Prediction of network pharmacology and molecular docking-based strategy to determine potential pharmacological mechanism of Liuwei Dihuang pill against tinnitus.

Liuwei Dihuang Pill is widely used to treat tinnitus in China. However, the underlying mechanism of Liuwei Dihuang Pill in treating tinnitus still remains unclear. To explore the potential pharmacological mechanism of Liuwei Dihuang Pill in the treatment of tinnitus based on network pharmacology and molecular docking. The active components of the Liuwei Dihuang Pill were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database. Cytoscape software was used to draw the active component-target network diagram of Liuwei Dihuang Pill, and obtain the core components. Then the corresponding targets were also obtained from the TCMSP database. Targets related to tinnitus were obtained from the GeneCards, DisGeNET, TTD and DrugBank databases. The String database was used to construct protein-protein interaction (PPI) network of common targets of drugs and diseases, then the core targets were screened out. The Annotation, Visualization and Integrated Discovery (DAVID) database was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of common targets. Finally, the molecular docking between the core component and the core target was carried out by AutoDock. The core components of Liuwei Dihuang Pill in the treatment of tinnitus including quercetin, stigmasterol, kaempferol, β-sitosterol, tetrahydroalstonine, which may act on core targets such as STAT3, transcription factor AP-1 (JUN), tumor necrosis factor (TNF), interleukin-6 and MAPK3. HIF-1 signaling pathway, Influenza A, P53 signaling pathway, and Toll-like receptor signaling pathway play a role in anti-inflammatory, improving microcirculation in the blood-labyrinth barrier, increasing cochlear blood flow, and preventing hair cell damage. The molecular docking results showed that the affinity between core components and core targets was good. The potential mechanism of Liuwei Dihuang Pill in the treatment of tinnitus was preliminarily discussed in this study, which may provide a theoretical basis and evidence for further experimental research.

Wu Z ，Zhu Z ，Cao J ，Wu W ，Hu S ，Deng C ，Xie Q ，Huang X ，You C ... -  《-》

A network pharmacological-based study of the mechanism of Liuwei Dihuang pill in the treatment of chronic kidney disease.

Chronic kidney disease (CKD) is a progressive disease that poses a huge economic burden to society. Liuwei Dihuanng pill is an effective treatment for chronic kidney disease, but its treatment mechanism is unclear. The rapid development of network pharmacology has provided new strategies for studying Chinese medicine. The traditional Chinese medicine systems pharmacology database and analysis platform was used to obtain the bioactive components and targets of Liuwei Dihuanng pill. The sources for the CKD-related targets were then obtained from the Genecards, OMIM, TTD, and DisGeNET databases. R was used to identify the intersecting genes for Liuwei Dihuang pill and CKD-related targets. Analysis of protein-protein interactions (PPI) was performed using STRING, and PPI networks and drug-component-target networks were constructed using Cytoscape software. Kyoto encyclopedia of genes and genomes pathway and gene ontology enrichment analyses were performed using R. Finally, molecular docking was performed to determine the binding activity between bioactive components and the targets. After screening and data de-duplication of 74 active components, 209 drug targets, and 14,794 disease targets, a total of 204 drug-disease targets were acquired. Subsequently, a drug-component-target network and PPI network were established. The primary components of Liuwei Dihuang pill included quercetin, stigmasterol, kaempferol, beta-sitosterol, tetrahydroalstonine, kadsurenone, hederagenin, hancinone C, diosgenin, and sitosterol. In addition, JUN, AKT1, TP53, RELA, MAPK1, FOS, TNF, IL6, ESR1, and RXRA were identified as the main targets. Gene ontology function enrichment analysis revealed that these targets were involved in reactive oxygen species metabolic processes, responses to metal ions and to chemical stimuli, G protein-coupled amine receptor activity, and nuclear factor receptor activity. Kyoto encyclopedia of genes and genomes enrichment analysis showed that these targets were involved in the AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on. Molecular docking results indicated good binding activity between the core targets and core components. The potential mechanism of Liuwei Dihuanng pill in the treatment of CKD was preliminarily discussed in this study, providing a theoretical basis and evidence for further experimental research.

Xie X ，Lou H ，Shi Y ，Gan G ，Deng H ，Ma X ，Meng M ，Gao X ... -  《-》

Study on the Mechanism of Liuwei Dihuang Pills in Treating Parkinson's Disease Based on Network Pharmacology.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Liuwei Dihuang (LWDH) pills have a good effect on PD, but its mechanism remains unclear. Network pharmacology is the result of integrating basic theories and research methods of medicine, biology, computer science, bioinformatics, and other disciplines, which can systematically and comprehensively reflect the mechanism of drug intervention in disease networks. The main components and targets of herbs in LWDH pills were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Its active components were screened based on absorption, distribution, metabolism, and excretion (ADME); the PD-related targets were obtained from the Genecards, OMIM, TTD, and DRUGBANK databases. We used R to take the intersection of LWDH- and PD-related targets and Cytoscape software to construct the drug-component-target network. Moreover, STRING and Cytoscape software was used to analyze protein-protein interactions (PPI), construct a PPI network, and explore potential protein functional modules in the network. The Metascape platform was used to perform KEGG pathway and GO function enrichment analyses. Finally, molecular docking was performed to verify whether the compound and target have good binding activity. After screening and deduplication, 210 effective active ingredients, 204 drug targets, 4333 disease targets, and 162 drug-disease targets were obtained. We consequently constructed a drug-component-targets network and a PPI-drug-disease-targets network. The results showed that the hub components of LWDH pills were quercetin, stigmasterol, kaempferol, and beta-sitosterol; the hub targets were AKT1, VEGFA, and IL6. GO and KEGG enrichment analyses showed that these targets are involved in neuronal death, G protein-coupled amine receptor activity, reactive oxygen species metabolic processes, membrane rafts, MAPK signaling pathways, cellular senescence, and other biological processes. Molecular docking showed that the hub components were in good agreement with the hub targets. LWDH pills have implications for the treatment of PD since they contain several active components, target multiple ligands, and activate various pathways. The hub components possibly include quercetin, stigmasterol, kaempferol, and beta-sitosterol and act through pairing with hub targets, such as AKT1, VEGFA, and IL6, to regulate neuronal death, G protein-coupled amine receptor activity, reactive oxygen species metabolic process, membrane raft, MAPK signaling pathway, and cellular senescence for the treatment of PD.

Lin D ，Zeng Y ，Tang D ，Cai Y ... -  《-》

Network pharmacology and experimental validation to explore the role and potential mechanism of Liuwei Dihuang Decoction in prostate cancer.

To evaluate the anti-tumor effector of Liuwei Dihuang Decoction (LWDHD) in prostate cancer (PCa) and explore the potential mechanism using experimental validation, network pharmacology, bioinformatics analysis, and molecular docking. CCK test, Clone formation assay and wound-healing assays were used to determine the effect of LWDHD on prostate cancer growth and metastasis. The active ingredients and targets of LWDHD were obtained from the TCMSP database, and the relevant targets were selected by GeneCards, OMIM and DisGeNET databases for PCa. The cross-targets of drugs and disease were imported into the STRING database to construct protein interactions. The network was also visualized using Cytoscape software and core targets are screened using the Network Analyzer plug-in. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using R software. TCGA database was used to analyze the correlation of bioinformatics genes. AutoDock vina was used to predict the molecular docking and binding ability of active ingredients to key targets. Through WB and q-PCR experiments, the above gene targets were detected to verify the effect of LWDHD on PCa. CCK and scratch tests confirmed that LWDHD could inhibit the proliferation, invasion and migration of prostate cancer cells. Clone formation experiments showed that LWDHD inhibited the long-term proliferative capacity of PC3 cells. LWDHD and PCa had a total of 99 common targets, establishing a "drug-ingredient-common target" network. Through GO and KEGG enrichment analysis, PI3K/AKT, MAPK, TP53 pathway, MYC, TNF pathway and other signaling pathways were found. Bioinformatics analysis showed that MYC gene was highly expressed and CCND1 and MAPK1 were low expressed in prostate cancer tissues. In addition, TP53, AKT1, MYC, TNF and CCND1 were positively correlated with MAPK1, among which AKT1 and CCND1 were most closely correlated with MAPK1. Molecular docking results showed that quercetin, kaempferol, β-sitosterol and other main active ingredients of LWDHD treatment for PCa were combined with core proteins MAPK1 and AKT1 well. WB and q-PCR results showed that LWDHD inhibited the expression of PI3K and AKT in PC3 cells. The mechanism of LWDHD therapy for PCa is a multi-target and multi-pathway complex process, which may be related to the biological processes mediated by MAPK1 and AKT1 pathways, such as cell proliferation and inhibition of metastasis, and the regulation of signaling pathways. The PI3K/AKT signaling pathway may be a central pathway of LWDHD to inhibit prostate cancer proliferation.

Zhan X ，Li H ，Jin J ，Ju X ，Gao J ，Chen X ，Yuan F ，Gu J ，Xu D ，Ju G ... -  《BMC Complementary Medicine and Therapies》

Research on the Mechanism of Guizhi to Treat Nephrotic Syndrome Based on Network Pharmacology and Molecular Docking Technology.

Nephrotic syndrome (NS) is a common glomerular disease caused by a variety of causes and is the second most common kidney disease. Guizhi is the key drug of Wulingsan in the treatment of NS. However, the action mechanism remains unclear. In this study, network pharmacology and molecular docking were used to explore the underlying molecular mechanism of Guizhi in treating NS. The active components and targets of Guizhi were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Hitpick, SEA, and Swiss Target Prediction database. The targets related to NS were obtained from the DisGeNET, GeneCards, and OMIM database, and the intersected targets were obtained by Venny2.1.0. Then, active component-target network was constructed using Cytoscape software. And the protein-protein interaction (PPI) network was drawn through the String database and Cytoscape software. Next, Gene Ontology (GO) and pathway enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. And overall network was constructed through Cytoscape. Finally, molecular docking was conducted using Autodock Vina. According to the screening criteria, a total of 8 active compounds and 317 potential targets of Guizhi were chosen. Through the online database, 2125 NS-related targets were identified, and 93 overlapping targets were obtained. In active component-target network, beta-sitosterol, sitosterol, cinnamaldehyde, and peroxyergosterol were the important active components. In PPI network, VEGFA, MAPK3, SRC, PTGS2, and MAPK8 were the core targets. GO and KEGG analyses showed that the main pathways of Guizhi in treating NS involved VEGF, Toll-like receptor, and MAPK signaling pathway. In molecular docking, the active compounds of Guizhi had good affinity with the core targets. In this study, we preliminarily predicted the main active components, targets, and signaling pathways of Guizhi to treat NS, which could provide new ideas for further research on the protective mechanism and clinical application of Guizhi against NS.

He D ，Li Q ，Du G ，Sun J ，Meng G ，Chen S ... -  《-》