scholarly journals Assessing the Anti-inflammatory Mechanism of Reduning Injection by Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Fuda Xie ◽  
Mingxiang Xie ◽  
Yibing Yang ◽  
Miaomiao Zhang ◽  
Xiaojie Xu ◽  
...  
Keyword(s):  
Data Mining ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Inflammatory Diseases ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Inflammatory Mechanism ◽  
Reduning Injection ◽  
Anti Inflammatory

Reduning Injection (RDNI) is a traditional Chinese medicine formula indicated for the treatment of inflammatory diseases. However, the molecular mechanism of RDNI is unclear. The information of RDNI ingredients was collected from previous studies. Targets of them were obtained by data mining and molecular docking. The information of targets and related pathways was collected in UniProt and KEGG. Networks were constructed and analyzed by Cytoscape to identify key compounds, targets, and pathways. Data mining and molecular docking identified 11 compounds, 84 targets, and 201 pathways that are related to the anti-inflammatory activity of RDNI. Network analysis identified two key compounds (caffeic acid and ferulic acid), five key targets (Bcl-2, eNOS, PTGS2, PPARA, and MMPs), and four key pathways (estrogen signaling pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway) which would play critical roles in the treatment of inflammatory diseases by RDNI. The cross-talks among pathways provided a deeper understanding of anti-inflammatory effect of RDNI. RDNI is capable of regulating multiple biological processes and treating inflammation at a systems level. Network pharmacology is a practical approach to explore the therapeutic mechanism of TCM for complex disease.

scholarly journals Integrating Data Mining, Network Pharmacology, and Molecular Docking Verification to Investigate the Molecular Mechanism of Traditional Chinese Medicine Prescriptions for Treating Male Infertility

2021 ◽  
Author(s):  
Xue Bai ◽  
Yibo Tang ◽  
Qiang Li ◽  
Guimin Liu ◽  
Dan Liu ◽  
...  
Keyword(s):  
Data Mining ◽  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Male Infertility ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Oxidant Stress ◽  
Estrogen Signaling ◽  
Network Pharmacology

Abstract Background: Male infertility (MI) affects almost 5% adult men worldwide, and 75% of these cases are unexplained idiopathic. There are limitations in the current treatment due to the unclear mechanism of MI, which highlight the urgent need for a more effective strategy or drug. Traditional Chinese Medicine (TCM) prescriptions have been used to treat MI for thousands of years, but their molecular mechanism is not well defined. Methods: Aiming at revealing the molecular mechanism of TCM prescriptions on MI, a comprehensive strategy integrating data mining, network pharmacology, and molecular docking verification was performed. Firstly, we collected 289 TCM prescriptions for treating MI from National Institute of TCM Constitution and Preventive Medicine for 6 years. Then, Core Chinese Materia Medica (CCMM), the crucial combination of TCM prescriptions, was obtained by the TCM Inheritance Support System from China Academy of Chinese Medical Sciences. Next, the components and targets of CCMM in TCM prescriptions and MI-related targets were collected and analyzed through network pharmacology approach.Results: The results showed that the molecular mechanism of TCM prescriptions for treating MI are regulating hormone, inhibiting apoptosis, oxidant stress and inflammatory. Estrogen signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway are the most important signaling pathways. Molecular docking experiments were used to further validate network pharmacology results. Conclusions: This study not only discovers CCMM and the molecular mechanism of TCM prescriptions for treating MI, but may be helpful for the popularization and application of TCM treatment.

scholarly journals Study on the Mechanism of Acori Graminei Rhizoma in the Treatment of Alzheimer’s Disease Based on Network Pharmacology and Molecular Docking

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yi Kuan Du ◽  
Yue Xiao ◽  
Shao Min Zhong ◽  
Yi Xing Huang ◽  
Qian Wen Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
The Elderly ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Active Components

Alzheimer’s disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer’s disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of “drug-active ingredient-ingredient target.” A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer’s disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer’s signal pathway, thus reducing the production of Aβ, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.

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 Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

2022 ◽  
Vol 12 ◽  
Author(s):  
Jinlong Zhao ◽  
Fangzheng Lin ◽  
Guihong Liang ◽  
Yanhong Han ◽  
Nanjun Xu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Active Components ◽  
Treatment Of Osteoporosis ◽  
Effective Components

ObjectiveTo explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods.MethodsThe effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software.ResultsA total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components.ConclusionsPR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.

scholarly journals Melatonin: Multi-Target Mechanism Against Diminished Ovarian Reserve Based on Network Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Liuqing Yang ◽  
Hongbin Xu ◽  
Yun Chen ◽  
Chenyun Miao ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Immune System ◽  
Signaling Pathway ◽  
Ovarian Reserve ◽  
Target Identification ◽  
Therapeutic Targets ◽  
Diminished Ovarian Reserve ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Immune System Regulation

BackgroundDiminished ovarian reserve (DOR) significantly increases the risk of female infertility and contributes to reproductive technology failure. Recently, the role of melatonin in improving ovarian reserve (OR) has attracted widespread attention. However, details on the pharmacological targets and mechanisms of melatonin-improved OR remain unclear.ObjectiveA systems pharmacology strategy was proposed to elucidate the potential therapeutic mechanism of melatonin on DOR at the molecular, pathway, and network levels.MethodsThe systems pharmacological approach consisted of target identification, data integration, network construction, bioinformatics analysis, and molecular docking.ResultsFrom the molecular perspective, 26 potential therapeutic targets were identified. They participate in biological processes related to DOR development, such as reproductive structure development, epithelial cell proliferation, extrinsic apoptotic signaling pathway, PI3K signaling, among others. Eight hub targets (MAPK1, AKT1, EGFR, HRAS, SRC, ESR1, AR, and ALB) were identified. From the pathway level, 17 significant pathways, including the PI3K-Akt signaling pathway and the estrogen signaling pathway, were identified. In addition, the 17 signaling pathways interacted with the 26 potential therapeutic targets to form 4 functional modules. From the network point of view, by regulating five target subnetworks (aging, cell growth and death, development and regeneration, endocrine and immune systems), melatonin could exhibit anti-aging, anti-apoptosis, endocrine, and immune system regulation effects. The molecular docking results showed that melatonin bound well to all hub targets.ConclusionThis study systematically and intuitively illustrated the possible pharmacological mechanisms of OR improvement by melatonin through anti-aging, anti-apoptosis, endocrine, and immune system regulation effects.

scholarly journals Molecular mechanism of luteolin against inflammation based on integration of network pharmacology, transcriptomics and proteomics

2020 ◽  
Author(s):  
XiuFang Huang ◽  
Jia-Lin Zhang ◽  
Ai-Si Huang ◽  
Dan-Ping Huang ◽  
Hui-Ting Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Gene Function ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Mrna Levels ◽  
Pathway Enrichment ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory ◽  
Core Genes ◽  
Inflammatory Effect

Abstract Background: Luteolin (3', 4', 5,7-tetrahydroxyflavone), a natural flavonoid exists in various medicinal plants, has strong anti-inflammatory effect. However, anti-inflammatory mechanism of luteolin has not been fully explored. Hence, we aimed to systematically investigate druggability and anti-inflammatory mechanism of luteolin based on network pharmacology. Methods: The absorption, distribution, metabolism, excretion, and toxicity of luteolin were evaluated by TCMSP server. Targets associated with luteolin and inflammation were collected from public databases, and the overlapping targets between luteolin and inflammation were analyzed by Draw Venn diagram. Then the protein-protein interaction network of luteolin against inflammation was constructed to get core genes. Further, gene function and pathway enrichment analysis were performed. Finally, in vitro experiment was carried out to estimate the accuracy of predicted target genes. Results: ADME results indicated that luteolin has great potential to be developed into a drug. 226 overlapping targets (targets of luteolin against inflammation) were screened by matching 280 targets of luteolin with 9015 targets of inflammation. 9 core targets of luteolin against inflammation were identified, including MMP9, MAPK1, HSP90AA1, CASP3, ALB, EGFR, SRC, HRAS and ESR1. Gene function were mainly involved in metabolism, energy pathways and signal transduction. Pathway enrichment results suggested that metabolic pathways, pathways in cancer, PI3K-AKT signaling pathway, Ras signaling pathway and so on might be the critical pathways of luteolin against inflammation. RT-qPCR and ELISA results indicated that luteolin decreased the expression of most of core genes at protein and mRNA levels (MMP9, MAPK1, HSP90AA1, EGFR, SRC and HRAS). Conclusions: The anti-inflammatory mechanism of luteolin were systematically investigated based on network pharmacology, RT-qPCR and ELISA. Luteolin is expounded to have great potential to be developed into a drug and target various genes and pathways to perform systematic anti-inflammatory effect.

scholarly journals Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

2020 ◽  
Author(s):  
MengMeng Zhang ◽  
Dan Wang ◽  
Feng Lu ◽  
Rong Zhao ◽  
Xun Ye ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Cellular Response ◽  
Protein Localization ◽  
Docking Simulation ◽  
Estrogen Signaling ◽  
Receptor Protein ◽  
Network Pharmacology ◽  
Active Compounds

Abstract Background: Colon cancer is increasing recently but the high cost and adverse side effects experienced always leads to treatment drop out. Zingiber officinale, commonly known as ginger, is a popular herbal medicine and this study was aimed to identify the active compounds from ginger and to investigate its anti-cancer mechanisms through network pharmacology construction. Results: Ginger compounds were discerned through the TCMSP, which were filtered by the metrics of oral bioavailability and drug likeness, and its related targets were searched. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. Six potential active compounds, 288 interacting targets in addition to 1356 disease-related targets were collected, of which 114 intersection targets were obtained. The PPI network showed that 32 targets including SRC, PIK3R1, and TP53 were identified as key targets. These targets were mainly associated with the biological processes like transmembrane receptor protein tyrosine kinase signaling pathway, regulation of cellular protein localization, cellular response to oxidative stress. KEGG enrichment manifested that ginger probably produced preventive effects against colon cancer by regulating significant signaling pathway like pathway in cancer, hepatitis B, and estrogen signaling pathway. TP53, HSP90AA1, MAPK8, JAK2, CASP3, and ERBB2 could be viewed as the most potential target proteins, which were validated by molecular docking simulation.Conclusion: This study demonstrated the multi-component, multi-target, and multi-pathway characteristics of ginger, providing novel insight for ginger compounds developed as new drug for anti-colon cancer.

scholarly journals Anti-inflammatory activities of Sigesbeckia glabrescens Makino: combined in vitro and in silico investigations

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhangfeng Zhong ◽  
Qianru Zhang ◽  
Hongxun Tao ◽  
Wei Sang ◽  
Liao Cui ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Inflammatory Diseases ◽  
Chemical Constituents ◽  
Western Blots ◽  
Novel Approach ◽  
Inflammatory Mechanism ◽  
Mapk Signalling ◽  
Anti Inflammatory

Abstract Background Sigesbeckia glabrescens Makino (SG) is one of the important plant origins of Sigesbeckiae herba and has been widely used for the treatment of chronic inflammatory diseases in China. However, the underlying anti-inflammatory mechanism of SG is rarely investigated and reported. There are more than 40 kinds of chemical constituents in SG, but the action of the bioactive compounds of SG is still unclear. Therefore, we aimed to systemically investigate the mechanisms behind the anti-inflammatory properties of SG by combining in vitro and in silico investigations. Methods Cytotoxicity was measured using the 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Nitric oxide (NO) release was detected using the Griess assay. The secretion of pro-inflammatory cytokines and the expression of relevant proteins were assessed using ELISA kits and Western blots, respectively. Molecular docking was performed and scored using AutoDock via a comparison with the molecular docking of N-acetyl-d-glucosamine (NAG). Results In lipopolysaccharides (LPS)-stimulated macrophages, SG significantly inhibited NO, MCP-1, and IL-6 secretion; iNOS expression; and NF-κB activation but did not significantly affect MAPK signalling (p38, ERK, and JNK). Moreover, the results from the molecular docking prediction suggested that over 10 compounds in SG could likely target TLR4, p105, and p65. Conclusions These findings suggest that the anti-inflammatory effects of SG are highly related to the inactivation of NF-κB. Moreover, this study provides a novel approach to investigate the effects of herbal medicine using combined in vitro and in silico investigations.

scholarly journals Network Pharmacology-Based Identification of Potential Targets of Lonicerae japonicae Flos Acting on Anti-Inflammatory Effects

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Xiaoying Guo ◽  
Xiao Yu ◽  
Bingqing Zheng ◽  
Longfei Zhang ◽  
Fang Zhang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
Binding Activity ◽  
Network Pharmacology ◽  
Universal Method ◽  
Anti Inflammatory

Lonicerae japonicae flos (LJF) is widely used for the treatment of inflammation-related diseases in traditional Chinese medicine (TCM). To clarify the anti-inflammatory mechanism of LJF, 29 compounds with high content in LJF were selected for network pharmacology. Then, a comprehensive network pharmacology strategy was implemented, which involved compound-inflammation-target construction, protein-protein interaction (PPI) network analysis, and enrichment analysis. Finally, molecular docking and in vitro experiments were performed to verify the anti-inflammatory activity and targets of the key compound. As a result, 279 inflammation-associated proteins were identified, which are mainly involved in the AGE/RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and EGFR tyrosine kinase inhibitor resistance. A total of 12 compounds were linked to more than 35 targets, including apigenin, kaempferol, quercetin, luteolin, and ferulic acid. The results of molecular docking showed that AKT has the most binding activity, exhibiting certain binding activity with 10 compounds, including vanillic acid, protocatechuic acid, secologanic acid, quercetin, and luteolin; the results of qRT-PCR and WB confirmed that two key compounds, secologanic acid and luteolin, could significantly decrease the secretion of TNF-α and the AKT expression of RAW264.7 murine macrophages stimulated by LPS (lipopolysaccharide). These results demonstrate that the comprehensive strategy can serve as a universal method to illustrate the anti-inflammatory mechanisms of traditional Chinese medicine by identifying the pathways or targets.

scholarly journals An Investigation Into the Mechanism of Li Chong Pill for Treating Endometriosis Based on Network Pharmacology and Molecular Docking Verification

2021 ◽  
Author(s):  
Shao-Xuan Liu ◽  
Feng-Juan Han ◽  
Chun-Lan Zhang ◽  
Ying Shen ◽  
Jia Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Hormone Secretion ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Binding Activity ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Binding Property ◽  
Core Network

Abstract Background and objective: Li Chong Wan (Li Chong pill, LCP) origin from Yi Xue Zhong Zhong Can Xi Lu, (Records of Chinese Medicine with Reference to Western Medicine), widely used in the treatment of endometriosis (EM) in China. The purpose of this study is to investigate the intrinsic mechanisms of LCP against EM and to provide new evidence for its clinical application.Methods: Chemical compounds of LCP were screened and evaluated via retrieving public databases and literature. We also acquired their putative targets and obtained EM-related targets. The above-mentioned data were visualized as a component-target network. In addition, we use Cytoscape3.8.0 to build a protein-protein interaction network and identified hub genes and key active ingredients. Furthermore, through GO and KEGG pathway analyses, which were actualized by R3.6.1 (based on clusterProfiler, org.Hs.eg.Db, and pathview package), we obtained effective signaling pathways and biological functions. Molecular docking was used to verify binding activity between compounds and the key targets at last.Results: Finally, a total of 122 possible active targets and 47 components were screened. Identify the core network and screen out 10 main targets; GO and KEGG enrichment analysis revealed that LCP may have functions of anti-inflammatory, anti-angiogenesis, inhibition of cell proliferation, regulation of hormone secretion, etc. The effect of LCP on EM might be achieved by PI3K/Akt signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway, and VEGF signaling pathway, etc. Finally, molecular docking results demonstrated that 14 components were exhibited good binding property to the key targets of EM.Conclusion: This research ocularly demonstrated the multi-component, multi-target, and multi-channel pharmacological effects for LCP in the treatments of EM and provides evidence for further clinical research and verification of the mechanism.

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