scholarly journals The Effect of Hedysarum multijugum Maxim.-Chuanxiong rhizoma Compound on Ischemic Stroke: A Research Based on Network and Experimental Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-24
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yongmei Shi ◽  
Xiaofei Zhu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Ischemic Stroke ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathways ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Buyang Huanwu Decoction

Background. Hedysarum multijugum Maxim.-Chuanxiong rhizoma compound (HCC) is a common herbal formula modified from Buyang Huanwu decoction. Clinical trials have demonstrated its therapeutic potential for ischemic stroke (IS). However, the mechanism of HCC remains unclear. Methods. The HCC’s components were collected from the TCMSP database and TCM@Taiwan database. After that, the HCC’s compound targets were predicted by PharmMapper. The IS-related genes were obtained from GeneCards, and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from the String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis and the Cytoscape 3.7.2 was utilized to construct and analyze the networks. Finally, a series of animal experiments were carried out to validate the prediction results of network pharmacology. The expressions of GRP78, p-PERK, and CHOP proteins and mRNAs in different time periods after HCC intervention were detected by Western blot, immunohistochemistry, and RT-qPCR. Results. A total of 440 potential targets and 388 IS genes were obtained. The results of HCC-IS PPI network analysis showed that HCC may regulate IS-related targets (such as ALB, AKT1, MMP9, IGF1, and CASP3), biological processes (such as endoplasmic reticulum stress, inflammation modules, hypoxia modules, regulation of neuronal apoptosis and proliferation, and angiogenesis), and signaling pathways (such as PI3K-Akt, FoxO, TNF, HIF-1, and Rap1 signaling). The animal experiments showed that HCC can improve the neurobehavioral scores and protect the neurons of IS rats ( P < 0.05 ). HCC inhibited the expression of p-PERK in the PERK pathway from 12 h after surgery, significantly promoted the expression of GRP78 protein, and inhibited the expression of CHOP protein after surgery, especially at 24 h after surgery ( P < 0.05 ). The results of RT-qPCR showed that HCC can significantly reduce the expression of CHOP mRNA in the neurons in the CA1 region of the hippocampus 72 h after MCAO ( P < 0.05 ). Conclusion. HCC may achieve a role in the treatment of IS by intervening in a series of targets, signaling pathways, and biological processes such as inflammation, oxidative stress, endoplasmic reticulum stress, and angiogenesis.

scholarly journals Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yi Chen ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathways ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemic

Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained.Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR.Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p &lt; 0.05).Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.

scholarly journals Exploring the Pharmacological Mechanism of Liuwei Dihuang Decoction for Diabetic Retinopathy: A Systematic Biological Strategy-Based Research

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Mengxia Yuan ◽  
Qi He ◽  
Zhiyong Long ◽  
Xiaofei Zhu ◽  
Wang Xiang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Signaling Pathways ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Ppi Network ◽  
Pharmacological Mechanism ◽  
Target Network ◽  
Erbb Signaling

Objective. To explore the pharmacological mechanism of Liuwei Dihuang decoction (LDD) for diabetic retinopathy (DR). Methods. The potential targets of LDD were predicted by PharmMapper. GeneCards and other databases were used to collect DR genes. Cytoscape was used to construct and analyze network DR and LDD’s network, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were carried out to verify the results of systematic pharmacology. Results. Five networks were constructed and analyzed: (1) diabetic retinopathy genes’ PPI network; (2) compound-compound target network of LDD; (3) LDD-DR PPI network; (4) compound-known target network of LDD; (5) LDD known target-DR PPI network. Several DR and treatment-related targets, clusters, signaling pathways, and biological processes were found. Animal experiments found that LDD can improve the histopathological changes of the retina. LDD can also increase erythrocyte filtration rate and decrease the platelet adhesion rate ( P < 0.05 ) and decrease MDA and TXB2 ( P < 0.05 ). Compared with the model group, the retinal VEGF and HIF-1α expression in the LDD group decreased significantly ( P < 0.05 ). Conclusion. The therapeutic effect of LDD on DR may be achieved by interfering with the biological processes (such as response to insulin, glucose homeostasis, and regulation of angiogenesis) and signaling pathways (such as insulin, VEGF, HIF-1, and ErbB signaling pathway) related to the development of DR that was found in this research.

scholarly journals Analysis of the Molecular Mechanisms of the Effects of Prunella vulgaris against Subacute Thyroiditis Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xin Shen ◽  
Rui Yang ◽  
Jianpeng An ◽  
Xia Zhong
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Subacute Thyroiditis ◽  
Network Pharmacology ◽  
Pharmacokinetic Parameters ◽  
Pathway Enrichment Analysis ◽  
Prunella Vulgaris ◽  
Protein Protein Interaction

Prunella vulgaris (PV) has a long history of application in traditional Chinese and Western medicine as a remedy for the treatment of subacute thyroiditis (SAT). This study applied network pharmacology to elucidate the mechanism of the effects of PV against SAT. Components of the potential therapeutic targets of PV and SAT-related targets were retrieved from databases. To construct a protein-protein interaction (PPI) network, the intersection of SAT-related targets and PV-related targets was input into the STRING platform. Gene ontology (GO) analysis and KEGG pathway enrichment analysis were carried out using the DAVID database. Networks were constructed by Cytoscape for visualization. The results showed that a total of 11 compounds were identified according to the pharmacokinetic parameters of ADME. A total of 126 PV-related targets and 2207 SAT-related targets were collected, and 83 overlapping targets were subsequently obtained. The results of the KEGG pathway and compound-target-pathway (C-T-P) network analysis suggested that the anti-SAT effect of PV mainly occurs through quercetin, luteolin, kaempferol, and beta-sitosterol and is most closely associated with their regulation of inflammation and apoptosis by targeting the PIK3CG, MAPK1, MAPK14, TNF, and PTGS2 proteins and the PI3K-Akt and TNF signaling pathways. The study demonstrated that quercetin, luteolin, kaempferol, and beta-sitosterol in PV may play a major role in the treatment of SAT, which was associated with the regulation of inflammation and apoptosis, by targeting the PI3K-Akt and TNF signaling pathways.

scholarly journals A System-Level Investigation into the Mechanisms of Apigenin Against Inflammation

2019 ◽  
Vol 14 (9) ◽  
pp. 1934578X1987860 ◽  
Author(s):  
Ying Xie ◽  
Dongdong Liang ◽  
Qingke Wu ◽  
Xuemei Chen ◽  
Manal Ali Buabeid ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Biological Activities ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
System Level ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Go Terms

Apigenin is a natural flavone that possesses excellent biological activities especially against aging and cancer. However, the underlying mode of its action is not yet revealed. The purpose of this study was to examine the pharmacological mechanisms of apigenin using the knowledge of network pharmacology, protein-protein interaction (PPI) databases and biological processes analysis through Cytoscape. Apigenin targets were retrieved through PASS Prediction and STITCH database and the interactive associations between these targets were studied using STITCH, followed by GO (gene ontology) and pathway enrichment analysis. As a result of target search, 125 protein targets were retrieved. Moreover, 216 GO terms related to various biological processes, 16 GO terms for various molecular processes, 5 GO terms for the cellular components, and 52 Kyoto Encyclopedia of Genes and Genomes pathway terms were achieved by analyzing gene functional annotation clusters and abundance values of these targets. Most of these terms are strongly associated with inflammation through various pathways, for example, FOXO, mammalian target of rapamycin, tumor necrosis factor, p53, AMP-activated protein kinase, p13K-AKT, and mitogen-activated protein kinase, which play an important role in inflammation, aging and cancer. Apigenin can be used to treat inflammation, aging, and cancer with an underlying mechanism of inflammation suppression. This study contributed excellent information for a better understanding of the modes of action of apigenin. However, further studies such as docking and MD simulation are required to understand the therapeutic and toxicological roles of these targets of apigenin.

scholarly journals Network Pharmacology-Based Study on the Mechanism of Pinellia ternata in Asthma Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yanmin Lyu ◽  
Xiangjing Chen ◽  
Qing Xia ◽  
Shanshan Zhang ◽  
Chengfang Yao
Keyword(s):  
Candidate Genes ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Th2 Cells ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Pinellia Ternata

Background. Pinellia ternata (PT), a medicinal plant, has had an extensive application in the treatment of asthma in China, whereas its underlying pharmacological mechanisms remain unclear. Methods. Firstly, a network pharmacology method was adopted to collect activated components of PT from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets of PT were assessed by exploiting the PharmMapper website; asthma-related targets were collected from the OMIM website, and target-target interaction networks were built. Secondly, critical nodes exhibiting high possibility were identified as the hub nodes in the network, which were employed to conduct Gene Ontology (GO) comment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the tissue expression profiles of key candidate genes were identified by the Gene Expression Omnibus (GEO) database, and the therapeutic effect of PT was verified by an animal experiment. Results. 57 achievable targets of PT on asthma were confirmed as hub nodes through using the network pharmacology method. As revealed from the KEGG enrichment analysis, the signaling pathways were notably enriched in pathways of the T-cell receptor signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction. The expression profiles of candidate genes including Mmp2, Nr3c1, il-10, il-4, il-13, il-17a, il-2, tlr4, tlr9, ccl2, csf2, and vefgα were identified. Moreover, according to transcriptome RNA sequencing data from lung tissues of allergic mice compared to normal mice, the mRNA level of Mmp2 and il-4 was upregulated ( P < 0.001 ). In animal experiments, PT could alleviate the allergic response of mice by inhibiting the activation of T-helper type 2 (TH2) cells and the expression of Mmp2 and il-4. Conclusions. Our study provides candidate genes that may be either used for future studies related to diagnosis/prognosis or as targets for asthma management. Besides, animal experiments showed that PT could treat asthma by regulating the expression of Mmp2 and il-4.

scholarly journals Integrating Network Pharmacology and Experimental Validation Deciphers the Mechanism of Guizhi Fuling Wan against Adenomyosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Haoxian Wang ◽  
Jihong Zhang ◽  
Qinqin Zhu ◽  
Xianyun Fu ◽  
Chenjie Li
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Verification Methods

Aim. This study aimed to predict the key targets and endocrine mechanisms of Guizhi Fuling Wan (GZFLW) in treating adenomyosis (AM) through network pharmacology, molecular docking, and animal experiment verification. Methods. The related ingredients and targets of GZFLW in treating AM were screened out using TCMSP, BATMAN-TCM, SwissTargetPrediction, and PubChem Database. Then, the protein-protein interaction (PPI) analysis and the network of compound-hub targets were constructed. At the same time, the key targets were uploaded to the Metascape Database for KEGG pathway enrichment analysis. After that, the molecular docking technology of the main active components and hub targets was performed. Furthermore, animal experiments were used to verify the results of network pharmacology analysis. Results. A total of 55 active ingredients of GZFLW and 44 overlapping targets of GZFLW in treating AM were obtained. After screening, 25 hub targets were collected, including ESR1, EGF, and EGFR. Then, the KEGG pathway enrichment analysis results indicated that the endocrine therapeutic mechanism of GZFLW against AM is mainly associated with the estrogen signaling pathway, endocrine resistance, and an EGFR tyrosine kinase signaling pathway. Then, molecular docking showed that the significant compounds of GZFLW had a strong binding ability with ERα and EGFR. More importantly, the animal experiments confirmed that the GZFLW could downregulate the abnormal infiltration of the endometrial epithelium into the myometrium and had no interference with the normal sexual cycle. This effect may be directly related to intervening the local estrogen signaling pathway of the endometrial myometrial interface (EMI). It may also be associated with the myometrium cells’ estrogen resistance via GPER/EGFR signaling pathway. Conclusion. The endocrine mechanism of GZFLW in treating AM was explored based on network pharmacology, molecular docking, and animal experiments, which provided a theoretical basis for the clinical application of GZFLW.

scholarly journals Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xiang Yu ◽  
Peng Zhang ◽  
Kai Tang ◽  
Gengyang Shen ◽  
Honglin Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Signaling Pathways ◽  
Osteoporotic Fracture ◽  
Hydrophobic Interactions ◽  
Osteoclast Differentiation ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
The Core

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis ( P < 0.05 ), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included ( P < 0.05 ), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3–9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.

scholarly journals Mechanism of Youguiyin in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Yi Pan ◽  
Wanlu Zhao ◽  
Luping Qin ◽  
Lu Zhang
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Transcriptional Gene Silencing ◽  
Pathway Enrichment Analysis ◽  
Signal Pathways ◽  
Biological Processes ◽  
The Core ◽  
Material Basis

Abstract Background: Youguiyin (YGY) has been confirmed to treat osteoporosis (OP) in clinical trials, but its specific pharmacological mechanism remains unclear. This study aimed to explore the material basis and potential mechanism of YGY in the treatment of OP based on network pharmacology and molecular docking.Methods: Databases including TCMSP, SwissTargetPrediction database, OMIM, and TTD were used to predict the effective ingredients and relevant targets of YGY in the treatment of OP. The STRING database was used to reveal the relationship between each intersection target protein. Metascape database was used to perform GO enrichment analysis and KEGG pathway enrichment analysis on the intersection targets. Cytoscape 3.6.0 software was used to show the complex network relationship of YGY in the treatment of OP. According to the results of network characteristics analysis, the core effective ingredients and the core targets were screened out. Autodock 4.0 was used for molecular docking and Pymol was used to visualize the docking results.Results: 290 effective ingredients, 1127 targets of the effective ingredients, 273 relevant targets of OP and 17 intersection targets were screened out in total by searching literature and databases. Intersection targets could affect biological processes including regulation of inflammatory response, ossification, negative regulation of post-transcriptional gene silencing, positive regulation of cytokine biosynthetic process and regulation of hormone levels by regulating signal pathways including TNF signaling pathway, osteoclast differentiation, apoptosis, MAPK signaling pathway and PI3K/Akt signaling pathway. Through screening, 14 core effective ingredients and 6 core targets were confirmed. The results of molecular docking showed that most of the core effective ingredients including α-humulene, cinnamaldehyde, denudatine, benzoylhypaconine and quercetin had good binding activity with the core targets including TNF-α, IL-1β and IL-6.Conclusion: Based on network pharmacology and molecular docking, the critical effective ingredients, key targets, important signal pathways and main biological processes of YGY in the treatment of OP were successfully screened out. This study revealed the material basis and the mechanism of YGY in the treatment of OP and provided a theoretical basis for follow-up experimental research and clinical application of YGY.

scholarly journals Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Buyang Huanwu Decoction in the Treatment of Ischemic Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Qiang Gao ◽  
Danfeng Tian ◽  
Zhenyun Han ◽  
Jingfeng Lin ◽  
Ze Chang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Molecular Docking ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Ppi Network ◽  
Active Components ◽  
Nf Kappa B ◽  
Buyang Huanwu Decoction ◽  
Pathway Network ◽  
Target Network

Background and Objective. With the exact clinical efficacy, Buyang Huanwu decoction (BHD) is a classical prescription for the treatment of ischemic stroke (IS). Here, we aimed to investigate the pharmacological mechanisms of BHD in treating IS using systems biology approaches. Methods. The bioactive components and potential targets of BHD were screened by TCMSP, BATMAN-TCM, ETCM, and SymMap databases. Besides, compounds that failed to find the targets from the above databases were predicted through STITCH, SwissTargetPrediction, and SEA. Moreover, six databases were searched to mine targets of IS. The intersection targets were obtained and analyzed by GO and KEGG enrichment. Furthermore, BHD-IS PPI network, compound-target network, and herb-target-pathway network were constructed by Cytoscape 3.6.0. Finally, AutoDock was used for molecular docking verification. Results. A total of 235 putative targets were obtained from 59 active compounds in BHD. Among them, 62 targets were related to IS. PPI network showed that the top ten key targets were IL6, TNF, VEGFA, AKT1, etc. The enrichment analysis demonstrated candidate BHD targets were more frequently involved in TNF, PI3K-Akt, and NF-kappa B signaling pathway. Network topology analysis showed that Radix Astragali was the main herb in BHD, and the key components were quercetin, beta-sitosterol, kaempferol, stigmasterol, etc. The results of molecular docking showed the active components in BHD had a good binding ability with the key targets. Conclusions. Our study demonstrated that BHD exerted the effect of treating IS by regulating multitargets and multichannels with multicomponents through the method of network pharmacology and molecular docking.

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