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 ... -  《-》

Exploring the mechanism of bioactive components of Prunella vulgaris L. in treating hepatocellular carcinoma based on network pharmacology.

Tu H ，Feng Y ，Wang W ，Zhou H ，Cai Q ，Feng Y ... -  《-》

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 ... -  《-》

Anti-papillary thyroid carcinoma effects of dioscorea bulbifera L. through ferroptosis and the PI3K/AKT pathway based on network pharmacology and experimental validation.

Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer with a rising global incidence. Despite favorable prognoses, a significant recurrence rate persists. Dioscorea bulbifera L. (DBL), a traditional Chinese medicine, has been historically used for thyroid-related disorders. However, its therapeutic effects and mechanisms of action on PTC remain unclear. To explore the potential therapeutic effects, principal active components, and molecular mechanisms of DBL in the treatment of PTC through network pharmacology and molecular docking, with experimental validation conducted to corroborate these findings. The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was utilized as a systematic tool for collecting and screening the phytochemical components of DBL, and for establishing associations between these components and molecular targets. Based on this, network data was visually processed using Cytoscape software (version 3.8.0). Concurrently, precise molecular docking studies of the principal active components of DBL and their corresponding targets were conducted using Autodock software. Additionally, PTC-related genes were selected through the GeneCards and GEO databases. We further employed the DAVID bioinformatics resources to conduct comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the intersecting genes between DBL and PTC. These analyses aid in predicting the potential therapeutic actions of DBL on PTC and its mechanisms of action. To validate these findings, corresponding in vitro experimental studies were also conducted. In this investigation, 14 bioactive compounds of DBL and 195 corresponding molecular targets were identified, with 127 common targets shared between DBL and PTC. Molecular docking revealed strong binding affinities between major bioactive compounds and target proteins. GO enrichment analysis unveiled key processes involved in DBL's action. KEGG analysis highlighted DBL's modulation of the PI3K/AKT signaling pathway. Experimental outcomes demonstrated DBL's potential in inhibiting PTC cell proliferation and migration, suppressing PI3K/AKT pathway activation, and promoting ferroptosis. In conclusion, DBL offers a multifaceted therapeutic approach for PTC, targeting multiple molecular entities and influencing diverse biological pathways. Network pharmacology and molecular docking shed light on DBL's potential utility in PTC treatment, substantiated by experimental validation. This study contributes valuable insights into using DBL as a promising therapeutic agent for PTC management.

Gao Y ，Yang Z ，Ji T ，Zhou P ，Geng L ，Gao X ... -  《-》