Mechanisms underlying the therapeutic effects of Xiaoyaosan in treating hyperplasia of mammary glands based on network pharmacology
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SUBMITTER: Li P
PROVIDER: S-EPMC10957003 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:Objective: Through network pharmacology and molecular docking technology, the hub genes, biological functions, and signaling pathways of 4-Octyl itaconate (4-OI) against sepsis were revealed. Methods: Pathological targets of sepsis were screened using GeneCards and GEO databases. Similarly, the pharmacological targets of 4-OI were obtained through Swiss TargetPrediction (STP), Similarity ensemble approach (SEA), and TargetNet databases. Then, all the potential targets of 4-OI anti-sepsis were screened by the online platform Draw Venn diagram, and the hub genes were screened by Cytoscape software. The identified hub genes were analyzed by GO and KEGG enrichment analysis, protein interaction (PPI) network, and molecular and docking technology to verify the reliability of hub gene prediction, further confirming the target and mechanism of 4-OI in the treatment of sepsis. Results: After the target screening of 4-OI and sepsis, 264 pharmacological targets, 1953 pathological targets, and 72 genes related to 4-OI anti-sepsis were obtained, and eight hub genes were screened, namely MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2, and HSP90AA1. The enrichment analysis results indicated that 4-OI might be involved in regulating inflammatory imbalance, immunosuppression, and oxidative stress in developing sepsis. 4-OI protects multiple organ dysfunction in sepsis by acting on hub genes, and MMP9 is a reliable gene for the prognosis and diagnosis of sepsis. The molecular docking results showed that 4-OI binds well to the hub target of sepsis. Conclusion: 4-OI plays an antiseptic role by regulating MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2 and HSP90AA1. These Hub genes may provide new insights into follow-up research on the target of sepsis treatment.
| S-EPMC9671214 | biostudies-literature
Project description:Aim of the studyThe aim of this study was to systematically investigate the effects and mechanisms of Rhubarb in the treatment of Atherosclerosis (AS) and Abdominal Aortic Aneurysm (AAA) by utilizing network pharmacology and molecular docking techniques.Materials and methodsTCMSP systematic pharmacology database was utilized to search for active chemical components of Rhubarb. Disease-related targets were retrieved from the GEO dataset and Disgenet database. Gene interactions were utilized to identify common targets of Rhubarb with AS/AAA, and interaction networks were constructed using Cytoscape 3.9.1. Protein-protein interaction (PPI) networks for the core targets were constructed using the STRING database. GO and KEGG pathway enrichment analysis was performed using DAVID. Molecular docking is used to assess the potential target-active compound interactions.ResultsIn our study, 16 active compounds were screened from Rhubarb, along with 310 targets. Additionally, 110 AS/AAA target genes were screened out. Topological analysis of the PPI protein network yielded 23 core targets. The targets, biological functions and signaling pathways of Rhubarb in AS/AAA were further investigated. The analysis indicated that Rhubarb may be effective in treating AS/AAA through processes such as lipids, atherosclerosis, extracellular matrix catabolism, collagenolytic metabolic processes, and the extracellular environment. Five core pharmacological targets were also identified: TNF, IL-1β MMP9, TP53, and PPARG. Molecular docking showed a strong binding ability between the active compounds and the screened targets.ConclusionsThis study successfully predicted the molecular functions, pharmacological targets, and pathways associated with Rhubarb for treating AS/AAA. In addition, identified potential active ingredients can be used as a source for AS/AAA drug screening.
| S-EPMC11867279 | biostudies-literature
Project description:BackgroundChinese medicine usually acts as "multi-ingredients, multi-targets and multi-pathways" on complex diseases, and these action modes reflect the coordination and integrity of the treatment process with traditional Chinese medicine (TCM). System pharmacology is developed based on the cross-disciplines of directional pharmacology, system biology, and mathematics, has the characteristics of integrity and synergy in the treatment process of TCM. Therefore, it is suitable for analyzing the key ingredients and mechanisms of TCM in treating complex diseases. Intracerebral Hemorrhage (ICH) is one of the leading causes of death in China, with the characteristics of high mortality and disability rate. Bring a significant burden on people and society. An increasing number of studies have shown that Chinese medicine prescriptions have good advantages in the treatment of ICH, and Ditan Decoction (DTT) is one of the commonly used prescriptions in the treatment of ICH. Modern pharmacological studies have shown that DTT may play a therapeutic role in treating ICH by inhibiting brain inflammation, abnormal oxidative stress reaction and reducing neurological damage, but the specific key ingredients and mechanism are still unclear.MethodsTo solve this problem, we established PPI network based on the latest pathogenic gene data of ICH, and CT network based on ingredient and target data of DTT. Subsequently, we established optimization space based on PPI network and CT network, and constructed a new model for node importance calculation, and proposed a calculation method for PES score, thus calculating the functional core ingredients group (FCIG). These core functional groups may represent DTT therapy for ICH.ResultsBased on the strategy, 44 ingredients were predicted as FCIG, results showed that 80.44% of the FCIG targets enriched pathways were coincided with the enriched pathways of pathogenic genes. Both the literature and molecular docking results confirm the therapeutic effect of FCIG on ICH via targeting MAPK signaling pathway and PI3K-Akt signaling pathway.ConclusionsThe FCIG obtained by our network pharmacology method can represent the effect of DTT in treating ICH. These results confirmed that our strategy of active ingredient group optimization and the mechanism inference could provide methodological reference for optimization and secondary development of TCM.
| S-EPMC9912606 | biostudies-literature
Project description:Hyperplasia of mammary glands (HMG) is common in middle-aged women. Danlu capsules (DLCs) can effectively relieve pain and improve clinical symptoms and are safe for treating HMG. However, the active substances in DLCs and the molecular mechanisms of DLCs in HMG remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of DLCs by using a systems pharmacology approach. The candidate compounds were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Each candidate's druggability was analyzed according to its oral bioavailability and drug-likeness indices. The candidate proteins and genes were extracted in the TCMSP and UniProt Knowledgebase, respectively. The potential pathways associated with the genes were identified by performing gene enrichment analysis with DAVID Bioinformatics Resources 6.7. A total of 603 compounds were obtained from DLCs, and 39 compounds and 66 targets associated with HMG were obtained. Gene enrichment analysis yielded 10 significant pathways with 34 targets. The integrated HMG pathway revealed that DLCs probably act in patients with HMG through multiple mechanisms of anti-inflammation, analgesic effects, and hormonal regulation. This study provides novel insights into the mechanisms of DLCs in HMG, from the molecular level to the pathway level.
| S-EPMC5460382 | biostudies-literature
Project description:BackgroundInfertility affects approximately 15% of couples around the world, and male factors are accounted for 40-50%. Oligoasthenozoospermia is the most common reason for male infertility. Unfortunately, effective drug therapy is still lacking except for assisted reproductive technology (ART). Previous researchers found that Wuzi Ershen decoction (WZESD) can increase sperm count, enhance sperm vitality, and improve semen quality. However, the pharmacological mechanisms remain unclear.MethodsIn this study, we screened compounds and predicted the targets of WZESD based on the TCMSP and BATMAN-TCM database combined with literature searching in the PubMed database. We obtained proteins related to oligoasthenozoospermia through GeneCards and submitted them to STRING to obtain the protein-protein interaction (PPI) network. Potential targets of WZESD were mapped to the network, and the hub targets were screened by topology. We used online platform Metascape and Enrichr for GO and KEGG enrichment analyses. AutoDock Vina was utilized for further verification of the binding mode between compounds and targets.ResultsTotally, 276 bioactive compounds were obtained and targeted 681 proteins. 446 oligoasthenozoospermia disease-specific proteins were acquired, and further bioinformatics analysis found that they were mainly involved in the formation of gametes, meiosis, and sperm differentiation. Protein interaction network analysis revealed that target proteins of WZESD were associated with oligoasthenozoospermia disease-specific proteins. The 79 targets of disease-specific proteins, which were anchored by WZESD, mainly participate in the cellular response to the organic cyclic compound, regulation of the apoptotic process, nitricoxide biosynthetic and metabolic process, oxidative stress, and protein phosphorylation regulation, which are the causes for oligoasthenozoospermia. Molecular docking simulation further validated that bioactive compounds originated from WZESD with targeted proteins showed high binding efficiency.ConclusionsThis study uncovers the therapeutic mechanisms of WZESD for oligoasthenozoospermia treatment from the perspective of network pharmacology and may provide a valuable reference for further experimental research studies and clinical applications.
| S-EPMC8363445 | biostudies-literature
Project description:Malignant melanoma is one of the most aggressive of cancers; if not treated early, it can metastasize rapidly. Therefore, drug therapy plays an important role in the treatment of melanoma. Cinobufagin, an active ingredient derived from Venenum bufonis, can inhibit the growth and development of melanoma. However, the mechanism underlying its therapeutic effects is unclear. The purpose of this study was to predict the potential targets of cinobufagin in melanoma. We gathered known and predicted targets for cinobufagin from four online databases. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were then performed. Gene expression data were downloaded from the GSE46517 dataset, and differential gene expression analysis and weighted gene correlation network analysis were performed to identify melanoma-related genes. Using input melanoma-related genes and drug targets in the STRING online database and applying molecular complex detection (MCODE) analysis, we identified key targets that may be the potential targets of cinobufagin in melanoma. Moreover, we assessed the distribution of the pharmacological targets of cinobufagin in melanoma key clusters using single-cell data from the GSE215120 dataset obtained from the Gene Expression Omnibus database. The crucial targets of cinobufagin in melanoma were identified from the intersection of key clusters with melanoma-related genes and drug targets. Receiver operating characteristic curve (ROC) analysis, survival analysis, molecular docking, and molecular dynamics simulation were performed to gain further insights. Our findings suggest that cinobufagin may affect melanoma by arresting the cell cycle by inhibiting three protein tyrosine/serine kinases (EGFR, ERBB2, and CDK2). However, our conclusions are not supported by relevant experimental data and require further study.
| S-EPMC10859445 | biostudies-literature
Project description:ContextHyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options.ObjectiveThis study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms.Materials and methodsWe employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD's hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an in vitro hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting.ResultsALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC50) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells.Discussion and conclusionTHSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.
| S-EPMC11632782 | biostudies-literature
Project description:Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.
| S-EPMC7884818 | biostudies-literature
Project description:Background and objectivesOn account of the long-term inflammatory microenvironment, diabetic wounds are challenging to heal in which advanced glycation end products are considered important factors hindering the healing of diabetic wounds. Gum Arabic has demonstrated significant potential in the treatment of various diseases owing to its anti-inflammatory and antioxidant properties. Nonetheless, there is still insufficient research on the role of Arabic gum in facilitating diabetic wounds healing and its mechanisms. This study aims to investigate the pharmacological targets and therapeutic mechanisms of Arabic Gum on diabetic wound healing by adopting network pharmacology, molecular docking, and experimental validation.MethodsKey active components of Arabic Gum and disease targets were identified through network pharmacology and bioinformatics. GO/KEGG enrichment was performed to identify critical pathways. Cytoscape and AutoDock were used for targets prediction and molecular docking validation. In vitro, Transwell assay and tube formation assay were performed to evaluate the effect of Arabic Gum on human fibroblasts migration and human umbilical vein endothelial cells angiogenesis. Western blotting analyzed Pro-caspase-1, ASC, NLRP3 and NF-κB pathway-related proteins. In vivo, a full-thickness diabetic wound model was established. Histological changes were assessed via H&E and Masson's staining, oxidative stress levels through DHE staining, inflammation levels with IL-1β, CD68 and CD206 staining, angiogenesis and cell proliferation levels were assessed by CD31 and Ki67 staining. The levels of pathway-related proteins were analyzed by NLRP3 and Phospho-NF-κB P65 staining.ResultsNetwork pharmacology analysis identified key targets, encompassing HSP90AA1, STAT3, and PRKCB, involved in the AGEs-NF-κB-NLRP3 signaling axis. Molecular docking demonstrated strong binding affinity between AG components and these targets. In vitro, AG lessened AGEs-induced activation of the NLRP3 inflammasome via modulation of the NF-κB pathway and reinforced cell migration and angiogenesis. In vivo, AG-treated diabetic wounds exhibited accelerated healing, with augmented collagen deposition, lowered oxidative stress and inflammation, and strengthened cell migration and angiogenesis. AG promotes diabetic wound healing by modulating the AGEs-NF-κB-NLRP3 axis, exerting anti-inflammatory, antioxidant, pro-angiogenic, and cell-proliferative effects.ConclusionThis study provides new insights into diabetic wound repair and suggests that AG is a promising therapeutic agent for improving diabetic wound healing.
| S-EPMC11882529 | biostudies-literature
Project description:PurposeTo uncover how the Huayu Quban (HYQB) capsule treats acne vulgaris (AV) through the use of network pharmacology and molecular docking technology.MethodsThe traditional Chinese medicine system pharmacology database (TCMSP) was used to identify the components and potential targets of HYQB capsule. Targets related to AV were identified by screening the GeneCards, Disease Gene Network (DisGeNET) and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network between targets of active ingredients and AV targets was built using the STRING database. Cytoscape3.7.2 software was used to create the visualization network for the 'herb-component-target' and identify the key targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized for functional enrichment analysis of the primary targets. Subsequently, molecular docking technology was employed to confirm the interaction between key components and core targets.ResultsThe technique discovered 50 different active substances and 270 associated therapeutic targets in the HYQB capsule as well as predicting 70 targets for treating acne vulgaris. Cytoscape hubba plug-in identified 19 key target genes, with the top 5 being TNF, IL1B, CCL2, SIRT1, IFNG, and IL10. Analysis of KEGG pathways revealed significant enrichment of immune-related pathways, including TNF and IL-17 signaling pathways, among the target genes. The HYQB capsule also involves lipid and atherosclerosis, Th17 cell differentiation, and the AGE-RAGE signaling pathway in diabetic complication signaling pathways. Molecular docking results showed that quercetin, luteolin, kaempferol, and wogonin, the core components of HYQB, had good binding ability with the first 4 core targets.ConclusionsThe HYQB capsule may have a synergistic effect on inhibiting sebaceous adipogenesis and sebum cell differentiation and play an effect on AV through anti-inflammatory and antioxidant effects of different signaling pathways.
| S-EPMC11743294 | biostudies-literature