Network Pharmacology and Molecular Docking-Based Prediction of the Mechanism of Qianghuo Shengshi Decoction against Rheumatoid Arthritis.
Ontology highlight
ABSTRACT:
SUBMITTER: Zeng Z
PROVIDER: S-EPMC8437630 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Background: Dingji Fumai Decoction (DFD), a traditional herbal mixture, has been widely used to treat arrhythmia in clinical practice in China. However, the exploration of the active components and underlying mechanism of DFD in treating atrial fibrillation (AF) is still scarce. Methods: Compounds of DFD were collected from TCMSP, ETCM, and literature. The targets of active compounds were explored using SwissTargetPrediction. Meanwhile, targets of AF were collected from DrugBank, TTD, MalaCards, TCMSP, DisGeNET, and OMIM. Then, the H-C-T-D and PPI networks were constructed using STRING and analyzed using CytoNCA. Meanwhile, VarElect was utilized to detect the correlation between targets and diseases. Next, Metascape was employed for systematic analysis of the mechanism of potential targets and protein complexes in treating AF. AutoDock Vina, Pymol, and Discovery Studio were applied for molecular docking. Finally, the main findings were validated through molecular biology experiments. Results: A total of 168 active compounds and 1,093 targets of DFD were collected, and there were 89 shared targets between DFD and AF. H-C-T-D network showed the relationships among DFD, active compounds, targets, and AF. Three functional protein complexes of DFD were extracted from the PPI network. Further systematic analysis revealed that the regulation of cardiac oxidative stress, cardiac inflammation, and cardiac ion channels were the potential mechanism of DFD in treating AF. Addtionally, molecular docking verified the interactions between active compounds and targets. Finally, we found that DFD significantly increased the level of SIRT1 and reduced the levels of ACE, VCAM-1, and IL-6. Conclusions: DFD could be utilized in treating AF through a complicated mechanism, including interactions between related active compounds and targets, promoting the explanation and understanding of the molecular biological mechanism of DFD in the treatment of AF.
| S-EPMC8631917 | biostudies-literature
Project description:ObjectiveThis study aimed to explore the mechanism of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis via a combination of network pharmacology and molecular docking.MethodsThe main chemical components and corresponding targets of Modified Danggui Sini Decoction were searched and screened in TCMSP database. The disease targets of knee osteoarthritis were summarized in GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. The visual interactive network of "drugs-active components-disease targets" was drawn by Cytoscape 3.8.1 software. The protein-protein interaction network was constructed by STRING database. Then, GO function and KEGG pathway enrichment were analyzed by Bioconductor/R, and the pathway of the highest degree of correlation with knee osteoarthritis was selected for specific analysis. Finally, molecular docking was used to screen and verify core genes by AutoDockTools software.ResultsSeventy-one main components of Modified Danggui Sini Decoction and 116 potential therapeutic targets of knee osteoarthritis were selected. The KEGG pathway and the GO function enrichment analysis showed that the targets of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis were mainly concentrated on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway, and NF-κB signaling pathway. It mainly involved inflammatory reaction, regulation of apoptotic signaling pathway, cellular response to regulation of inflammatory response, cellular response to oxidative stress, and other biological processes. The molecular docking results showed that ESR1-wogonin, MAPK1-quercetin, RELA-wogonin, RELA-baicalein, TP53-baicalein, TP53-quercetin, and RELA-quercetin have strong docking activities.ConclusionModified Danggui Sini Decoction has the hierarchical network characteristics of "multicomponent, multitarget, multifunction, and multipathway" in the treatment of knee osteoarthritis. It mainly regulates the proliferation and apoptosis of chondrocytes by regulating the PI3K-Akt signaling pathway and establishes cross-talk with many downstream inflammatory-related pathways to reduce the overall inflammatory response. Meanwhile, HIF-1 expression was used to ensure the normal function and metabolism of knee joint under hypoxia condition, and the above processes play a key role in the treatment of knee osteoarthritis.
| S-EPMC7895562 | biostudies-literature
Project description:BackgroundCisplatin is a frequently used and effective chemotherapy drug in clinical practice, but severe side effects limit its use, among which nephrotoxicity is considered the most serious and prolonged damage to the body. Astragalus membranaceus (AM) is a well-known herbal medicine, and modern pharmacological studies have confirmed its antioxidant, immunomodulatory, and antiapoptotic effects. Clinical studies have shown that AM and its active components can attenuate cisplatin-induced kidney damage, but the molecular mechanism has not been fully expounded.Materials and methodsFirst, the components and targets information of AM were collected from the TCMSP, and the relevant targets of cisplatin-induced kidney damage were accessed from the GeneCards and OMIM databases. Then, the core targets were selected by the Venn diagram and network topology analysis, which was followed by GO and KEGG pathway enrichment analysis. Finally, we construct a component-target-pathway network. Furthermore, molecular docking was carried out to identify the binding activity between active components and key targets.ResultsA total of 20 active components and 200 targets of AM and 646 targets related to cisplatin-induced kidney damage were obtained. 91 intersection targets were found between AM and cisplatin-induced kidney damage. Then, 16 core targets were identified, such as MAPK1, TNF-α, and p53. Furthermore, GO and KEGG pathway enrichment analysis suggested that MAPK, Toll-like receptor, and PI3K-Akt signaling pathways may be of significance in the treatment of cisplatin-induced kidney damage by AM. Molecular docking indicated that quercetin and kaempferol had high binding affinities with many core targets.ConclusionIn summary, the active components, key targets, and signaling pathways of AM in the treatment of cisplatin-induced kidney damage were predicted in this study, which contributed to the development and application of AM.
| S-EPMC8390139 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) is a new global public health emergency. The therapeutic benefits of Cold‒Damp Plague Formula (CDPF) against COVID-19, which was used to treat "cold‒dampness stagnation in the lung" in Trial Versions 6 and 7 of the "Diagnosis and Treatment Protocol for COVID-19", have been demonstrated, but the effective components and their mechanism of action remain unclear.MethodsIn this study, a network pharmacology approach was employed, including drug-likeness evaluation, oral bioavailability prediction, protein‒protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and virtual docking, to predict the bioactive components, potential targets, and molecular mechanism of CDPF for COVID-19 treatment.ResultsThe active compound of herbs in CDPF and their candidate targets were obtained through database mining, and an herbs-ingredients-targets network was constructed. Subsequently, the candidate targets of the active compounds were compared to those relevant to COVID-19, to identify the potential targets of CDPF for COVID-19 treatment. Subsequently, the PPI network was constructed, which provided a basis for cluster analysis and hub gene screening. The seed targets in the most significant module were selected for further functional annotation. GO enrichment analysis identified four main areas: (1) cellular responses to external stimuli, (2) regulation of blood production and circulation, (3) free radical regulation, (4) immune regulation and anti-inflammatory effects. KEGG pathway analysis also revealed that CDPF could play pharmacological roles against COVID-19 through "multi components‒multi targets‒multi pathways" at the molecular level, mainly involving anti-viral, immune-regulatory, and anti-inflammatory pathways; consequently, a "CDPF-herbs-ingredients-targets-pathways-COVID-19" network was constructed. In hub target analysis, the top hub target IL6, and ACE2, the receptor via which SARS-CoV-2 typically enters host cells, were selected for molecular docking analyses, and revealed good binding activities.ConclusionsThis study revealed the active ingredients and potential molecular mechanism by which CDPF treatment is effective against COVID-19, and provides a reference basis for the wider application and further mechanistic investigations of CDPF in the fight against COVID-19.
| S-EPMC7391051 | biostudies-literature
Project description:Huang-Lian-Jie-Du decoction (HLJDD) has been used to treat pneumonia for thousands of years in China. However, our understanding of its mechanisms on treating pneumonia is still unclear. In the present work, network pharmacology was used to analyze the potential active ingredients and molecular mechanisms of HLJDD on treating pneumonia. A total of 102 active ingredients were identified from HLJDD, among which 54 were hit by the 69 targets associated with pneumonia. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we obtained the main pathways associated with pneumonia and those associated with the mechanism of HLJDD in the treatment of pneumonia. By constructing the protein-protein interaction network of common targets, 10 hub genes were identified, which were mainly involved in the tumor necrosis factor (TNF) signaling pathway, interleukin 17 (IL-17) signaling pathway, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Moreover, the results of molecular docking showed that the active ingredients of HLJDD had a good affinity with the hub genes. The final results indicate that HLJDD has a greater effect on bacterial pneumonia than on viral pneumonia. The therapeutic effect is mainly achieved by regulating the host immune inflammatory response and oxidative stress reaction, antibacterial microorganisms, alleviating the clinical symptoms of pneumonia, repairing damaged cells, and inhibiting cell migration.
| S-EPMC7930397 | biostudies-literature
Project description:Danshen (Salvia miltiorrhiza Bunge), a natural powerful drug for various conditions treatment, has traditionally been used in Asian countries for centuries as anticancer agent, anti-inflammatory agent, and antioxidant. More recently, it is explored in combination with other herbs for skeletal diseases therapy; bone-targeting compounds with pharmacological activities have been isolated from various sources of traditional Chinese medicine (TCM), including Danshen. In this case, some evidence supports that Danshen may treat myelofibrosis (MF) by exerting its antitumor effect. To study the specific mechanism of Danshen in the treatment of MF, we used bioinformatics databases to determine its active ingredients. Then, identification of target proteins related to MF was made using a network pharmacology analysis platform. In our results, 20 key active compounds and 457 key targets of Danshen were identified. In-depth network analysis of the top diseases, functions, and pathways suggested that a common underlying mechanism linked Danshen involvement with MF. Finally, 5 potential targets were confirmed by the analysis; these 5 targets, as well as 20 previously identified compounds, were subjected to molecular docking experiments. The results indicated that cryptotanshinone of Danshen may affect MF by acting on the key genes in the JAK-STAT signalling pathway and the TGF-? signalling pathway.
| S-EPMC6304517 | biostudies-literature
Project description:Purpose: This study aimed to explore underlying action mechanism of Wu-Tou decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology prediction and experimental verification. Methods: Chemical compounds and human target proteins of WTD as well as RA-related human genes were obtained from TCM Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular networks and canonical pathways presumably involved in the treatment of WTD on RA were generated by ingenuity pathway analysis (IPA) software. Furthermore, experimental validation was carried out with MIP-1?-induced U937 cell model and collagen induced arthritis (CIA) rat model. Results: CCR5 signaling pathway in macrophages was shown to be the top one shared signaling pathway associated with both cell immune response and cytokine signaling. In addition, protein kinase C (PKC) ? and p38 in this pathway were treated as target proteins of WTD in RA. In vitro experiments indicated that WTD inhibited MIP-1?-induced production of TNF-?, MIP-1?, and RANTES as well as phosphorylation of CCR5, PKC ?, and p38 in U937 cells. WTD treatment maintained the inhibitory effects on production of TNF-? and RANTES in MIP-1?-induced U937 cells after CCR5 knockdown. In vivo experiments demonstrated that WTD ameliorated symptoms in CIA rats, decreased the levels of IL-1?, IL-2, IL-6, TNF-?, MIP-1?, MIP-2, RANTES, and IP-10 in serum of CIA rats, as well as mRNA levels of MIP-1?, MIP-2, RANTES, and IP-10 in ankle joints of CIA rats. Furthermore, WTD also lowered the phosphorylation levels of CCR5, PKC ? and p38 in both ankle joints and macrophages in ankle joints from CIA rats. Conclusion: It was demonstrated in this research that WTD played a role in inhibiting inflammatory response in RA which was closely connected with the modulation effect of WTD on CCR5 signaling pathway in macrophages.
| S-EPMC5414545 | biostudies-literature
Project description:Our goal was to explore the bioactive constituents of Longsheyangquan (LSYQ) Decoction and elucidate its mechanisms on the treatment of bladder cancer (BCa). A total of 38 compounds were selected based on their pharmacokinetic properties in three large traditional Chinese medicine (TCM) databases. 654 putative targets of LSYQ Decoction were predicted using a structure-based, reverse-docking algorithm online, of which 343 overlapped with BCa-related protein-coding genes. The protein-protein interaction (PPI) network was constructed to perform module analysis for further Gene Ontology (GO) annotations and Kyoto Encyclopedia Genes and Genomes (KEGG) pathway enrichment analysis, which identified CDK2, EGFR, MMP9 and PTGS2 as hub targets. The TCM-compound-target network and compound-target-pathway network together revealed that quercetin, diosmetin, enhydrin and luteolin were the main components of LSYQ Decoction. Finally, molecular docking showed the affinity between the key compounds and the hub target proteins to verify the accuracy of drug target prediction in the first place. The present study deciphered the core components and targets of LSYQ Decoction on the treatment of BCa in a comprehensive systemic pharmacological manner.
| S-EPMC9330057 | biostudies-literature
Project description:IntroductionNetwork pharmacology is in line with the holistic characteristics of TCM and can be used to elucidate the complex network of interactions between disease-specific genes and compounds in TCM herbal medicines. Here, we investigate the pharmacological mechanism of Xiaokui Jiedu decoction (XJD) for the treatment of ulcerative colitis (UC).MethodsThe Computational Systems Biology Laboratory Platform (TCMSP) database was searched and screened for the active ingredients of all drugs in XJD. The Uniport database was used to retrieve possible gene targets for the therapeutic effects of XJD. GeneCards, PharmGKB, TTD, and OMIM databases were used to retrieve XJD-related gene targets. A herb-compound-protein network and a protein-protein interaction (PPI) network were constructed, and hub genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to validate the interrelationship between disease target proteins and active drug components.ResultsA total of 135 XJD potential action targets, 5097 UC-related gene targets, and 103 XJD-UC intersection gene targets were screened. The hub gene targets of XJD that exert therapeutic effects on UC are RB1, MAPK1, TP53, JUN, NR3C1, MAPK3, and ESR1. GO enrichment analysis showed 741 biofunctional enrichments, and KEGG enrichment analysis showed 124 related pathway enrichments. Molecular docking showed that the active components of XJD (β-sitosterol, kaempferol, formononetin, quercetin, and luteolin) showed good binding activities to five of the six hub gene targets. Discussion. The active ingredients of XJD (β-sitosterol, kaempferol, formononetin, quercetin, and luteolin) may regulate the inflammatory and oxidative stress-related pathways of colon cells during the course of UC by binding to the hub gene targets. This may be a potential mechanism of XJD in the treatment of UC.
| S-EPMC8560263 | biostudies-literature
Project description:Gyejibokryeong-hwan (GBH) is a traditional formula comprised of five herbal medicines that is frequently used to treat blood stasis and related complex multifactorial disorders such as atherosclerosis. The present study used network pharmacology and molecular docking simulations to clarify the effect and mechanism of the components of GBH. Active compounds were selected using Oriental Medicine Advanced Searching Integrated System (OASIS) and the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and target genes linked to the selected components were retrieved using Search Tool for Interacting Chemicals (STITCH) and GeneCards. Functional analysis of potential target genes was performed through the Annotation, Visualization and Integrated Discovery (DAVID) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and molecular docking confirmed the correlation between five core compounds (quercetin, kaempferol, baicalein, ellagic acid, and baicalin) and six potential target genes (AKT1, CASP3, MAPK1, MAPK3, NOS2, and PTGS2). Molecular docking studies indicated that quercetin strongly interacted with six potential target proteins. Thus, these potential target proteins were closely related to TNF, HIF-1, FoxO, and PI3K-Akt signal pathways, suggesting that these factors and pathways may mediate the beneficial effects of GBH on atherosclerosis. Our results identify target genes and pathways that may mediate the clinical effects of the compounds contained within GBH on atherosclerosis.
| S-EPMC7764045 | biostudies-literature