Exploring the mechanism of Xiaoqinglong decoction in the treatment of infantile asthma based on network pharmacology and molecular docking.

To explore the mechanism of Xiaoqinglong decoction (XQLD) in the treatment of infantile asthma (IA) based on network pharmacology and molecular docking. The active ingredients of fdrugs in XQLD were retrieved from Traditional Chinese Medicine Systems Pharmacology database and then the targets of drug ingredients were screened. The disease targets of IA were obtained from OMIM and Gencards databases, and the intersection targets of XQLD in the treatment of IA were obtained by Venny 2.1 mapping of ingredient targets and disease targets. Cytoscape software was used to construct active ingredient-intersection target network. The potential targets of XQLD in the treatment of IA were analyzed by protein-protein interaction network using STRING platform, and the Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were obtained by R Studio software. AutoDock was used to perform molecular docking for verification. In this study, 150 active ingredients of XQLD were obtained, including quercetin, kaempferol, β-sitosterol, luteolin, stigmasterol, and so on. And 92 intersection targets of drugs and diseases were obtained, including interleukin 6 (IL6), cystatin 3, estrogen receptor 1, hypoxia inducible factor 1A, HSP90AA1, epidermal growth factor receptor and so on. There were 127 items of Gene Ontology enrichment analysis and 125 Kyoto Encyclopedia of Genes and Genomes enrichment results, showing that apoptosis, IL-17 signaling pathway, tumor necrosis factor signaling pathway, P13K-Akt signaling pathway and other pathways may play a key role in the treatment of IA by XQLD. The results of molecular docking showed that the key active ingredients including quercetin, kaempferol, β-sitosterol, luteolin, stigmasterol, and the core targets including IL6, cystatin 3, estrogen receptor 1, hypoxia inducible factor 1A, HSP90AA1, and epidermal growth factor receptor had good binding activity. Through network pharmacology and molecular docking, the potential targets and modern biological mechanisms of XQLD in the treatment of IA were preliminarily revealed in the study, which will provide reference for subsequent animal experiments and clinical trials.

Chen D ，Chen Q ，Zhao K ，Guo Y ，Huang Y ，Yuan Z ，Cai Y ，Li S ，Xu J ，Lin X ... -  《-》

Therapeutic Mechanism of Xiaoqinglong Decoction against COVID-19 Based on Network Pharmacology and Molecular Docking Technology.

A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear. In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19. Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking. We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins. This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.

Li HL ，Zhou JP ，Deng JM 《-》

Potential Molecular Mechanisms of Ephedra Herb in the Treatment of Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking.

To explore the possible mechanisms of Ephedra herb (EH) in the treatment of nephrotic syndrome (NS) by using network pharmacology and molecular docking in this study. Active ingredients and related targets of EH were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the gene names corresponding to the proteins were found through the UniProt database. Then, target genes related to NS were screened out from GeneCards, PharmGKB, and OMIM databases. Next, the intersection targets were obtained successfully through Venn diagram, which were also seen as key target genes of EH and NS. Cytoscape 3.9.0 software was used to construct the effective "active ingredient-target" network diagram, and "drug-ingredient-target-disease (D-I-T-D)" network diagram. After that, the STRING database was used to construct a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment involved in the targets were performed by the DAVID database and ClueGO plugin in Cytoscape. Finally, AutoDockTools software was used for molecular docking to verify the binding strength between main active ingredients and key target proteins. A total of 22 main active ingredients such as quercetin, kaempferol, luteolin, and naringenin were obtained, which could act on 105 targets related to NS. Through PPI network, 53 core targets such as AKT1, TNF, IL6, VEGFA, and IL1B were found, which might play a crucial role in the treatment of NS. Meanwhile, these targets were significantly involved in PI3K-Akt signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway, hepatitis B, and pathways in cancer through GO and KEGG enrichment analysis. The docking results indicated that active ingredients such as kaempferol, luteolin, quercetin, and naringenin all had good binding to the target protein AKT1 or TNF. Among them, luteolin and naringenin binding with AKT1 showed the best binding energy (-6.2 kcal/mol). This study indicated that the potential mechanism of EH in treating NS may be related to PI3K-Akt signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway, which provided better approaches for exploring the mechanism in treating NS and new ideas for further in vivo and in vitro experimental verifications.

Yao T ，Wang Q ，Han S ，Lu Y ，Xu Y ，Wang Y ... -  《-》

Investigation of the mechanism of Prunella vulgaris in treatment of papillary thyroid carcinoma based on network pharmacology integrated molecular docking and experimental verification.

To analyze the molecular mechanism of Prunella vulgaris L. (PV) in the treatment of papillary thyroid carcinoma (PTC) by using network pharmacology combined with molecular docking verification. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to predict the main active components of PV, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, PubChem, and Swiss Target Prediction databases were used to obtain the corresponding targets of all active components. Targets collected for PTC treatment through Gene Cards, Digest and Online Mendelian Inheritance in Man databases respectively. The Search Tool for the Retrieval of Interaction Gene/Protein database was used to obtain the interaction information between proteins, and the topology analysis and visualization were carried out through Cytoscape 3.7.2 software (https://cytoscape.org/). The R package cluster profiler was used for gene ontology and Kyoto encyclopedia of genes and genomes analysis. The "active ingredient-target-disease" network was constructed by using Cyto scape 3.7.2, and topological analysis was carried out to obtain the core compound. The molecular docking was processed by using Discovery Studio 2019 software, and the core target and active ingredient were verified. The inhibition rate was detected by CCK8 method. Western blot was used to detect the expression levels of kaempferol anti-PTC related pathway proteins. A total of 11 components and 83 corresponding targets in the component target network of PV, of which 6 were the core targets of PV in the treatment of PTC. It was showed that quercetin, luteolin, beta (β)-sitosterol, kaempferol may be the core components of PV in the treatment of PTC. vascular endothelial growth factor A, tumor protein p53, transcription factor AP-1, prostaglandin endoperoxidase 2, interleukin 6, and IL-1B may be important targets for the treatment of PTC. The main biological processes mainly including response to nutrient levels, response to xenobiotic stimulus, response to extracellular stimulus, external side of plasma membrane, membrane raft, membrane microdomain, serine hydrolase activity, serine-type endopeptidase activity, antioxidant activity, etc IL-17 signaling pathway, and PI3K-Akt signaling pathway may affect the recurrence and metastasis of PTC. Kaempferol may significantly reduce the activity of Papillary cells of human thyroid carcinoma bcpap cell lines cells compared with quercetin, luteolin, β-sitosterol. Kaempferol may reduce the protein expression levels of interleukin 6, vascular endothelial growth factor A, transcription factor AP-1, tumor protein p53, 1L-1B and prostaglandin endoperoxidase 2, respectively. PV has the characteristics of multi-components, multi-targets and multi- pathways in the treatment of PTC, which network pharmacology help to provides a theoretical basis for the screening of effective components of PV and further research.

Zhu X ，Li Y ，Wang X ，Huang Y ，Mao J ... -  《-》

Network pharmacology to explore the molecular mechanisms of Prunella vulgaris for treating thyroid cancer.

Thyroid cancer (TC) is the most common endocrine malignancy that has rapidly increased in global incidence. Prunella vulgaris (PV) has manifested therapeutic effects in patients with TC. We aimed to investigate its molecular mechanisms against TC and provide potential drug targets by using network pharmacology and molecular docking. The ingredients of PV were retrieved from Traditional Chinese Medicine Systematic Pharmacology Database. TC-related gene sets were established using the GeneCard and OMIM databases. The establishment of the TC-PV target gene interaction network was accomplished using the STRING database. Cytoscape constructed networks for visualization. Protein-protein interaction, gene ontology and the biological pathway Kyoto encyclopedia of genes and genomes enrichment analyses were performed to discover the potential mechanism. Molecular docking technology was used to analyze the effective compounds from PV for treating TC. 11 active compounds and 192 target genes were screened from PV. 177 potential targets were obtained by intersecting PV and TC gene sets. Network pharmacological analysis showed that the PV active ingredients including Vulgaxanthin-I, quercetin, Morin, Stigmasterol, poriferasterol monoglucoside, Spinasterol, kaempferol, delphinidin, stigmast-7-enol, beta-sitosterol and luteolin showed better correlation with TC target genes such as JUN, AKT1, mitogen-activated protein kinase 1, IL-6 and RELA. The gene ontology and Kyoto encyclopedia of genes and genomes indicated that PV can act by regulating the host defense and response to oxidative stress immune response and several signaling pathways are closely associated with TC, such as the TNF and IL-17. Protein-protein interaction network identified 8 hub genes. The molecular docking was conducted on the most significant gene MYC. Eleven active compounds of PV can enter the active pocket of MYC, namely poriferasterol monoglucoside, stigmasterol, beta-sitosterol, vulgaxanthin-I, spinasterol, stigmast-7-enol, luteolin, delphinidin, morin, quercetin and kaempferol. Further analysis showed that oriferasterol monoglucoside, followed by tigmasterol, were the potential therapeutic compound identified in PV for the treatment of TC. The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of PV. MYC is a promising drug target to reduce oxidative stress damage and potential anti-tumor effect. Oriferasterol monoglucoside and kaempferol were 2 bioactive compounds of PV to treat TC. This provides a basis to understand the mechanism of the anti-TC activity of PV.

Zhang Z ，Zhou J ，Guo R ，Zhou Q ，Wang L ，Xiang X ，Ge S ，Cui Z ... -  《-》