1 software. Finally, the mechanism and underlying targets of PT in the treatment of DR were predicted.ResultsA total of 8 compounds and 171 intersection targets were obtained based on the online network database. 7 main compounds were screened from compound-target network, and 53 targets including the top six key targets (PTGS2, AKT1, VEGFA, MAPK3, TNF, and EGFR) were further acquired from PPI analysis. The 53 key targets covered 80 signaling pathways, among which PI3K-Akt signaling pathway, focal adhesion, Rap1 signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway were closely connected with the biological mechanism involved in the alleviation of DR by PT. Ingredient-gene-pathway network shows that AKTI, EGFR, and VEGFA were core genes, kaempferol and isorhamnetin were pivotal ingredients, and VEGF signaling pathway and Rap1 signaling pathway were closely involved in anti-DR. The docking results indicated that five main compounds (arachidonic acid, isorhamnetin, quercetin, kaempferol, and (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one) had good binding activity with EGFR and AKT1 targets.ConclusionThe active ingredients in PT may regulate the levels of inflammatory factors, suppress the oxidative stress, and inhibit the proliferation, migration, and invasion of retinal pericytes by acting on PTGS2, AKT1, VEGFA, MAPK3, TNF, and EGFR targets through VEGF signaling pathway, PI3K-Akt signaling pathway, Rap1 signaling pathway, and HIF-1 signaling pathway to play a therapeutic role in diabetic retinopathy.

Project description:Acute kidney injury (AKI) is a severe and frequent complication of sepsis that occurs in intensive care units with inflammation and rapid decline in renal function as the main pathological features. Systemic inflammation, microvascular dysfunction, and tubule injury are the main causes of sepsis-induced AKI (SI-AKI). The high prevalence and death rate from SI-AKI is a great challenge for clinical treatment worldwide. However, in addition to hemodialysis, there is no effective drug to improve renal tissue damage and alleviate the decline in kidney function. We conducted a network pharmacological analysis of Salvia miltiorrhiza (SM), a traditional Chinese medicine, which is widely used for the treatment of kidney disease. Then, we combined molecular docking and a dynamics simulation to screen for the active monomer dehydromiltirone (DHT) that has therapeutic effects on SI-AKI and investigated its potential mechanism of action through experimental validation. The components and targets of SM were obtained by searching the database, and 32 overlapping genes were screened by intersection analysis with AKI targets. GO and KEGG data showed that the functions of a common gene were closely related to oxidative stress, mitochondrial function, and apoptosis. The molecular docking results combined with molecular dynamics simulations provide evidence for a binding model between DHT and cyclooxygenase-2 (COX2), both of which are mainly driven by van der Waals interactions and a hydrophobic effect. In vivo, we found that mice pretreated with an intraperitoneal injection of DHT (20 mg/kg/d) for 3 days ameliorated CLP surgery-induced renal function loss and renal tissue damage and inhibited inflammatory mediators IL-6, IL-1β, TNF-α, and MCP-1 production. In vitro, the DHT pretreatment decreased LPS-induced expression of COX2, inhibited cell death and oxidative stress, alleviated mitochondrial dysfunction, and restrained apoptosis in HK-2 cells. Our research indicates that the renal preventive effect of DHT is related to maintaining mitochondrial dynamic balance, restoring mitochondrial oxidative phosphorylation, and inhibiting cell apoptosis. The findings in this study provide a theoretical basis and a novel method for the clinical therapy of SI-AKI.

Project description:In this study, we predicted the core active compounds of Huangqi Guizhi Wuwu decoction in treatment of oxaliplatin-induced peripheral neuropathy and the related potential mechanism. Corresponding database was used to complete the interaction (PPI) network of key targets and the enrichment analysis of corresponding genmes. Molecular docking of key targets and key compounds was carried out using relevant software. The 60 chemical components corresponding to the oral absorption of Huangqi Guizhi Wuwu decoction correspond to 157 unique targets, and the 233 chemical components corresponding to percutaneous absorption in vitro correspond to 155 unique targets. There were 1074 unique targets for chemotherapy-induced peripheral neuropathy. Finally, three common key targets (SLC6A2, SLC6A3, and SLC6A4) and two key compounds (6-Gingerol and nuciferin) were screened according to the above three target datasets. The results showed that The PPI network of common key targets involved 23 associated proteins. In the related GO enrichment results, there were 33 items related to biological processes, 13 items related to cell composition, 21 items related to molecular function, and four KEGG pathway enrichments. L1000 kinase and GPCR perturbation analysis showed that the associated protein had an effect on the expression of multiple groups of kinase genes. HPA revealed that the enrichment of three common key targets was tissue-specific. The docking results showed that the 6 groups were structurally stable. The oral and topical use of Huangqi Guizhi Wuwu decoction can prevent and control peripheral neurotoxicity. The prevention and control effects may be related to its participation in the regulation of neurotransmitter transport, sympathetic activity, and transport. The histological parts of the mechanism are mainly distributed in the adrenal gland, placenta, brain, intestine, and lung, the blood is not specific. According to the prediction results of molecular docking, 6-Gingerol and nuciferin can closely bind to three common key targets.

Dataset Information

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets