Exploring the treatment of COVID-19 with Yinqiao powder based on network pharmacology.
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ABSTRACT:
SUBMITTER: Lin H
PROVIDER: S-EPMC8013442 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:MethodsMetabolomics was used to detect the secondary metabolites in SLBZP; the target protein was acquired by target fishing according to the compound's structure. The SymMap database was used to search herbal medicines for the target protein. The target gene of IBS gave rise to the common gene protein which is the potential target of SLBZP in IBS therapy. The interactions between target proteins were analyzed in a STRING database, the protein relationship network was analyzed using Cytoscape software, and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the core target gene group was carried out in a DAVID database in order to construct the "compound-traditional Chinese medicine/molecule-target-pathway" network. Molecular docking was used to verify the core protein and its related small molecular compounds.ResultThere were 129 types of secondary metabolites in SLBZP. 80 target proteins of these metabolites were potential core targets for IBS treatment including acetylcholinesterase (AChE), arachidonate-5-lipoxygenase (ALOX5), B-cell lymphoma-2 (BCL2), recombinant cyclin D1 (CCND1), and catenin-β1 (CTNNB1), among others. Results from these targets indicated that the most enriched pathway was the tumor necrosis factor (TNF) signaling pathway (p < 0.001) and that the most abundant pathway was signal transduction. In the network nodes of the TNF signaling pathway, the Chinese medicines with the highest aggregation were Lablab semen album and Glycyrrhizae radix et rhizoma (degree = 11). The small molecules with the highest aggregation were oxypeucedanin and 3,5,6,7,8,3',4'-heptamethoxyflavone (degree = 4). Molecular docking results confirmed that daidzein 7-O-glucoside (daidzin) had the highest degree of binding to TNF proteins in the TNF signaling pathway.ConclusionThis study shows that SLBZP can treat IBS by influencing multiple targets and pathways, of which the TNF signaling pathway may be the most significant. This typifies the pharmacological characteristics of traditional Chinese medicine, i.e., multiple targets, numerous pathways, and specific therapeutic effects on diseases. SLBZP can therefore be used as a candidate drug for clinical IBS by intervening in human signal transduction.
| S-EPMC8632384 | biostudies-literature
Project description:BackgroundCOVID-19 has caused a global pandemic, and there is no wonder drug for epidemic control at present. However, many clinical practices have shown that traditional Chinese medicine has played an important role in treating the outbreak. Among them, ephedra-bitter almond is a common couplet medicine in anti-COVID-19 prescriptions. This study aims to conduct an exploration of key components and mechanisms of ephedra-bitter almond anti-COVID-19 based on network pharmacology.Material and methodsWe collected and screened potential active components of ephedra-bitter almond based on the TCMSP Database, and we predicted targets of the components. Meanwhile, we collected relevant targets of COVID-19 through the GeneCards and CTD databases. Then, the potential targets of ephedra-bitter almond against COVID-19 were screened out. The key components, targets, biological processes, and pathways of ephedra-bitter almond anti-COVID-19 were predicted by constructing the relationship network of herb-component-target (H-C-T), protein-protein interaction (PPI), and functional enrichment. Finally, the key components and targets were docked by AutoDock Vina to explore their binding mode.ResultsEphedra-bitter almond played an overall regulatory role in anti-COVID-19 via the patterns of multi-component-target-pathway. In addition, some key components of ephedra-bitter almond, such as β-sitosterol, estrone, and stigmasterol, had high binding activity to 3CL and ACE2 by molecular docking simulation, which provided new molecular structures for new drug development of COVID-19.ConclusionEphedra-bitter almonds were used to prevent and treat COVID-19 through directly inhibiting the virus, regulating immune responses, and promoting body repair. However, this work is a prospective study based on data mining, and the findings need to be interpreted with caution.
| S-EPMC7653455 | biostudies-literature
Project description:Since coronavirus disease 2019 (COVID-19) is a serious new worldwide public health crisis with significant morbidity and mortality, effective therapeutic treatments are urgently needed. Drug repurposing is an efficient and cost-effective strategy with minimum risk for identifying novel potential treatment options by repositioning therapies that were previously approved for other clinical outcomes. Here, we used an integrated network-based pharmacologic and transcriptomic approach to screen drug candidates novel for COVID-19 treatment. Network-based proximity scores were calculated to identify the drug-disease pharmacological effect between drug-target relationship modules and COVID-19 related genes. Gene set enrichment analysis (GSEA) was then performed to determine whether drug candidates influence the expression of COVID-19 related genes and examine the sensitivity of the repurposing drug treatment to peripheral immune cell types. Moreover, we used the complementary exposure model to recommend potential synergistic drug combinations. We identified 18 individual drug candidates including nicardipine, orantinib, tipifarnib and promethazine which have not previously been proposed as possible treatments for COVID-19. Additionally, 30 synergistic drug pairs were ultimately recommended including fostamatinib plus tretinoin and orantinib plus valproic acid. Differential expression genes of most repurposing drugs were enriched significantly in B cells. The findings may potentially accelerate the discovery and establishment of an effective therapeutic treatment plan for COVID-19 patients.
| S-EPMC8069812 | biostudies-literature
Project description:Nonalcoholic steatohepatitis (NASH), a progression of nonalcoholic fatty liver disease (NAFLD), is a clinical syndrome characterized by liver steatosis, inflammation, and hepatocellular damage. Ganlu powder (GLP) is a classic traditional Chinese medicine prescription that has shown favorable treatment effects on NASH. However, the underlying therapeutic mechanisms are still poorly understood. This study is aimed at exploring the potential mechanism of GLP in the treatment of NASH via network pharmacology and molecular docking. PubMed and CNKI databases were used to identify the components of GLP. Swiss and STITCH databases were employed to obtain corresponding drug targets. NASH targets were adopted from the Therapeutic Target Database (TTD), DisGeNET, DrugBank, GeneCards, and MalaCards databases. Cytoscape software was utilized to construct "drug-ingredient-target-disease" networks and the protein-protein interaction (PPI) network of GLP in NASH. AKT1 was identified as the key target. The GO functional enrichment analysis revealed that GLP might treat NASH by modulating the inflammatory response and regulating phosphatidylinositol 3-kinase signaling. The KEGG analysis showed that GLP might treat NASH by regulating the tumor necrosis factor (TNF) signal pathway by affecting the role of AKT1. According to the network pharmacology results, a virtual docking of active compounds with AKT1 was carried out, and the results indicated that the 7 components, berberine, epiberberine, jatrorrhizine, coptisine, palmatine, evodiamine, and rutecarpine, can bind stably with AKT1 and have higher binding energy than AKT1 inhibitors. The overall study findings suggest that GLP may treat NASH by regulating AKT1.
| S-EPMC9259220 | biostudies-literature
Project description:ObjectiveUlcerative colitis is an intestinal condition that severely affects the life quality of a patient. Jiawei Zhengqi powder (JWZQS) has some therapeutic benefits for ulcerative colitis. The current study investigated the therapeutic mechanism of JWZQS for ulcerative colitis using a network pharmacology analytical approach.MethodsIn this study, network pharmacology was used to investigate the potential mechanism of JWZQS in treating ulcerative colitis. The common targets between the two were identified, and a network map was created with the Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of JWZQS was performed using the Metascape database. Protein-protein interaction networks (PPI) was created to screen core targets and main components, and molecular docking was conducted between the main components and core targets. The expression levels of IL-1β, IL-6, and TNF-α were detected in animal experiments. Their effect on the NF-κB signaling pathway and the protective mechanism of JWZQS on the colon by tight junction protein were investigated.ResultsThere were 2127 potential ulcerative colitis targets and 35 components identified, including 201 non-reproducible targets and 123 targets shared by drugs and diseases. Following the analysis, we discovered 13 significant active components and 10 core targets. The first 5 active ingredients and their corresponding targets were molecularly docked, and the results showed a high level of affinity. GO analysis showed that JWZQS participate in multiple biological processes to treat UC. KEGG analysis showed that JWZQS may be involved in regulating multiple pathways, and the NF-κB signaling pathway was selected for analysis and verification. JWZQS has been shown in animal studies to effectively inhibit the NF-κB pathway; reduce the expression of IL-1β, TNF-α, and IL-6 in colon tissue; and increase the expression of ZO-1, Occludin, and Claudin-1.ConclusionThe network pharmacological study provides preliminary evidence that JWZQS can treat UC through multiple components and targets. JWZQS has been shown in animal studies to effectively reduce the expression levels of IL-1β, TNF-α, and IL-6, inhibit the phosphorylation of the NF-κB pathway, and alleviate colon injury. JWZQS can be used in clinical, but the precise mechanism of UC treatment requires further investigation.
| S-EPMC9970719 | biostudies-literature
Project description:BackgroundChinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach.MethodsTCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a "drug-active ingredient-potential target" network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape.ResultsA total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of "drug-component-target-biological process-signaling pathway". Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway.ConclusionsOur study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.
| S-EPMC7512049 | biostudies-literature
Project description:BackgroundBreast cancer is the most common malignancy among women worldwide, but the long-term endocrine therapy is frequently associated with adverse side effects. Danzhi Xiaoyao powder (DXP) is a herbal formula that has an effect on breast cancer, especially ER-positive breast cancer. However, the active compounds, potential targets, and pharmacological and molecular mechanism of its action against cancer remain unclear.MethodsA network pharmacology approach comprising drug-likeness evaluation, oral bioavailability prediction, Caco-2 permeability prediction, multiple compound target prediction, multiple known target collection, breast cancer genes collection, and network analysis has been used in this study.ResultsFour networks are set up-namely, ER-positive breast cancer network, compound-compound target network of DXP, DXP-ER-positive breast cancer network, and compound-known target-ER-positive breast cancer network. Some ER-positive breast cancer and DXP related targets, clusters, biological processes, and pathways, and several potential anticancer compounds are found.ConclusionThis network analysis successfully predicted, illuminated, and confirmed the molecular synergy of DXP for ER-positive breast cancer, got potential anticancer active compounds, and found the potential ER-positive breast cancer associated targets, cluster, biological processes, and pathways. This work also provides clues to the researcher who explores ethnopharmacological or/and herbal medicine's or even multidrugs' various synergies.
| S-EPMC5859839 | biostudies-literature
Project description:BackgroundYinchen Wuling powder is often used to treat clinical hyperlipidemia, although its mechanism of action remains unclear. In this study, we aimed to investigate the active ingredients found in Yinchen Wuling powder and find its mechanism of action when treating hyperlipidemia, using a combination of network pharmacology, molecular docking, and molecular dynamics simulation approaches.MethodsThe TCMSP database was used to obtain the principle active ingredients found in Yinchen Wuling powder and the NCBI and DisGeNet databases were used to obtain the main target genes involved in hyperlipidemia, and the intersectional targets were obtained by EXCEL. We also used Cytoscape 3.7.2 software to construct a "Traditional Chinese Medicine-Active Ingredient-Target" network and use STRING platform to conduct "protein-protein interactional" (PPI) analyses on the intersection targets. Bioconductor software and RX 64 4.0.0 software were then used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the targets. Molecular docking of core protein-ligand interactions was modeled using AutoDock Vina software. A simulation of molecular dynamics was conducted for the optimal core protein-ligand obtained by molecular docking using Amber18 software.ResultsA total of 63 active ingredients were found in Yinchen Wuling powder, corresponding to 175 targets, 508 hyperlipidemia targets, and 55 intersection targets in total. Cytoscape 3.7.2 showed that the key active ingredients were quercetin, isorhamnetin, taxifolin, demethoxycapillarisin, and artepillin A. The PPI network showed that the key proteins involved were AKT1, IL6, VEGFA, and PTGS2. GO enrichment analysis found that genes were enriched primarily in response to oxygen levels and nutrient levels of the vesicular lumen and were associated with membrane rafts. These were mainly enriched in AGE-RAGE (advanced glycation end products-receptor for advanced glycation end products) signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis, as well as other pathways. The molecular docking results indicated key binding activity between PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin. Results from molecular dynamics simulations showed that PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin bound more stably, and their binding free energies were PTGS2-quercetin -29.5 kcal/mol, PTGS2-isorhamnetin -32 kcal/mol, and PTGS2-taxifolin -32.9 kcal/mol.ConclusionThis study is based on network pharmacology and reveals the potential molecular mechanisms involved in the treatment of hyperlipidemia by Yinchen Wuling powder.
| S-EPMC8568510 | biostudies-literature
Project description:BackgroundChinese medicine Xuebijing (XBJ) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases. But the bioactive compounds and potential mechanisms of XBJ for COVID-19 prevention and treatment are unclear. This study aimed to examine the potential effector mechanisms of XBJ on COVID-19 based on network pharmacology.MethodsWe searched Chinese and international papers to obtain the active ingredients of XBJ. Then, we compiled COVID-19 disease targets from the GeneCards gene database and via literature searches. Next, we used the SwissTargetPrediction database to predict XBJ's effector targets and map them to the abovementioned COVID-19 disease targets in order to obtain potential therapeutic targets of XBJ. Cytoscape software version 3.7.0 was used to construct a "XBJ active-compound-potential-effector target" network and protein-protein interaction (PPI) network, and then to carry out network topology analysis of potential targets. We used the ClueGO and CluePedia plugins in Cytoscape to conduct gene ontology (GO) biological process (BP) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of XBJ's effector targets. We used AutoDock vina and PyMOL software for molecular docking.ResultsWe obtained 144 potential COVID-19 effector targets of XBJ. Fourteen of these targets-glyceraldehyde 3-phosphate dehydrogenase (GAPDH), albumin (ALB), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), Caspase-3 (CASP3), signal transducer and activator of transcription 3 (STAT3), MAPK8, prostaglandin-endoperoxide synthase 2 (PTGS2), JUN, interleukin-2 (IL-2), estrogen receptor 1 (ESR1), and MAPK14 had degree values > 40 and therefore could be considered key targets. They participated in extracellular signal-regulated kinase 1 and 2 (ERK1, ERK2) cascade, the T-cell receptor signaling pathway, activation of MAPK activity, cellular response to lipopolysaccharide, and other inflammation- and immune-related BPs. XBJ exerted its therapeutic effects through the renin-angiotensin system (RAS), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), MAPK, phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt)-vascular endothelial growth factor (VEGF), toll-like receptor (TLR), TNF, and inflammatory-mediator regulation of transient receptor potential (TRP) signaling pathways to ultimately construct a "drug-ingredient-target-pathway" effector network. The molecular docking results showed that the core 18 effective ingredients had a docking score of less than - 4.0 with those top 10 targets.ConclusionThe active ingredients of XBJ regulated different genes, acted on different pathways, and synergistically produced anti-inflammatory and immune-regulatory effects, which fully demonstrated the synergistic effects of different components on multiple targets and pathways. Our study demonstrated that key ingredients and their targets have potential binding activity, the existing studies on the pharmacological mechanisms of XBJ in the treatment of sepsis and severe pneumonia, could explain the effector mechanism of XBJ in COVID-19 treatment, and those provided a preliminary examination of the potential effector mechanism in this disease.
| S-EPMC7563914 | biostudies-literature
Project description:Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.
| S-EPMC7808608 | biostudies-literature