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

PeerJ ◽  
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.

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

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
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.

scholarly journals Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Ying Huang ◽  
Wen-jiang Zheng ◽  
Yong-shi Ni ◽  
Mian-sha Li ◽  
Jian-kun Chen ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Integrated Network ◽  
Therapeutic Mechanism ◽  
The World

Abstract Background Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. Methods TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a “drug-active ingredient-potential target” network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. Results A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of “drug-component-target-biological process-signaling pathway”. Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. Conclusions Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

A network pharmacology approach to explore the mechanisms of action of Epimrdii Herba-Coicis Semen for treatment of Alzheimer's disease

2020 ◽  
Author(s):  
Yuxuan Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Pharmacokinetic Parameters ◽  
Neuron Death

Abstract Background: Traditional Chinese medicine (TCM) can treat diseases through its “multi-component, multi-target, multi-pathway” mechanisms. Especially have advantages in the treatment of diseases with complicated pathogenesis, such as Alzheimer’s disease (AD). Tonifying the kidney and strengthening the spleen is one of the common methods of Chinese Medicine to treat AD. The TCM combination of Epimrdii Herba and Coicis Semen can be used as the main drugs of a prescription for tonifying the kidney and strengthening the spleen. However, the mechanisms for Epimrdii Herba-Coicis Semen (EH-CS) to treat AD is vague. The purpose of this study was to explore the mechanisms of EH-CS on AD using a network pharmacological method.Methods: We retrieved the chemical compounds and targets of Epimrdii Herba-Coicis Semen from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). We screened the active ingredients based on the pharmacokinetic parameters (ADME). The Human Gene Database (GeenCards) was used to obtain disease targets of Alzheimer’s disease. Then we drew a venn diagram to obtain common targets of Chinese medicine and disease. Based on the topological properties, we screened the key targets. The protein-protein interaction (PPI) network was constructed using the STRING database, and the "Traditional Chinese Medicine-active ingredient-target" network was constructed using Cytoscape software. The key targets were respectively uploaded to the Metascape and DAVID database for GO and KEGG pathway analysis.Results: We obtained 31 active compounds for EH-CS. Flavonoids play important roles in the treatment of AD. A total of 29 key targets, including AKT1, MAPK1, and TP53, etc. The biological processes involve response to lipopolysaccharide, neuron death, neuroinflammatory response, etc. The main pathways include TNF signaling pathways, MAPK signaling pathways, PI3K-Akt signaling pathways and other signaling pathways.Conclusion: The network pharmacology method is an effective tool for exploring the mechanisms of TCM. Based on network pharmacology, this study systematically explained the potential mechanisms of EH-CS on AD. It provides a valuable reference for the development of AD drugs.

scholarly journals Network pharmacology and molecular docking study on the mechanism of colorectal cancer treatment using Xiao-Chai-Hu-Tang

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252508
Author(s):  
Jingyun Jin ◽  
Bin Chen ◽  
Xiangyang Zhan ◽  
Zhiyi Zhou ◽  
Hui Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathways ◽  
Target Genes ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Active Ingredients ◽  
Molecular Docking Study

Background and objective We aimed to predict the targets and signal pathways of Xiao-Chai-Hu-Tang (XCHT) in the treatment of colorectal cancer (CRC) based on network pharmacology, just as well as to further analyze its anti-CRC material basis and mechanism of action. Methods We adopted Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) databases to screen the active ingredients and potential targets of XCHT. CRC-related targets were retrieved by analyzing published microarray data (accession number GSE110224) from the Gene Expression Omnibus (GEO) database. The common targets were used to construct the “herb-active ingredient-target” network using the Cytoscape 3.8.0 software. Next, we constructed and analyzed protein-to-protein interaction (PPI) using BisoGenet and CytoNCA plug-in in Cytoscape. We then performed Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes using the R package of clusterProfiler. Furthermore, we used the AutoDock Tools software to conduct molecular docking studies on the active ingredients and key targets to verify the network pharmacological analysis results. Results We identified a total of 71 active XCHT ingredients and 20 potential anti-CRC targets. The network analysis revealed quercetin, stigmasterol, kaempferol, baicalein, and acacetin as potential key compounds, and PTGS2, NR3C2, CA2, and MMP1 as potential key targets. The active ingredients of XCHT interacted with most CRC disease targets. We showed that XCHT’s therapeutic effect was attributed to its synergistic action (multi-compound, multi-target, and multi-pathway). Our GO enrichment analysis showed 46 GO entries, including 20 biological processes, 6 cellular components, and 20 molecular functions. We identified 11 KEGG signaling pathways, including the IL-17, TNF, Toll-like receptor, and NF-kappa B signaling pathways. Our results showed that XCHT could play a role in CRC treatment by regulating different signaling pathways. The molecular docking experiment confirmed the correlation between five core compounds (quercetin, stigmasterol, kaempferol, baicalein, and acacetin) just as well as PTGS2, NR3C2, CA2, and MMP1. Conclusion In this study, we described the potential active ingredients, possible targets, and key biological pathways responsible for the efficacy of XCHT in CRC treatment, providing a theoretical basis for further research.

scholarly journals Exploring the Effects of Changping Decoction on Irritable Bowel Syndrome by Pathway and Pharmacology Network Bioinformatics Analysis

2020 ◽  
Author(s):  
Guo-Jie Hu ◽  
Ding Li ◽  
Shi-Fang Li ◽  
Xiao-Yuan Li ◽  
Xiao-Wei Sun ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathways ◽  
Network Pharmacology ◽  
Potential Mechanism ◽  
Active Ingredients ◽  
Hub Genes ◽  
Withdrawal Reflex ◽  
Irritable Bowel

Abstract Background An increasing body of research has confirmed the effectiveness of Traditional Chinese Medicine (TCM) for the treatment of irritable bowel syndrome (IBS).Methods We explored the potential mechanism of Changping decoction (CPD) in the treatment of IBS through pathway analysis based on a network pharmacology approach. Public databases, including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Gene Expression Omnibus, and STRING, were used to screen the active ingredients and targets of CPD. Enrichment analysis was performed using the R-3.6.0 software to expound the biological functions and related pathways of CPD targets. The Cytoscape software was used to construct a “disease-CPD-target” network and identify hub genes of CPD relevant for the treatment of IBS. Employing rat models, pathological observation and abdominal withdrawal reflex tests were used to verify the effectiveness of CPD in the treatment of IBS. Immunohistochemistry was used to confirm the relationship between the CPD treatment and hub genes.Results Network pharmacological analysis of CPD for the treatment of IBS identified 159 active ingredients. A total of 118 key targets were identified, including MAPK8, VEGFA, PTGS2, and others. A series of signaling pathways, such as MAPK, Kaposi sarcoma-associated herpesvirus infection, and IL-17 signaling pathway were found to play an important role in the therapeutic mechanism of CPD in the treatment of IBS. Pathological observation and abdominal withdrawal reflex tests confirmed that the symptoms of IBS in rats were relieved by CPD. Moreover, immunohistochemistry confirmed that CPD could inhibit the expression of inflammation-associated factors, such as VEGFA, MAPK8, and PTGS2.Conclusions Based on network pharmacology analysis, the present study provides insights into the potential mechanism of CPD in the treatment of IBS after successfully screening for associated key target genes and signaling pathways. These findings establish a theoretical basis for the development of CPD-derived therapeutics.

FGF10 Attenuates Experimental Traumatic Brain Injury through TLR4/MyD88/NF-κB Pathway

2021 ◽  
pp. 1-9
Author(s):  
Qinhan Hou ◽  
Hongmou Chen ◽  
Quan Liu ◽  
Xianlei Yan
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Water Content ◽  
Neurological Deficit ◽  
Neuronal Apoptosis ◽  
Neuronal Damage ◽  
Intraventricular Injection ◽  
Brain Water Content ◽  
Brain Water

Traumatic brain injury (TBI) can induce neuronal apoptosis and neuroinflammation, resulting in substantial neuronal damage and behavioral disorders. Fibroblast growth factors (FGFs) have been shown to be critical mediators in tissue repair. However, the role of FGF10 in experimental TBI remains unknown. In this study, mice with TBI were established via weight-loss model and validated by increase of modified neurological severity scores (mNSS) and brain water content. Secondly, FGF10 levels were elevated in mice after TBI, whereas intraventricular injection of Ad-FGF10 decreased mNSS score and brain water content, indicating the remittance of neurological deficit and cerebral edema in TBI mice. In addition, neuronal damage could also be ameliorated by stereotactic injection of Ad-FGF10. Overexpression of FGF10 increased protein expression of Bcl-2, while it decreased Bax and cleaved caspase-3/PARP, and improved neuronal apoptosis in TBI mice. In addition, Ad-FGF10 relieved neuroinflammation induced by TBI and significantly reduced the level of interleukin 1β/6, tumor necrosis factor α, and monocyte chemoattractant protein-1. Moreover, Ad-FGF10 injection decreased the protein expression level of Toll-like receptor 4 (TLR4), MyD88, and phosphorylation of NF-κB (p-NF-κB), suggesting the inactivation of the TLR4/MyD88/NF-κB pathway. In conclusion, overexpression of FGF10 could ameliorate neurological deficit, neuronal apoptosis, and neuroinflammation through inhibition of the TLR4/MyD88/NF-κB pathway, providing a potential therapeutic strategy for brain injury in the future.

scholarly journals Traumatic Brain Injury Impairs Systemic Vascular Function Through Disruption of Inward-Rectifier Potassium Channels

Function ◽  
2021 ◽  
Author(s):  
Adrian M Sackheim ◽  
Nuria Villalba ◽  
Maria Sancho ◽  
Osama F Harraz ◽  
Adrian D Bonev ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Potassium Channels ◽  
Signaling Pathways ◽  
Inward Rectifier ◽  
Pla2 Activity ◽  
Functional Responses ◽  
Channel Function ◽  
Inward Rectifier Potassium Channels ◽  
Kir2.1 Channel

Abstract Trauma can lead to widespread vascular dysfunction, but the underlying mechanisms remain largely unknown. Inward-rectifier potassium channels (Kir2.1) play a critical role in the dynamic regulation of regional perfusion and blood flow. Kir2.1 channel activity requires phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid that is degraded by phospholipase A2 (PLA2) in conditions of oxidative stress or inflammation. We hypothesized that PLA2–induced depletion of PIP2 after trauma impairs Kir2.1 channel function. A fluid percussion injury model of traumatic brain injury (TBI) in rats was used to study mesenteric resistance arteries 24 hours after injury. The functional responses of intact arteries were assessed using pressure myography. We analyzed circulating PLA2, hydrogen peroxide (H2O2), and metabolites to identify alterations in signaling pathways associated with PIP2 in TBI. Electrophysiology analysis of freshly-isolated endothelial and smooth muscle cells revealed a significant reduction of Ba2+-sensitive Kir2.1 currents after TBI. Additionally, dilations to elevated extracellular potassium and BaCl2- or ML 133-induced constrictions in pressurized arteries were significantly decreased following TBI, consistent with an impairment of Kir2.1 channel function. The addition of a PIP2 analog to the patch pipette successfully rescued endothelial Kir2.1 currents after TBI. Both H2O2 and PLA2 activity were increased after injury. Metabolomics analysis demonstrated altered lipid metabolism signaling pathways, including increased arachidonic acid, and fatty acid mobilization after TBI. Our findings support a model in which increased H2O2-induced PLA2 activity after trauma hydrolyzes endothelial PIP2, resulting in impaired Kir2.1 channel function.

scholarly journals Network pharmacology and molecular docking study on the active ingredients of qidengmingmu capsule for the treatment of diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mingxu Zhang ◽  
Jiawei Yang ◽  
Xiulan Zhao ◽  
Ying Zhao ◽  
Siquan Zhu
Keyword(s):  
Diabetic Retinopathy ◽  
Molecular Docking ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Enrichment Analysis ◽  
Docking Study ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Ingredients ◽  
Molecular Docking Study

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.

Novel Synthetic and Natural Therapies for Traumatic Brain Injury

2021 ◽  
Vol 19 ◽  
Author(s):  
Denise Battaglini ◽  
Dorota Siwicka-Gieroba ◽  
Patricia RM Rocco ◽  
Fernanda Ferreira Cruz ◽  
Pedro Leme Silva ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Secondary Brain Injury ◽  
Specific Recommendation ◽  
Novel Therapies ◽  
Secondary Brain Damage ◽  
Late Treatment

: Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by a dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage-such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in inhibition of secondary brain injury can result as potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies basing on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.

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