Network Pharmacology and Molecular Docking-Based Analysis on Bioactive Anticoronary Heart Disease Compounds in Trichosanthes kirilowii Maxim and Bulbus allii Macrostemi

Trichosanthes kirilowii Maxim. and Bulbus allii Macrostemi are the components of Gualou Xiebai decoction (GLXB), a commonly used herbal combination for the treatment of coronary heart disease (CHD) in traditional Chinese medicine. Although GLXB is associated with a good clinical effect, its active compounds and mechanism of action remain unclear, which limits its clinical application and the development of novel drugs. In this study, we explored key compounds, targets, and mechanisms of action for GLXB in the treatment of CHD using the network pharmacology approach. We identified 18 compounds and 21 action targets via database screening. Enrichment analysis indicated that the effects of GLXB in patients with CHD are primarily associated with the regulation of signalling pathways for tumour necrosis factor, nuclear factor-kappa B, hypoxia-inducible factor-1, arachidonic acid metabolism, and insulin resistance. GLXB thus exerts anti-inflammatory, antihypoxic, and antiagglutinating effects; regulates lipid metabolism; and combats insulin resistance in CHD via these pathways, respectively. After reverse targeting, we observed that the main active compounds of GLXB in the treatment of CHD were quercetin, naringenin, β-sitosterol, ethyl linolenate, ethyl linoleate, and prostaglandin B1. To explore the potential of these compounds in the treatment of CHD, we verified the affinity of the compounds and targets via molecular docking analysis. Our study provides a bridge for the transformation of natural herbs and molecular compounds into novel drug therapies for CHD.

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

Scientific Reports ◽

10.1038/s41598-021-86914-8 ◽

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.

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Exploration of the mechanism of Ziyin Tongluo Formula on preventing and treating postmenopausal osteoporosis based on the network pharmacology and molecular docking

10.21203/rs.3.rs-39351/v2 ◽

2020 ◽

Author(s):

Rong-Bin Chen ◽

Ying-Dong Yang ◽

Kai Sun ◽

Shan Liu ◽

Wei Guo ◽

...

Keyword(s):

Molecular Docking ◽

Postmenopausal Osteoporosis ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Active Ingredients ◽

Active Compounds ◽

Core Proteins ◽

Key Genes

Abstract Background: Postmenopausal osteoporosis (PMOP) is a global chronic and metabolic bone disease, which poses huge challenges to individuals and society. Ziyin Tongluo Formula (ZYTLF) has been proved effective in the treatment of PMOP. However, the material basis and mechanism of ZYLTF against PMOP have not been thoroughly elucidated.Methods: Online databases were used to identify the active ingredients of ZYTLF and corresponding putative targets. Genes associated with PMOP were mined, and then mapped with the putative targets to obtain overlapping genes. Multiple networks were constructed and analyzed, from which the key genes were selected. The key genes were imported to the DAVID database to performs GO and KEGG pathway enrichment analysis. Finally, AutoDock Tools and other software were used for molecular docking of core compounds and key proteins. Results: Ninety-two active compounds of ZYTLF corresponded to 243 targets, with 129 target genes interacting with PMOP, and 50 key genes were selected. Network analysis showed the top 5 active ingredients including quercetin, kaempferol, luteolin, scutellarein, and formononetin., and the top 50 key genes such as VEGFA, MAPK8, AKT1, TNF, ESR1. Enrichment analysis uncovered two significant types of KEGG pathways in PMOP, hormone-related signaling pathways (estrogen , prolactin, and thyroid hormone signaling pathway) and inflammation-related pathways (TNF, PI3K-Akt, and MAPK signaling pathway). Moreover, molecular docking analysis verified that the main active compounds were tightly bound to the core proteins, further confirming the anti-PMOP effects. Conclusions: Based on network pharmacology and molecular docking technology, this study initially revealed the mechanisms of ZYTLF on PMOP, which involves multiple targets and multiple pathways.

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The Active Compounds of Yixin Ningshen Tablet and Their Potential Action Mechanism in Treating Coronary Heart Disease- A Network Pharmacology and Proteomics Approach

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4912395 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Xing Lv ◽

Huijun Wang ◽

Ruoming Wu ◽

Xiaoyan Shen ◽

Guan Ye

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Endocrine Resistance ◽

Arachidonic Acid Metabolism ◽

Network Pharmacology ◽

Active Components ◽

Literature Study ◽

Active Compounds ◽

Target Proteins ◽

Potential Target

Yixin Ningshen tablet is a CFDA-approved TCM formula for treating coronary heart disease (CHD) clinically. However, its active compounds and mechanism of action in treating CHD are unknown. In this study, a novel strategy with the combination of network pharmacology and proteomics was proposed to identify the active components of Yixin Ningshen tablet and the mechanism by which they treat CHD. With the application of network pharmacology, 62 active compounds in Yixin Ningshen tablet were screened out by text mining, and their 313 potential target proteins were identified by a tool in SwissTargetPrediction. These data were integrated with known CHD-related proteomics results to predict the most possible targets, which reduced the 313 potential target proteins to 218. The STRING database was retrieved to find the enriched pathways and related diseases of these target proteins, which indicated that the Calcium, MAPK, PI3K-Akt, cAMP, Rap1, AGE-RAGE, Relaxin, HIF-1, Prolactin, Sphingolipid, Estrogen, IL-17, Jak-STAT signaling pathway, necroptosis, arachidonic acid metabolism, insulin resistance, endocrine resistance, and steroid hormone biosynthesis might be the main pathways regulated by Yixin Ningshen tablet for the treatment of CHD. Through further enrichment analysis and literature study, EGFR, ERBB2, VGFR2, FGF1, ESR1, LOX15, PGH2, HMDH, ADRB1, and ADRB2 were selected and then validated to be the target proteins of Yixin Ningshen tablet by molecular docking, which indicated that Yixin Ningshen tablet might treat CHD mainly through promoting heart regeneration, new vessels’ formation, and the blood supply of the myocardial region and reducing cardiac output, oxygen demand, and inflammation as well as arteriosclerosis (promoting vasodilation and intraplaque neoangiogenesis, lowering blood lipid). This study is expected to benefit the clinical application of Yixin Ningshen tablet for the treatment of CHD.

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Pharmacological Mechanisms Underlying the Anti-asthmatic Effects of Modified Guomin Decoction Determined by Network Pharmacology and Molecular Docking

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.644561 ◽

2021 ◽

Vol 8 ◽

Author(s):

Guishu Wang ◽

Bo Zhou ◽

Zheyi Wang ◽

Yufeng Meng ◽

Yaqian Liu ◽

...

Keyword(s):

Molecular Docking ◽

Molecular Mechanism ◽

Airway Remodeling ◽

Enrichment Analysis ◽

Chronic Inflammatory Disease ◽

Network Pharmacology ◽

Active Components ◽

Active Compounds ◽

Protein Protein Interaction ◽

Pathway Annotation

BackgroundAsthma is a chronic inflammatory disease characterized by Th2-predominant inflammation and airway remodeling. Modified Guo Min decoction (MGMD) has been an extensive practical strategy for allergic disorders in China. Although its potential anti-asthmatic activity has been reported, the exact mechanism of action of MGMD in asthma remains unexplored.MethodsNetwork pharmacology approach was employed to predict the active components, potential targets, and molecular mechanism of MGMD for asthma treatment, including drug-likeness evaluation, oral bioavailability prediction, protein–protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Reactome pathway annotation. Molecular docking was carried out to investigate interactions between active compounds and potential targets.ResultsA total of 92 active compounds and 72 anti-asthma targets of MGMD were selected for analysis. The GO enrichment analysis results indicated that the anti-asthmatic targets of MGMD mainly participate in inflammatory and in airway remolding processes. The Reactome pathway analysis showed that MGMD prevents asthma mainly through regulation of the IL-4 and IL-13 signaling and the specialized pro-resolving mediators (SPMs) biosynthesis. Molecular docking results suggest that each bioactive compounds (quercetin, wogonin, luteolin, naringenin, and kaempferol) is capable to bind with STAT3, PTGS2, JUN, VEGFA, EGFR, and ALOX5.ConclusionThis study revealed the active ingredients and potential molecular mechanism by which MGMD treatment is effective against airway inflammation and remodeling in asthma through regulating IL-4 and IL-13 signaling and SPMs biosynthesis.

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Molecular Mechanism of Danxiong Tongmai Granules in Treatment of Coronary Heart Disease

10.21203/rs.3.rs-784340/v1 ◽

2021 ◽

Author(s):

Jiahao Ye ◽

Ruiping Yang ◽

Zhixi Hu ◽

Lin Li ◽

Senjie Zhong ◽

...

Keyword(s):

Molecular Dynamics ◽

Coronary Heart Disease ◽

Heart Disease ◽

Molecular Docking ◽

Enrichment Analysis ◽

Dynamics Simulation ◽

Venn Diagram ◽

Network Pharmacology ◽

Ppi Network ◽

Ligand Interaction

Abstract Background: Network pharmacology has been widely adopted for mechanistic studies of Traditional Chinese Medicines (TCM). The present study uses network pharmacology to investigate the main ingredients, targets and pathways of Danxiong Tongmai Granules (DXTMG) in the treatment of coronary heart disease (CHD). We aim to validate our findings using molecular docking and molecular dynamics simulations.Methods: TCM compounds and targets were identified via searches in the BATMAN-TCM database, and the GeneCards database were used to obtain the main target genes involved in CHD, We combined disease targets with the drug targets to identify common targets, and draw a Venn diagram to visualize the results. The "TCM-compound-target" network was plotted using Cytoscape 3.7.2 software and a protein-protein interaction (PPI) network was constructed using the STRING database from which core targets were obtained. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for common drug-disease targets using R Version 4.0.4 (64 bit) software. Molecular docking of core protein-small molecule ligand interaction was modeled using AutoDock Vina software. A simulation of molecular dynamics was conducted for the optimal protein-ligand complex obtained by molecular docking using Amber18 software.Results: 162 potential targets of DXTMG involved in CHD were identified. These included INS, ALB, IL-6 and TNF according to PPI network studies. GO enrichment analysis identified a total of 3365 GO pathways, including 3049 biological process pathways (BP) concerned with the heart and circulatory system;109 cellular component (CC) pathways, including cation channels and membrane rafts and 207 molecular function (MF) pathways related to receptor ligands and activators. KEGG analysis revealed a total of 137 pathways (p<0.05), including those related to AGE-RAGE signaling associated with diabetic complications, fluid shear stress and atherosclerosis. Molecular docking revealed the highest binding energy for Neocryptotanshinone Ii (the key compound of DXTMG) and TNF. Molecular dynamics simulation indicated stable binding for TNF-Neocryptotanshinone Ii with strong hydrophobic interactions mediated predominantly by the hydrophobic residues, Leu279, Val280 and Phe278 plus hydrogen-bonding with Leu279.Conclusion: The present study reveals novel insights into the mechanism of DXTMG in treating CHD. DXTMG can influence oxidative stress、inflammation response and regulating cardiomyocytes, thereby reducing the occurrence and development of CHD.

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Exploring the Pharmacological Mechanism of Duhuo Jisheng Decoction in Treating Osteoporosis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5510290 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Zhencheng Xiong ◽

Can Zheng ◽

Yanan Chang ◽

Kuankuan Liu ◽

Li Shu ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Active Compounds ◽

Treatment Of Osteoporosis ◽

Target Proteins

Objective. The purpose of this work is to study the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of osteoporosis based on the methods of bioinformatics and network pharmacology. Methods. In this study, the active compounds of each medicinal ingredient of DHJSD and their corresponding targets were obtained from TCMSP database. Osteoporosis was treated as search query in GeneCards, MalaCards, DisGeNET, Therapeutic Target Database (TTD), Comparative Toxicogenomics Database (CTD), and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and osteoporosis were identified, and then GO and KEGG enrichment analysis were performed. Cytoscape was employed to construct DHJSD-compounds-target genes-osteoporosis network and protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. The activities of binding of hub genes and key components were confirmed by molecular docking. Results. 174 active compounds and their 205 related potential targets were identified in DHJSD for the treatment of osteoporosis, including 10 hub genes (AKT1, ALB, IL6, MAPK3, VEGFA, JUN, CASP3, EGFR, MYC, and EGF). Pathway enrichment analysis of target proteins indicated that osteoclast differentiation, AGE-RAGE signaling pathway in diabetic complications, Wnt signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, calcium signaling pathway, and TNF signaling pathway were the specifically major pathways regulated by DHJSD against osteoporosis. Further verification based on molecular docking results showed that the small molecule compounds (Quercetin, Kaempferol, Beta-sitosterol, Beta-carotene, and Formononetin) contained in DHJSD generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes. Conclusion. This study reveals the characteristics of multi-component, multi-target, and multi-pathway of DHJSD against osteoporosis and provides novel insights for verifying the mechanism of DHJSD in the treatment of osteoporosis.

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Exploring Molecular Mechanism of Traditional Chinese Medicine Euphorbiae Semen on Reversing of Multidrug Resistance in Leukemia Based on Network Pharmacology Strategy and Molecular Docking Technology

10.21203/rs.3.rs-55927/v1 ◽

2020 ◽

Author(s):

Xiao Song ◽

Fei Guo ◽

Xiao-Chen Sun ◽

Shu-Yue Wang ◽

Yao-Hui Yuan ◽

...

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Biological Functions ◽

Active Compounds ◽

The Core ◽

The World ◽

Target Network ◽

Compound Target

Abstract Background: Leukemia was listed by the World Health Organization as one of the five most intractable diseases in the world. The multi-drug resistance (MDR) of leukemia cells limits the efficacy of anti-tumor drugs and is the major reason for the chemotherapy failure and recurrence of leukemia chemotherapy. Some studies have shown that Euphorbiae semen (ES) possesses the characteristics of new therapeutic drugs for MDR. However, the molecular mechanisms and active compounds have not yet been fully clarified. Therefore, there is a need for explore its active compounds and demonstrate its mechanisms through network pharmacology and molecular docking technology.Method: First, the TCMSP database was searched and screened the active compounds of the ES, supplemented with compounds verified by literature, so as to further identify the core compounds in the active ingredient. Simultaneously, the TCMSP and Swiss database were searched to the targets of active compounds, and the targets of reverses leukemia multidrug resistance (RL-MDR) were screened in the relevant databases, such as GeneCards and DrugBank. Then, the targets of active compounds were intersected with RL-MDR targets to obtain potential targets of ES acting on MDR. The compound–target network was constructed by Cytoscape. The target protein–protein interaction network was built using STRING and Cytoscape database. Second, the R language and DAVID database were used to analyse Gene Ontology (GO) biological functions analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways enrichment. Finally, molecular docking method was utilized to investigate the binding activity between the core targets and the active compounds of ES.Results: Compound–target network mainly contained 22 compounds and 81 corresponding targets. Finally, seven components in ES were selected and 10 core targets were identified; Key targets contained JUN, CASP3, MAOA, AR, PPARG, DRD2, ADRA2A, CHRM2, PTGS2 and MAPK14. GO enrichment analysis indicated the main biological functions of potential genes of ES in the treatment of MDR. KEGG pathway enrichment analysis showed the main pathways, mainly including apoptosis, pathways in cancer, p53 signaling pathway, VEGF signaling pathway, TNF signaling pathway and PI3K–Akt signaling pathway. Finally, we chose the top 10 common targets for molecular docking with the 7 active compounds of ES. The results of molecular docking indicated that the compounds of ES, which had good affinity with targets. Conclusion: The molecular mechanism of ES in the treatment of MDR showed the synergistic reaction of multi-compound, multi-target, and multi-pathway of traditional Chinese medicine, which provided ideas for further clinical research.

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Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

10.21203/rs.3.rs-41447/v1 ◽

2020 ◽

Author(s):

Wanjin Fu ◽

Ajuan Gong ◽

Bin Yu ◽

Xin Wei ◽

Yong Chen ◽

...

Keyword(s):

Lung Cancer ◽

Molecular Docking ◽

Small Cell Lung Cancer ◽

Active Compound ◽

Enrichment Analysis ◽

Small Cell ◽

Network Pharmacology ◽

Small Cell Lung ◽

Active Compounds

Abstract Background: Shenlian Capsule is a Chinese medicine compound approved by the China Food and Drug Administration (CFDA) for the treatment of advanced non-small cell lung cancer(NSCLC). However, due to its complex constituents, cause its effective active compounds and main action mechanisms for treating diseases are still not fully clear. The purpose of this work is to explore the active ingredients and mechanisms of Shenlian Capsule treatment NSCLC through a system pharmacological approach. Methods: First, a database of Shenlian Capsule chemical composition was constructed by retrieving Chinese herbal medicine data. Absorption, distribution, metabolism and excretion (ADME) methods were used to screen potential active compounds. Predict active compound targets with a large-scale molecular network target prediction technology. Clustering of active compounds obtained through cluster analysis by MECODE plug-in, each cluster obtains the main pathways through enrichment analysis method. To get all targets related to survival in NSCLC, the survival related targets were intersected with the compounds target (C-T) network to get the survival related targets for Shenlian Capsule. Finally, a batch molecular docking technique was used to verify the effect of active compounds of Shenlian Capsule on survival-related targets.Results: The Shenlian Capsule C-T network was constructed with 117 potential compounds and 47 targets. Treatment of NSCLC with Shenlian Capsule through enrichment analysis may involve multiple pathways such as anti-inflammatory, immune regulation, regulation of cell cycle, apoptosis, antiviral, cell hypoxia, angiogenesis and so on. Shenlian Capsule has eight survival-related genes in non-small cell lung adenocarcinoma (LUAD) and two survival-related genes in non-small cell squamous cell lung carcinoma (LUSC). It is known through molecular docking that the active compound has lower energy after conformation with survival-related genes, and has lower binding energy and stable binding.Conclusion: In this study, the potential compounds of active compounds in Shenlian Capsule were first predicted using network pharmacology technology. Through the enrichment analysis, the main pathways of the role of Shenlian Capsule were outcropped. Secondly, by combining bioinformatics and network pharmacology, Shenlian Capsule can be regulated to target survival-related targets. Finally, the molecular docking technique shows the relationship between active compounds and survival-related targets after docking. This work provided a scientific basis for the clinical role of Shenlian Capsule in the treatment of NSCLC, provided a research basis for further clarifying the active ingredients and mechanism of Shenlian Capsule in the treatment of NSCLC.

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Systematic evaluation of the mechanisms of Mulberry leaf (Morus alba Linne) acting on diabetes based on network pharmacology and molecular docking

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200914103719 ◽

2020 ◽

Vol 23 ◽

Author(s):

Qiguo Wu ◽

Yeqing Hu

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Active Compounds ◽

Pathway Network ◽

Pathway Enrichment ◽

Mulberry Leaves ◽

Mulberry Leaf

Background: Diabetes mellitus is one of the most common endocrine metabolic disorder diseases. The application of herbal medicine to control glucose levels and improve insulin action might be a useful approach in the treatment of diabetes. Mulberry leaves (ML) has been reported to exert important activities of anti-diabetic. Objective: In this work, we aimed to explore the multi-targets and multi-pathways regulatory molecular mechanism of Mulberry leaves (ML, Morus alba Linne) acting on diabetes. Methods: Identification of active compounds of Mulberry leaves using Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Bioactive components were screened by FAF-Drugs4 website (Free ADME-Tox Filtering Tool). The targets of bioactive components were predicted from SwissTargetPrediction website, and the diabetes related targets were screened from GeneCards database. The common targets of ML and diabetes are used for Gene Ontology (GO) and pathway enrichment analysis. The visualization networks were constructed by Cytoscape 3.7.1 software. The construction of biological networks were performed to analyze the mechanisms as follows: (1) Compound-Target network; (2) Common target-Compound network; (3) Common targets protein interaction network; (4) Compound-Diabetes protein-protein interactions (PPI) network; (5) Target-Pathway network; (6) Compound-Target-Pathway network. At last, the prediction results of network pharmacology were verified by molecular docking method. Results: 17 active components were obtained by TCMSP database and FAF-Drugs4 website. 51 potential targets (11 common targets and 40 associated indirect targets) were obtained and used to build the PPI network by String database. Furthermore, the potential targets were used to GO and pathway enrichment analysis. 8 key active compounds (quercetin, Iristectorigenin A, 4-Prenylresveratrol, Moracin H, Moracin C, Isoramanone, Moracin E and Moracin D) and 8 key targets (AKT1, IGF1R, EIF2AK3, PPARG, AGTR1, PPARA, PTPN1 and PIK3R1) were obtained to play major roles in Mulberry leaf acting on diabetes. And the signal pathways involved in the mechanisms mainly include AMPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, insulin signaling pathway and insulin resistance. The molecular docking results show that the 8 key active compounds have good affinity with the key target of AKT1, and the 5 key targets (IGF1R, EIF2AK3, PPARG, PPARA and PTPN1) have better affinity than AKT1 with the key compound of quercetin. Conclusion: Based on network pharmacology and molecular docking of this work provided an important systematic and visualized basis for further understanding the synergy mechanism of ML acting on diabetes.

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Network pharmacology and molecular docking approaches to investigating the mechanism of action of Zanthoxylum bungeanum in the treatment of oxidative stress-induced diseases

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999201117112316 ◽

2020 ◽

Vol 23 ◽

Author(s):

Rong Zhao ◽

Meng-Meng Zhang ◽

Dan Wang ◽

Wei Peng ◽

Qing Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Docking ◽

Signaling Pathways ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Network Pharmacology ◽

Therapeutic Effects ◽

Active Components ◽

Active Compounds ◽

Zanthoxylum Bungeanum

Background: Zanthoxylum bungeanum Maxim., a traditional Chinese herbal medicine, has been reported to possess therapeutic effects on diseases induced by oxidative stress (DOS), such as atherosclerosis and diabetes complication. However, the active components and its related mechanisms are still not systematically reported. Objective: The current study was aimed to explore the main active ingredients and its molecular mechanisms of Z. bungeanum for treating DOS using network pharmacology combined with molecular docking simulation. Methods: The active components of Z. bungeanum pericarps, in addition to the interacting targets, were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. These components were filtered using the parameters of oral bioavailability and drug-likeness, and the targets related to DOS were obtained from the Genecards and OMIM database. Furthermore, the overlapping genes were obtained, and a protein-protein interaction was visualized using the STRING database. Next, the Cytoscape software was employed to build a disease/drug/component/target network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R software. Finally, the potential active compounds and their related targets were validated using molecular docking technology. Results: A total of 61 active compounds, 280 intersection genes, and 105 signaling pathways were obtained. Functional enrichment analysis suggested that DOS occurs possibly through the regulation of many biological pathways, such as AGERAGE and HIF-1 signaling pathways. Thirty of the identical target genes showed obvious compact relationships with others in the STRING analysis. Three active compounds, quercetin, diosmetin, and beta-sitosterol, interacting with the four key targets, exhibited strong affinities. Conclusion: The findings of this study not only indicate the main mechanisms involving in the oxidative stress-induced diseases, but also provide the basis for further research on the active components of Z. bungeanum for treating DOS.

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