Network pharmacology-based strategy to investigate the active ingredients and molecular mechanisms of Scutellaria Barbata D. Don against radiation pneumonitis

AbstractDiabetic retinopathy (DR) is a leading cause of irreversible blindness globally. Qidengmingmu Capsule (QC) is a Chinese patent medicine used to treat DR, but the molecular mechanism of the treatment remains unknown. In this study, we identified and validated potential molecular mechanisms involved in the treatment of DR with QC via network pharmacology and molecular docking methods. The results of Ingredient-DR Target Network showed that 134 common targets and 20 active ingredients of QC were involved. According to the results of enrichment analysis, 2307 biological processes and 40 pathways were related to the treatment effects. Most of these processes and pathways were important for cell survival and were associated with many key factors in DR, such as vascular endothelial growth factor-A (VEGFA), hypoxia-inducible factor-1A (HIF-1Α), and tumor necrosis factor-α (TNFα). Based on the results of the PPI network and KEGG enrichment analyses, we selected AKT1, HIF-1α, VEGFA, TNFα and their corresponding active ingredients for molecular docking. According to the molecular docking results, several key targets of DR (including AKT1, HIF-1α, VEGFA, and TNFα) can form stable bonds with the corresponding active ingredients of QC. In conclusion, through network pharmacology methods, we found that potential biological mechanisms involved in the alleviation of DR by QC are related to multiple biological processes and signaling pathways. The molecular docking results also provide us with sound directions for further experiments.

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Elucidating the Mechanisms of Hugan Buzure Granule in the Treatment of Liver Fibrosis via Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/8385706 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Yi Zhu ◽

Ming Qiao ◽

Jianhua Yang ◽

Junping Hu

Keyword(s):

Liver Fibrosis ◽

Rna Polymerase Ii ◽

Molecular Mechanisms ◽

Target Genes ◽

Docking Simulation ◽

Interaction Network ◽

Network Pharmacology ◽

Transcription Activator ◽

Active Ingredients ◽

Oxidoreductase Activity

Objective. To holistically explore the latent active ingredients, targets, and related mechanisms of Hugan buzure granule (HBG) in the treatment of liver fibrosis (LF) via network pharmacology. Methods. First, we collected the ingredients of HBG by referring the TCMSP server and literature and filtered the active ingredients though the criteria of oral bioavailability ≥30% and drug-likeness index ≥0.18. Second, herb-associated targets were predicted and screened based on the BATMAN-TCM and SwissTargetPrediction platforms. Candidate targets related to LF were collected from the GeneCards and OMIM databases. Furthermore, the overlapping target genes were used to construct the protein-protein interaction network and “drug-compound-target-disease” network. Third, GO and KEGG pathway analyses were carried out to illustrate the latent mechanisms of HBG in the treatment of LF. Finally, the combining activities of hub targets with active ingredients were further verified based on software AutoDock Vina. Results. A total of 25 active ingredients and 115 overlapping target genes of HBG and LF were collected. Besides, GO enrichment analysis exhibited that the overlapping target genes were involved in DNA-binding transcription activator activity, RNA polymerase II-specific, and oxidoreductase activity. Simultaneously, the key molecular mechanisms of HBG against LF were mainly involved in PI3K-AKT, MAPK, HIF-1, and NF-κB signaling pathways. Also, molecular docking simulation demonstrated that the key targets of HBG for antiliver fibrosis were IL6, CASP3, EGFR, VEGF, and MAPK. Conclusion. This work validated and predicted the underlying mechanisms of multicomponent and multitarget about HBG in treating LF and provided a scientific foundation for further research.

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Elucidation of the active compounds and molecular mechanisms of Smilacis Chinae Rhizoma for treatment of pelvic inflammatory disease based on network pharmacology and MMGBSA-docking

10.21203/rs.3.rs-20932/v1 ◽

2020 ◽

Author(s):

Yunsen Zhang ◽

Zikuang Zhao ◽

Wenxiang Wang ◽

Qi Li ◽

Huimin Chen ◽

...

Keyword(s):

Pelvic Inflammatory Disease ◽

Signaling Pathway ◽

Inflammatory Disease ◽

Molecular Mechanisms ◽

Binding Free Energy ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Ingredients ◽

Active Compounds ◽

Bidirectional Regulation

Abstract Background Smilacis Chinae Rhizoma (SCR) is widely used in the treatment of pelvic inflammatory disease (PID). However, its active ingredients and the mechanisms against PID remain elusive. This study aimed to clarify the active ingredients and explore their molecular mechanisms on PID. Method Network pharmacology and MMGBSA-docking exploited the active compounds and mechanisms against PID, as well as validating the binding mode of candidate targets.Results Network pharmacology revealed 32 active compounds and 718 compound-related targets mapped to 91 pathways which were clustered 7 genres (e.g., immunoregulation). C-T-P network and PPI analysis illustrated 17 PID-related targets, indicating that SCR may decrease inflammation, ameliorate fibrosis, and inhibit microorganisms via bidirectionally regulating IL-17 signaling pathway. Furthermore, active compounds were uncovered that bound to prostaglandin-endoperoxide synthase 2, matrix metalloprotein-9, lipocalin, signal transducer and activator of transcription 3, myeloperoxidase, and tumor necrosis factor. 19 active compounds (e.g., rutin (-66.43 kcal/mol), moracin M (-37.01 kcal/mol) and oxyresveratrol (-38.84 kcal/mol)) were found to show excellent binding free energy, demonstrating that H-bond, Pi electron cloud and electrostatic potential as the main binding ability to these targets. Conclusion Approach of network pharmacology and MMGBSA-docking revealed the active ingredients, such as rutin, moracin M, and oxyresveratrol, in SCR and dissected it exhibits the therapeutic eﬀects (e.g., decrease inflammation, ameliorate fibrosis, and inhibit microorganisms) of PID by the bidirectional regulation of IL-17 signaling pathway.

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Deciphering the Active Ingredients and Molecular Mechanisms of Tripterygium hypoglaucum (Levl.) Hutch against Rheumatoid Arthritis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2361865 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Yunbin Jiang ◽

Mei Zhong ◽

Fei Long ◽

Rongping Yang

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Venn Diagram ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Clinical Effects ◽

Overlapping Genes ◽

Active Ingredients ◽

Tripterygium Hypoglaucum

Tripterygium hypoglaucum (Levl.) Hutch (THH) shows well clinical effect on rheumatoid arthritis (RA), but the active ingredients and molecular mechanisms remain unclear. This work was designed to explore these issues by network pharmacology. Compounds from THH were gathered by retrieving literatures. Compound-related and RA-related genes were identified using databases, and the overlapping genes were identified by Venn diagram. The active ingredients and genes of THH against RA were confirmed by dissecting interactions between overlapping genes and compounds using Cytoscape. SystemsDock website was used to further verify the combining degree of key genes with active ingredients. Pathway enrichment analysis was performed to decipher the mechanisms of THH against RA by Database for Annotation, Visualization and Integrated Discovery. A total of 123 compounds were collected, and 110 compounds-related and 1871 RA-related genes were identified, including 64 overlapping genes. The target genes and active ingredients of THH against RA comprised 64 genes and 17 compounds, the focus of which was PTGS2, triptolide, and celastrol. SystemsDock website indicated that the combing degree of PTGS2 with triptolide or celastrol was very good. The mechanisms of THH against RA were linked to 31 signaling pathways, and the key mechanism was related to inhibition of inflammation response through inactivating TNF and NF-kappa B signaling pathways. This work firstly explored the active ingredients and mechanisms of THH against RA by network pharmacology and provided evidence to support clinical effects of THH on RA.

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Deciphering of Key Pharmacological Pathways of Poria Cocos Intervention in Breast Cancer Based on Integrated Pharmacological Method

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4931531 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Xiaoran Ma ◽

Jibiao Wu ◽

Cun Liu ◽

Jie Li ◽

Shixia Dong ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Mechanisms ◽

Interaction Network ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Network Pharmacology ◽

Breast Cancers ◽

Active Ingredients ◽

Poria Cocos ◽

Pharmacological Method

Objective. Poria cocos (Fuling), a natural plant, has recently emerged as a promising strategy for cancer treatment. However, the molecular mechanisms of Poria cocos action in breast cancer remain poorly understood. Methods. TCMSP database was used to screen the potential active ingredients in Poria cocos. GEO database was used to identify differentially expressed genes. Network pharmacology was used to identify the specific pathways and key target proteins related to breast cancer. Finally, molecular docking was used to validate the results. Results. In our study, 237 targets were predicted for 15 potential active ingredients found in Poria cocos. An interaction network of predicted targets and genes differentially regulated in breast cancers was constructed. Based on the constructed network and further analysis including network topology, KEGG, survival analysis, and gene set enrichment analysis, 3 primary nodes were identified as key potential targets that were significantly enriched in the PPAR signaling pathway. Conclusion. The results showed that potential active ingredients of Poria cocos might interfere with breast cancer through synergistic regulation of PTGS2, ESR1, and FOS.

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Based on Network Pharmacology Tools to Investigate the Molecular Mechanism of Cordyceps sinensis on the Treatment of Diabetic Nephropathy

Journal of Diabetes Research ◽

10.1155/2021/8891093 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yan Li ◽

Lei Wang ◽

Bojun Xu ◽

Liangbin Zhao ◽

Li Li ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Diabetic Nephropathy ◽

Inflammatory Response ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Target Genes ◽

Cordyceps Sinensis ◽

Network Pharmacology ◽

Active Ingredients

Background. Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis. Materials and Methods. In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN. Results. Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes. Conclusions. Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.

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Network pharmacology to investigate the pharmacological mechanisms of muscone in Xingnaojing injections for the treatment of severe traumatic brain injury

PeerJ ◽

10.7717/peerj.11696 ◽

2021 ◽

Vol 9 ◽

pp. e11696

Author(s):

Zhuohang Liu ◽

Hang Li ◽

Wenchao Ma ◽

Shuyi Pan

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Chinese Medicine ◽

Signaling Pathways ◽

Neuronal Apoptosis ◽

Molecular Mechanisms ◽

Venn Diagram ◽

Network Pharmacology ◽

Active Ingredients ◽

Hub Proteins

Background Xingnaojing injections (XNJI) are widely used in Chinese medicine to mitigate brain injuries. An increasing number of studies have shown that XNJI may improve neurological function. However, XNJI’s active ingredients and molecular mechanisms when treating traumatic brain injury (TBI) are unknown. Methods XNJI’s chemical composition was acquisited from literature and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. We used the “absorption, distribution, metabolism, and excretion” (ADME) parameter-based virtual algorithm to further identify the bioactive components. We then screened data and obtained target information regarding TBI and treatment compounds from public databases. Using a Venn diagram, we intersected the information to determine the hub targets. Cytoscape was used to construct and visualize the network. In accordance with the hub proteins, we then created a protein–protein interaction (PPI) network using STRING 11.0. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed according to the DAVID bioinformatics resource database (ver. 6.8). We validated the predicted compound’s efficacy using the experimental rat chronic constriction injury (CCI) model. The neuronal apoptosis was located using the TUNEL assay and the related pathways’ hub proteins were determined by PCR, Western blot, and immunohistochemical staining. Results We identified 173 targets and 35 potential compounds belonging to XNJI. STRING analysis was used to illustrate the protein–protein interactions and show that muscone played a fundamental role in XNJI’s efficacy. Enrichment analysis revealed critical signaling pathways in these components’ potential protein targets, including PI3K/AKT1, NF-kB, and p53. Moreover, the hub proteins CASP3, BCL2L1, and CASP8 were also involved in apoptosis and were associated with PI3K/AKT, NF-kB, and p53 signaling pathways. We showed that muscone and XNJI were similarly effective 168 h after CCI, demonstrating that the muscone in XNJI significantly attenuated neuronal apoptosis through the PI3K/Akt1/NF-kB/P53 pathway. Conclusion We verified the neuroprotective mechanism in muscone for the first time in TBI. Network pharmacology offers a new approach for identifying the potential active ingredients in XNJI.

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An Integrative Pharmacology Based Analysis of Refined Liuweiwuling Against Liver Injury: A Novel Component Combination and Hepaprotective Mechanism

Frontiers in Pharmacology ◽

10.3389/fphar.2021.747010 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuan Gao ◽

Wei Shi ◽

Hongyu Yao ◽

Yongqiang Ai ◽

Ruisheng Li ◽

...

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Cell Apoptosis ◽

Liver Diseases ◽

Molecular Mechanisms ◽

Acute Liver Injury ◽

Network Pharmacology ◽

Active Ingredients ◽

Anti Inflammatory

Liver disease is a major cause of illness and death worldwide. In China, liver diseases, primarily alcoholic and nonalcoholic fatty liver disease, and viral hepatitis, affect approximately 300 million people, resulting in a major impact on the global burden of liver diseases. The use of Liuweiwuling (LWWL), a traditional Chinese medicine formula, approved by the Chinese Food and Drug Administration for decreasing aminotransferase levels induced by different liver diseases. Our previous study indicated a part of the material basis and mechanisms of LWWL in the treatment of hepatic fibrosis. However, knowledge of the materials and molecular mechanisms of LWWL in the treatment of liver diseases remains limited. Using pharmacokinetic and network pharmacology methods, this study demonstrated that the active components of LWWL were involved in the treatment mechanism against liver diseases and exerted anti-apoptosis and anti-inflammatory effects. Furthermore, esculetin, luteolin, schisandrin A and schisandrin B may play an important role by exerting anti-inflammatory and hepatoprotective effects in vitro. Esculeti and luteolin dose-dependently inhibited H2O2-induced cell apoptosis, and luteolin also inhibited the NF-κB signaling pathway in bone marrow-derived macrophages. schisandrin A and B inhibited the release of ROS in acetaminophen (APAP)-induced acute liver injury in vitro. Moreover, LWWL active ingredients protect against APAP-induced acute liver injury in mice. The four active ingredients may inhibit oxidative stress or inflammation to exert hepatoprotective effect. In conclusion, our results showed that the novel component combination of LWWL can protect against APAP-induced acute liver injury by inhibiting cell apoptosis and exerting anti-inflammatory effects.

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Exploring the Mechanisms Underlying the Therapeutic Effect of Salvia Miltiorrhiza Against Diabetic Nephropathy Using Network Pharmacology and Molecular Docking

10.21203/rs.3.rs-85980/v1 ◽

2020 ◽

Author(s):

Li-Li Zhang ◽

Lin Han ◽

Xin-Miao Wang ◽

Yu Wei ◽

Jing-Hui Zheng ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Molecular Docking ◽

Therapeutic Effect ◽

Molecular Mechanisms ◽

Function Analysis ◽

Salvia Miltiorrhiza ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Active Ingredients

Abstract BackgroundThe mechanisms underlying the therapeutic effect of Salvia Miltiorrhiza (SM) against diabetic nephropathy (DN) using systematic network pharmacology and molecular docking methods were examined.MethodsTCMSP database was used to screen the active ingredients of SM. Gene targets were obtained using Swiss Target Prediction and TCMSP databases. Related targets of DN were retrieved from the Genecards and DisGeNET databases. Next, a PPI network was constructed using the common targets of SM-DN in the STRING database. The Metascape platform was used for GO function analysis and Cytoscape plug-in ClueGO was used for KEGG pathway enrichment analysis. Molecular docking was performed using iGEMDOCK and AutoDock Vina software. Pymol and LigPlos were used for mapping the network. ResultsSixty-six active ingredients and 189 targets were screened from SM. Among them, 64 targets overlapped with DN targets. The PPI network diagram revealed that AKT1, VEGFA, IL6, TNF, MAPK1, TP53, EGFR, STAT3, MAPK14, and JUN were the top 10 relevant targets. GO and KEGG analyses mainly focused on advanced glycation end products, oxidative stress, inflammatory response, and immune regulation. Molecular docking revealed that the potential target genes closely related to DN, including TNF, NOS2, and AKT1, were more stable in combination with salvianolic acid B, and their stability was better than that of tanshinone IIA.ConclusionThis study reveals the active components and potential molecular mechanisms involved in the therapeutic effect of SM against DN and provides a reference for the wide application of SM in clinically managing DN.

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A Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of Shuilu Erxian Dan in Treating Diabetic Kidney Disease

10.21203/rs.3.rs-54579/v1 ◽

2020 ◽

Author(s):

Tingchao Wu ◽

Rensong Yue ◽

Mingmin He

Keyword(s):

Kidney Disease ◽

Signaling Pathway ◽

Diabetic Kidney Disease ◽

Molecular Mechanisms ◽

Fluid Shear Stress ◽

Experimental Studies ◽

Network Pharmacology ◽

Active Ingredients ◽

Active Components ◽

Diabetic Kidney

Abstract Background and objective: Recent years, some Chinese scholars have applied Shuilu Erxian Dan (SED) to the treatment of treating diabetic kidney disease (DKD) and achieved well curative effect. However, these studies are mostly limited to clinical observation. This study aimed to explore the molecular mechanisms of SED in treating DKD. Methods The active components of SED were retrieved in TCMSP database and BATMAN-TCM database, and the herbal targets were obtained by drugbank database and SwissTargetPrediction platform. The gene expression data of DKD patients were downloaded from GEO database and analyzed to obtain DKD-related targets. The ingredient-target network and the PPI network were constructed by Cytoscape software. The clusterProfiler package of R software is used for bioinformatic analysis. Molecular docking was further applied to verify the interaction between compounds and targets by Autodock Vina software. Results 610 differential expressed genes of DKD patients were obtained, and 29 potential targets of SED against DKD were screened out (including PPTGS2, FABP3, HSD17B2, FABP1, HSD11B2, CYP27B1, JUN, UGT2B7, VCAM1, CA2, MAOA, MMP2, CXCR1, SLC22A6, EPHX2, SLC47A1, FOS, EGF, CCL2, COL3A1, GSTA1, GSTA2, HSPA1A, DAO, ALDH2, ALB, GPR18, FPR2, and LPL). All the active ingredients in SED can act on the DKD-related targets, among which quercetin, Ellagic acid, and kaempferol may be the key active compounds. SED may play a therapeutic role in DKD by regulating pathways including “Fluid shear stress and atherosclerosis”, “AGE − RAGE signaling pathway in diabetic complications” and “IL-17 signaling pathway”. Conclusion This study suggests that the mechanism of SED treating DKD is a complex network with multi-target and multi-pathway, which provides a reference for future experimental studies.

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