Exploring the mechanism of Ginkgo biloba L. leaves in the treatment of vascular dementia based on network pharmacology, molecular docking, and molecular dynamics simulation.

Ginkgo biloba L. leaves (GBLs) play a substantial role in the treatment of vascular dementia (VD); however, the underlying mechanisms of action are unclear. This study was conducted to investigate the mechanisms of action of GBLs in the treatment of VD through network pharmacology, molecular docking, and molecular dynamics simulations. The active ingredients and related targets of GBLs were screened using the traditional Chinese medicine systems pharmacology, Swiss Target Prediction and GeneCards databases, and the VD-related targets were screened using the OMIM, DrugBank, GeneCards, and DisGeNET databases, and the potential targets were identified using a Venn diagram. We used Cytoscape 3.8.0 software and the STRING platform to construct traditional Chinese medicine-active ingredient-potential target and protein-protein interaction networks, respectively. After gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of potential targets using the DAVID platform, the binding affinity between key active ingredients and targets was analyzed by molecular docking, and finally, the top 3 proteins-ligand pairs with the best binding were simulated by molecular dynamics to verify the molecular docking results. A total of 27 active ingredients of GBLs were screened and 274 potential targets involved in the treatment of VD were identified. Quercetin, luteolin, kaempferol, and ginkgolide B were the core ingredients for treatment, and AKT1, TNF, IL6, VEGFA, IL1B, TP53, CASP3, SRC, EGFR, JUN, and EGFR were the main targets of action. The main biological processes involved apoptosis, inflammatory response, cell migration, lipopolysaccharide response, hypoxia response, and aging. PI3K/Akt appeared to be a key signaling pathway for GBLs in the treatment of VD. Molecular docking displayed strong binding affinity between the active ingredients and the targets. Molecular dynamics simulation results further verified the stability of their interactions. This study revealed the potential molecular mechanisms involved in the treatment of VD by GBLs using multi-ingredient, multi-target, and multi-pathway interactions, providing a theoretical basis for the clinical treatment and lead drug development of VD.

Pan J ，Tang J ，Gai J ，Jin Y ，Tang B ，Fan X ... -  《-》

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 ... -  《-》

Exploration of Ginkgo biloba leaves on non-small cell lung cancer based on network pharmacology and molecular docking.

Pharmacological studies have found Ginkgo biloba leaves have the effect of inhibiting neoplasms, it is clinically used in treating various neoplasms. However, the mechanism of Ginkgo biloba leaves in treating non-small cell lung cancer (NSCLC) remains unclear. The active components and corresponding targets of Ginkgo biloba leaves were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database, and the targets of NSCLC were obtained from the GeneCards, OMIM, TTD, and DrugBank databases. The common targets of NSCLC and Ginkgo biloba leaves were obtained from VENNY 2.1.0. The STRING database was utilized to construct protein-protein intersections, by using the Cytoscape 3.7.1 software, the protein-protein intersection was optimized and the drug-disease network diagram was constructed. The DAVID database was utilized to perform GO and KEGG analysis. Finally, The Autodock Vina software was used to perform molecular docking of core components and targets. The key components of Ginkgo biloba leaves in treating NSCLC include quercetin, luteolin, and kaempferol, which may act on Tp53, AKT1, and TNF. Bioinformatic annotation analysis results suggest that Ginkgo biloba leaves may implicated in PI3K-AKT and MAPK signaling pathways. The molecular docking results show the firm affinity between key ingredients and targets. The potential mechanism of Ginkgo biloba leaves in treating NSCLC has been discussed in this study, which provides a theoretical basis for the clinical treatment of NSCLC and further experimental validation.

Wang M ，Li R ，Bai M ，Zhou X ... -  《-》

Molecular targets and mechanisms of Guanxinning tablet in treating atherosclerosis: Network pharmacology and molecular docking analysis.

Guanxinning tablet (GXNT), a Chinese patent medicine, is composed of salvia miltiorrhiza bunge and ligusticum striatum DC, which may play the role of endothelial protection through many pathways. We aimed to explore the molecular mechanisms of GXNT against atherosclerosis (AS) through network pharmacology and molecular docking verification. The active ingredients and their potential targets of GXNT were obtained in traditional Chinese medicine systems pharmacology database and analysis platform and bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. DrugBank, TTD, DisGeNET, OMIM, and GeneCards databases were used to screen the targets of AS. The intersection targets gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis were performed in DAVID database. GXNT-AS protein-protein interaction network, ingredient-target network and herb-target-pathway network were constructed by Cytoscape. Finally, we used AutoDock for molecular docking. We screened 65 active ingredients of GXNT and 70 GXNT-AS intersection targets. The key targets of protein-protein interaction network were AKT1, JUN, STAT3, TNF, TP53, IL6, EGFR, MAPK14, RELA, and CASP3. The Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that pathways in cancer, lipid and atherosclerosis, and PI3K-Akt signaling pathway were the main pathways. The ingredient-target network showed that the key ingredients were luteolin, tanshinone IIA, myricanone, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone. The results of molecular docking showed that tanshinone IIA, dihydrotanshinlactone, dan-shexinkum d, 2-isopropyl-8-methylphenanthrene-3,4-dione, miltionone I, deoxyneocryptotanshinone, Isotanshinone II and 4-methylenemiltirone all had good binding interactions with AKT1, EGFR and MAPK14. The results of network pharmacology and molecular docking showed that the multiple ingredients within GXNT may confer protective effects on the vascular endothelium against AS through multitarget and multichannel mechanisms. AKT1, EGFR and MAPK14 were the core potential targets of GXNT against AS.

Niu C ，Zhang P ，Zhang L ，Lin D ，Lai H ，Xiao D ，Liu Y ，Zhuang R ，Li M ，Ma L ，Ye J ，Pan Y ... -  《-》

Study on Mechanism of Ginkgo biloba L. Leaves for the Treatment of Neurodegenerative Diseases Based on Network Pharmacology.

Wang J ，Chen X ，Bai W ，Wang Z ，Xiao W ，Zhu J ... -  《-》