Exploring the pharmacological components and effective mechanism of Mori Folium against periodontitis using network pharmacology and molecular docking.

To investigate the main active components, potential targets of action and analyze the potential molecular mechanisms of Mori Folium in preventing and treating periodontitis using network pharmacology and molecular docking methods. The main components and action targets of Mori Folium were obtained in TCMSP and ETCM databases, and then the action targets of Mori Folium components were inversing screening using Swiss Target Prediction and BATMAN-TCM databases. Targets associated with periodontitis were retrieved from OMIM, Genecard, DrugBank, NCBI Gene and DisGeNET databases. Intersectional targets of Mori Folium and periodontitis were obtained by Venn analysis. Construction of an "active components-targets" network to prevent and treat periodontitis in Mori Folium using Cytoscape 3.8.0. The STRING database was used to construct the protein-protein interaction (PPI) network of intersecting targets, and the core network was screened using CytoNCA and MCODE plug-ins. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the ClusterProfile package of R software, and then the "Mori Folium active components-targets-signaling pathway" network was constructed using Cytoscape software. Molecular docking was performed using AutoDock Vina software, and Pymol and LigPlus visualized the results. Sixteen active components and 1048 targets were screened from Mori Folium, of which 164 were intersectional with periodontitis targets and were considered potential therapeutic targets. The "Mori Folium active components-action targets" network identified Quercetin, Moracin D, Moracin E, Moracin G, Moracin H and Moracin B as the main active ingredients of Mori Folium for the prevention and treatment of periodontitis. PPI network analysis revealed interleukin 6 (IL6), albumin (ALB), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), RAC-alpha serine/threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), pro-epidermal growth factor (EGF), matrix metalloproteinase 9 (MMP9) and interleukin 6 (IL10) as the top 10 core potential targets. GO and KEGG enrichment analyses showed that the action targets of Mori Folium against periodontitis were mainly related to the response to bacterium and their lipopolysaccharide, angiogenesis and reactive oxygen species metabolic process, as well as through signaling pathways that regulate processes related to the accumulation of advanced glycation end products (AGEs), response to oxidative stress, response to inflammatory, and osteoclast differentiation during the development of the disease. Molecular docking revealed that Quercetin, Moracin D, Moracin E, Moracin G, Moracin H and Moracin B were able to bind stably to AKT1, PTGS2 and ESR1 targets, with Moracin E showing the most stable structure after binding to AKT1. In conclusion, this study revealed the active components, potential targets of action and the potential molecular mechanisms and pharmacological activities involved in the prevention and treatment of periodontitis in Mori Folium, providing a reference for the development of drugs from Mori Folium for the prevention and treatment of periodontitis.

Wu Z ，Ji X ，Shan C ，Song J ，Zhao J ... -  《-》

Exploring the Molecular Mechanism of Action of Yinchen Wuling Powder for the Treatment of Hyperlipidemia, Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Yinchen 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. The 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. A 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. This study is based on network pharmacology and reveals the potential molecular mechanisms involved in the treatment of hyperlipidemia by Yinchen Wuling powder.

Ye J ，Li L ，Hu Z 《-》

Exploring the mechanisms underlying the therapeutic effect of Salvia miltiorrhiza in diabetic nephropathy using network pharmacology and molecular docking.

The mechanisms underlying the therapeutic effect of Salvia miltiorrhiza (SM) on diabetic nephropathy (DN) were examined using a systematic network pharmacology approach and molecular docking. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of SM. Targets were obtained using the SwissTargetPrediction and TCMSP databases. Proteins related to DN were retrieved from the GeneCards and DisGeNET databases. A protein-protein interaction (PPI) network was constructed using common SM/DN targets in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The Metascape platform was used for Gene Ontology (GO) function analysis, and the Cytoscape plug-in ClueGO was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was performed using iGEMDOCK and AutoDock Vina software. Pymol and LigPlos were used for network mapping. Sixty-six active ingredients and 189 targets of SM were found. Sixty-four targets overlapped with DN-related proteins. The PPI network revealed that AKT serine/threonine kinase 1 (AKT1), VEGFA, interleukin 6 (IL6), TNF, mitogen-activated protein kinase 1 (MAPK1), tumor protein p53 (TP53), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 14 (MAPK14), and JUN were the ten most relevant targets. GO and KEGG analyses revealed that the common targets of DN and SM were mainly involved in advanced glycation end-products, oxidative stress, inflammatory response, and immune regulation. Molecular docking revealed that potential DN-related targets, including tumor necrosis factor (TNF), NOS2, and AKT1, more stably bound with salvianolic acid B than with tanshinone IIA. In conclusion, the present study revealed the active components and potential molecular therapeutic mechanisms of SM in DN and provides a reference for the wide application of SM in clinically managing DN.

Zhang L ，Han L ，Wang X ，Wei Y ，Zheng J ，Zhao L ，Tong X ... -  《-》

[Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment].

Ding WC ，Chen J ，Liao HY ，Feng J ，Wang J ，Zhang YH ，Ji XH ，Chen Q ，Wu XY ，Sun ZR ，Nie SN ... -  《-》

Research on the Regulatory Mechanism of Ginseng on the Tumor Microenvironment of Colorectal Cancer based on Network Pharmacology and Bioinformatics Validation.

A network pharmacology study on the biological action of ginseng in the treatment of colorectal cancer (CRC) by regulating the tumor microenvironment (TME). To investigate the potential mechanism of action of ginseng in the treatment of CRC by regulating TME. This research employed network pharmacology, molecular docking techniques, and bioinformatics validation. Firstly, the active ingredients and the corresponding targets of ginseng were retrieved using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Traditional Chinese Medicine Integrated Database (TCMID), and the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan). Secondly, the targets related to CRC were retrieved using Genecards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM). Tertiary, the targets related to TME were derived from screening the GeneCards and National Center for Biotechnology Information (NCBI)-Gene. Then the common targets of ginseng, CRC, and TME were obtained by Venn diagram. Afterward, the Protein-protein interaction (PPI) network was constructed in the STRING 11.5 database, intersecting targets identified by PPI analysis were introduced into Cytoscape 3.8.2 software cytoHubba plugin, and the final determination of core targets was based on degree value. The OmicShare Tools platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets. Autodock and PyMOL were used for molecular docking verification and visual data analysis of docking results. Finally, we verified the core targets by Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases in bioinformatics. A total of 22 active ingredients and 202 targets were identified to be closely related to the TME of CRC. PPI network mapping identified SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 as possible core targets. Go enrichment analysis showed that it was mainly involved in T cell co-stimulation, lymphocyte co-stimulation, growth hormone response, protein input, and other biological processes; KEGG pathway analysis found 123 related signal pathways, including EGFR tyrosine kinase inhibitor resistance, chemokine signaling pathway, VEGF signaling pathway, ErbB signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, etc. The molecular docking results showed that the main chemical components of ginseng have a stable binding activity to the core targets. The results of the GEPIA database showed that the mRNA levels of PIK3R1 were significantly lowly expressed and HSP90AA1 was significantly highly expressed in CRC tissues. Analysis of the relationship between core target mRNA levels and the pathological stage of CRC showed that the levels of SRC changed significantly with the pathological stage. The HPA database results showed that the expression levels of SRC were increased in CRC tissues, while the expression of STAT3, PIK3R1, HSP90AA1, and AKT1 were decreased in CRC tissues. Ginseng may act on SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 to regulate T cell costimulation, lymphocyte costimulation, growth hormone response, protein input as a molecular mechanism regulating TME for CRC. It reflects the multi-target and multi-pathway role of ginseng in modulating TME for CRC, which provides new ideas to further reveal its pharmacological basis, mechanism of action and new drug design and development.

Wang T ，Zhang W ，Fang C ，Wang N ，Zhuang Y ，Gao S ... -  《-》