Mechanistic Investigation of Glycyrrhiza uralensis Effects against Respiratory Ailments: Application of Network Pharmacology and Molecular Docking Approaches

Background: Glycyrrhiza uralensis, also known as liquorice, is a herbal remedy that is traditionally used worldwide for treating respiratory ailments and ameliorating breathing. Objective: The objective of this systematic study was to investigate active ingredients of Glycyrrhiza uralensis and determine its mode of action in silico against severe and acute respiratory complications of respiratory ailments through network pharmacology and molecular docking studies. Methods: TCMSP database search helped retrieve the compounds of Glycyrrhiza uralensis and their protein targets, especially related to respiratory ailments. Subsequently, the protein-protein association was attained as a network by using the STITCH database. Cytoscape and its ClueGO plugin were used to study gene ontology (GO) enrichment. In addition, seven natural compounds were docked in the active site of four different molecular targets; JUN-FOS, COX2, MAPK14 and IL-6, to identify the binding mechanism of ligands under study. Results: TCMSP database search resulted in the retrieval of 280 compounds of Glycyrrhiza uralensis (including formononetin, naringenin, sitosterol, isorhamnetin, kaempferol, quercetin and Glycyrrhizin) and 135 protein targets. A careful study of targets showed that 26 prospective targets (including JUN, FOS, IL6, MAPK14 and PTGS2) related to respiratory ailments were identified. Gene ontology (GO) enrichment analysis resulted in the retrieval of 176 GO terms, which were associated with respiratory ailments. This study proposed that Glycyrrhiza uralensis acts against respiratory ailments through various proteins, such as JUN, FOS, IL6, MAPK14 and PTGS2. Docking results revealed that among all studied ligands, the flavonoid-based compounds isorhamnetin and kaempferol form stronger complexes with JUN-FOS-DNA, MAPK-14, and IL-6 proteins (Cscore=6.81, 4.27, and 4.77, respectively) and the saponin based compound glycyrrhizin (Cscore=13.07) demonstrated stronger binding affinity towards COX2 enzyme. Conclusion: Conclusively, isorhamnetin, kaempferol and glycyrrhizin in Glycyrrhiza uralensis may regulate several signaling pathways through JUN-FOS-DNA, MAPK-14, and IL-6, which might play a therapeutic role against respiratory ailments.

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Molecular docking and network connections of active compounds from the classical herbal formula Ding Chuan Tang

PeerJ ◽

10.7717/peerj.8685 ◽

2020 ◽

Vol 8 ◽

pp. e8685

Author(s):

Allison Clyne ◽

Liping Yang ◽

Ming Yang ◽

Brian May ◽

Angela Wei Hong Yang

Keyword(s):

Molecular Docking ◽

Song Dynasty ◽

Network Pharmacology ◽

Herbal Formula ◽

Protein Targets ◽

The Song Dynasty ◽

Network Connections ◽

Asthma Drug ◽

Cellular Pathways ◽

Disease Pathways

Background Ding Chuan Tang (DCT), a traditional Chinese herbal formula, has been consistently prescribed for the therapeutic management of wheezing and asthma-related indications since the Song Dynasty (960–1279 AD). This study aimed to identify molecular network pharmacology connections to understand the biological asthma-linked mechanisms of action of DCT and potentially identify novel avenues for asthma drug development. Methods Employing molecular docking (AutoDock Vina) and computational analysis (Cytoscape 3.6.0) strategies for DCT compounds permitted examination of docking connections for proteins that were targets of DCT compounds and asthma genes. These identified protein targets were further analyzed to establish and interpret network connections associated with asthma disease pathways. Results A total of 396 DCT compounds and 234 asthma genes were identified through database search. Computational molecular docking of DCT compounds identified five proteins (ESR1, KDR, LTA4H, PDE4D and PPARG) mutually targeted by asthma genes and DCT compounds and 155 docking connections associated with cellular pathways involved in the biological mechanisms of asthma. Conclusions DCT compounds directly target biological pathways connected with the pathogenesis of asthma including inflammatory and metabolic signaling pathways.

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Anti-inflammatory Properties of Fangji Huangqi Tang: Discovery Based on Network Pharmacology, Molecular Docking and Arrowsmith Tools

10.21203/rs.3.rs-242873/v1 ◽

2021 ◽

Author(s):

Qingtao Jiang ◽

Lei Han ◽

Xin Liu ◽

Feng Zhang

Keyword(s):

Gene Ontology ◽

Molecular Docking ◽

Signaling Pathways ◽

Tight Binding ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Classical Formula ◽

Anti Inflammatory ◽

Principal Elements ◽

Compound Target

Abstract Fangji Huangqi Tang (FHT) is a classical formula widely used in Chinese clinical practice. In this study, a creative application of FHT for inflammation has been identified by network pharmacology-based framework. Specifically, a total of 17 bioactive compounds including 42 potential targets of FHT, and 205 related targets involved in inflammation were retrieved from mainstream databases and subjected to network analysis. 13 intersection targets indicated the principal elements linked to inflammation therapy. Top terms of Gene Ontology (GO) analysis were identified, while 7 related signaling pathways were revealed by Kyoto Encyclopedia of Genes and Genomes (KEGG) results. Subsequently, Calycosin-PTGS2 with tight binding affinity (BA) was manifested by molecular docking as the critical compound-target couple. Meaningful links between Calycosin and inflammation were implied through Arrowsmith, which overlapped with the findings in enrichment analysis, such as MAPK, NF-κB that could be regulators of PTGS2. In summary, the present study explored the potential targets and signaling pathways of FHT against inflammation, which may help to illustrate the mechanisms responsible for the action of FHT and provide a better understanding of its anti-inflammatory effects.

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Uncovering the Pharmacological Mechanism of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Against Lung Cancer Based on Network Pharmacology and Experimental Evaluation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.617555 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lihui Wang ◽

Xin Yang ◽

Qiong Song ◽

Jiejun Fu ◽

Wenchu Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Gene Ontology ◽

Survival Analysis ◽

Molecular Docking ◽

Therapeutic Potential ◽

Therapeutic Targets ◽

Network Pharmacology ◽

Lung Cancer Cell ◽

Pharmacological Mechanism

Background: 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1,4-Dione (DMDD) was purified from the roots of Averrhoa carambola L. Previous research demonstrated that DMDD is a small molecular compound with significant therapeutic potential for tumors. However, the potential targets and pharmacological mechanism of DMDD to treat lung cancer has not been reported.Methods: We employed network pharmacology and experimental evaluation to reveal the pharmacological mechanism of DMDD against lung cancer. Potential therapeutic targets of DMDD were screened by PharmMapper. Differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA) lung cancer data sets were extracted and analyzed by GEPIA2. The mechanism of DMDD against lung cancer was determined by PPI, gene ontology (GO) and KEGG pathway enrichment analysis. Survival analysis and molecular docking were employed to obtain the key targets of DMDD. Human lung cancer cell lines H1975 and PC9 were used to detect effects of DMDD treatment in vitro. The expression of key targets after DMDD treated was validated by Western Blot.Results: A total of 60 Homo sapiens potential therapeutic targets of DMDD and 3,545 DEGs in TCGA lung cancer datasets were identified. Gene ontology and pathway analysis revealed characteristic of the potential targets of DMDD and DEGs in lung cancer respectively. Cell cycle and pathways in cancer were overlapping with DMDD potential targets and lung cancer DEGs. Eight overlapping genes were found between DMDD potential therapeutic targets and lung cancer related DEGs. Survival analysis showed that high expression of DMDD potential targets CCNE1 and E2F1 was significantly related to poor patient survival in lung cancer. Molecular docking found that DMDD exhibited significant binding affinities within the active site of CCNE1 and E2F1. Further tests showed that DMDD inhibited the proliferation, migration and clone formation in lung cancer cell lines (H1975 and PC9) in a dose and time dependent manner. Mechanistically, DMDD treatment decreased the expression of CDK2, CCNE1, E2F1 proteins and induced cell cycle arrest at the G1/S phase in H1975 and PC9 cells.Conclusion: These results delineated that DMDD holds therapeutic potential that blocks tumorigenesis by cell cycle regulation in lung cancer, and may provide potential therapies for lung cancer.

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Network Pharmacology Study and Molecular Docking on the Mechanism of Treatment of Colorectal Cancer by Xiao-Chai-Hu-Tang

10.21203/rs.3.rs-157805/v1 ◽

2021 ◽

Author(s):

Jingyun Jin ◽

Bin Chen ◽

Xiangyang Zhan ◽

Zhiyi Zhou ◽

Hui Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Gene Ontology ◽

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Signal Pathways ◽

Active Ingredients ◽

Pathway Gene

Abstract Background and objective: To predict the targets and signal pathways of Xiao-Chai-Hu-Tang (XCHT) in the treatment of colorectal cancer (CRC) based on network pharmacology, to further analyze its anti-CRC material basis and mechanism of action.Methods: TCMSP and TCMID databases were adopted 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 above common targets were used to construct the “herb-active ingredients-target” network by Cytoscape 3.8.0 software. And then, the protein-to-protein interaction（PPI）was constructed and analyzed with BisoGenet and CytoNCA plug-in in Cytoscape. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were then performed using the R package of cluster Profiler. Further, AutoDock Vina software was used to conduct molecular docking studies on the active ingredients and key targets to verify the network pharmacological analysis results.Results: A total of 71 active ingredients of XCHT and 20 potential targets for anti-CRC were identified. The network analysis revealed that quercetin, stigmasterol, kaempferol, baicalein, acacetin may be the key compounds. And PTGS2, NR3C2, CA2, MMP1 may be the key targets. The active ingredients of XCHT interacted with most disease targets of CRC. It fully showed that XCHT exerted its therapeutic effect through the synergistic action of the multi-compound, multi-target, and multi-pathway. Gene ontology enrichment analysis showed 46 GO entries, including 20 biological processes, 6 cellular components, and 20 molecular functions. 11 KEGG signaling pathways had been identified, including IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and NF-kappa B signaling pathway. It showed that XCHT played a role in the treatment of CRC by regulating different signal pathways. Molecular docking confirmed the correlation between five core compounds (including quercetin, stigmasterol, kaempferol, baicalein, and acacetin) and PTGS2.Conclusion: The potential active ingredients, possible targets, and key biological pathways for the efficacy of XCHT in the treatment of CRC were preliminarily described, which provided a theoretical basis for further experimental verification research.

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Identification of Potential Bioactive Ingredients and Mechanisms of the Guanxin Suhe Pill on Angina Pectoris by Integrating Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/4280482 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Mingmin Wang ◽

Shuangjie Yang ◽

Mingyan Shao ◽

Qian Zhang ◽

Xiaoping Wang ◽

...

Keyword(s):

Molecular Docking ◽

Angina Pectoris ◽

Protein Interaction ◽

Interaction Analysis ◽

Network Pharmacology ◽

Biological Processes ◽

Protein Protein Interaction ◽

Go Enrichment ◽

Chemokine Ligand ◽

Bioactive Ingredients

The Guanxin Suhe pill (GSP), a traditional Chinese medicine, has been widely used to treat angina pectoris (AP) in Chinese clinical practice. However, research on the bioactive ingredients and underlying mechanisms of GSP in AP remains scarce. In this study, a system pharmacology approach integrating gastrointestinal absorption (GA) evaluation, drug-likeness (DL) evaluation, target exploration, protein-protein-interaction analysis, Gene Ontology (GO) enrichment analysis, network construction, and molecular docking was adopted to explore its potential mechanisms. A total of 481 ingredients from five herbs were collected, and 242 were qualified based on GA and DL evaluation. Target exploration identified 107 shared targets between GSP and AP. Protein-protein interaction identified VEGFA (vascular endothelial growth factor A), TNF (tumor necrosis factor), CCL2 (C-C motif chemokine ligand 2), FN1 (fibronectin 1), MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), IL10 (interleukin 10), CXCL8 (C-X-C motif chemokine ligand 8), IL6 (interleukin 6), and INS (insulin) as hub targets for GSP, which were involved in the inflammatory process, ECM proteolysis, glucose metabolism, and lipid metabolism. GO enrichment identified top pathways in the biological processes, molecular functions, and cell components, explaining GSP’s potential AP treatment mechanism. Positive regulation of the nitric oxide biosynthetic process and the response to hypoxia ranked highest of the biological processes; core targets that GSP can regulate in these two pathways were PTGS2 and NOS2, respectively. Molecular docking verified the interactions between the core genes in the pathway and the active ingredients. The study lays a foundation for further experimental research and clinical application.

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New perspective: the multi-targets mechanism of hydroxychloroquine in the treatment of rheumatoid arthritis based on network pharmacology

10.21203/rs.3.rs-65359/v1 ◽

2020 ◽

Author(s):

Bo Xie ◽

Haojie Lu ◽

Jinhui Xu ◽

Yebei Hu ◽

Haixin Luo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Drug Targets ◽

Cell Activation ◽

Acid Amide ◽

Network Pharmacology ◽

Protein Targets ◽

Protein Protein Interaction ◽

Amide Hydrolase ◽

New Perspective

Abstract Background Network pharmacology is a new method of bioinformatics in exploring drug targets in recent 3 years. Hydroxychloroquine (HCQ) is a multi-targets drug that are clinically effective in rheumatoid arthritis (RA) but whose mechanism is not well understood. Methods The predicted targets of HCQ and the proteins related to RA were returned from databases. Followed by protein-protein interaction (PPI) network, the intersection of the two group of proteins was conducted. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was used to analyse these proteins in a macro perspective. Finally, the candidate targets were verified by molecular docking. Results The results suggest that the efficacy of HCQ against RA is mainly associated with 4 targets of smoothened homolog (SMO), sphingosine kinase (SPHK) 1, SPHK2 and gatty-acid amide hydrolase (FAAH), with their related 3316 proteins’ network which regulate ErbB, HIF-1, NF-κB, FoxO, Chemokine, MAPK, PI3K/Akt pathways and so forth. Biological process are mainly concentrated in the regulation of cell activation, myeloid leukocyte activation, regulated exocytosis and so forth. Molecular docking analysis shows that hydrogen bonding and π-π stacking are the main forms of chemical force. Conclusions Our research provides protein targets affected by HCQ in the treatment of RA. SMO, SPHK1, SPHK2 and FAAH involving 3316 proteins become the multi-targets mechanism of HCQ in the treatment of RA. As well, the research also provides a new idea for introducing network pharmacology into the evaluation of the multi-target drugs in internal medicine.

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Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Angelicae Pubescentis Radix in the treatment of rheumatoid arthritis

10.21203/rs.3.rs-445750/v1 ◽

2021 ◽

Author(s):

yanni yang ◽

yirixiati aihaiti ◽

peng xu ◽

haishi zheng

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Receptor Interaction ◽

Active Components ◽

Target Proteins ◽

Go Enrichment ◽

Go Enrichment Analysis

Abstract Purpose:To explore the potential target proteins underlying the effect of Angelicae Pubescentis Radix(APR) on rheumatoid arthritis (RA) using a network pharmacology and molecular docking approach .Methods:First, the active components and target proteins of APR and RA related disease targets were obtained from the TCMSP, Gene Card,OMIM,DisGeNET and STRING databases. Then the active ingredient target in the RA network diagram was drawn using Cytoscape 3.7.1 software. Protein-protein interaction analysis, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were carried out using the STRING and David databases. The crystal structures of RA related targets were retrieved from the RCSB PDB database. Finally, the potential active compounds and their related targets were validated using molecular docking technology.Results: Five active components of Angelicae Pubescentis Radix(APR) were screened out, including ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone and 80 key targets including MAPK8,EGFR,PTGS2,CASPASE3,MTOR,SRC,KDR,MAPK1,NOS3 and MAPK14, etc were obtained. GO enrichment analysis showed that 222 biological processes, 34 cell components and 72 molecular functions were identified; KEGG analysis showed that the targets of APR in the treatment of RA were significantly enriched in pathways in cancer, the PI3K−Akt signaling pathway, Proteoglycans in cancer, osteoclast differentiation, neuroactive ligand−receptor interaction, tuberculosis,TNF signaling pathway, serotonergic synapse, Rap1 signaling pathway,cAMP signaling pathway. The results of molecular docking showed that ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone had strong affinity for PTGS2, EGFR and MAPK8.Conclusion: APR treats RA through the characteristics of multi-component, multi-target and multi-pathway regulation.

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Study on the Antianxiety Mechanism of Suanzaoren Decoction Based on Network Pharmacology and Molecular Docking

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5531136 ◽

2021 ◽

Vol 2021 ◽

pp. 1-28

Author(s):

Xiaocong Xu ◽

Bingbing Gao ◽

Xiongying Li ◽

Shanshan Lei

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Interaction Analysis ◽

Modern Medicine ◽

Network Pharmacology ◽

Active Components ◽

Material Basis ◽

Go Enrichment ◽

Antianxiety Drug ◽

Analysis Platform

Objective. Suanzaoren Decoction (SZRT) is a classic decoction to calm the nerves in traditional Chinese medicine (TCM). It has been extensively treated as an antianxiety drug in modern times, but the material basis and pharmacological mechanisms are still unclear. To explore the material basis and corresponding potential targets, as well as to elucidate the mechanism of SZRT, network pharmacology and molecular docking methods were utilized. Methods. The main chemical compounds and potential targets of SZRT were collected from the pharmacological database analysis platform (TCMSP). Anxiety targets were obtained from the GeneCards database. Then, a target compound network was established using overlapping genes and the corresponding potential compounds. Protein interaction analysis, GO enrichment, and KEGG pathway enrichment were performed using the STRING database, DAVID database, and KOBAS database. Finally, molecular docking was conducted between MAOB and its corresponding active compound in SZRT to further verify the results. Results. A total of 137 active components in SZRT were screened from the TCMSP database, and 210 corresponding targets were predicted. A total of 5434 anxiety-related targets were obtained from the disease target database, and finally 22 potential targets of SZRT on antianxiety were obtained. The constructed C-T network showed that the average degree of active components was 5.4, and four of them interacted with six or more targets. PPI analysis shows that key genes such as MAOA, MAOB, IL1B, TNF, NR3CI, and HTR3A were identified as potential therapeutic targets. A pathway analysis showed that SZRT may participate in neurotransmitter regulation and immunoregulation in a synergistic way to treat anxiety. The binding energy between the active compounds and MAOB was low, indicating good binding. The results of molecular docking showed that all the 10 active ingredients were able to successfully dock with MAOB, and the binding energy of coumaroyltyramine with MAOB was the lowest, that is, −9.6 kcal/mol, and the binding method was hydrogen bonding. Conclusions. SZRT produces antianxiety effects mainly by affecting the neurotransmitter release, transmission, and immunoregulation. This study provides a new approach to elucidating the molecular mechanism and material basis of SZRT in the treatment of anxiety, and it will also benefit the application of TCM in modern medicine.

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Exploration of underlying molecular mechanism of Lycii Cortex in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

E3S Web of Conferences ◽

10.1051/e3sconf/202123302007 ◽

2021 ◽

Vol 233 ◽

pp. 02007

Author(s):

Dongjun Li ◽

Denghui Wang ◽

Shikai Yan

Keyword(s):

Molecular Docking ◽

Signaling Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Kegg Pathway Analysis ◽

Go Enrichment ◽

Core Components ◽

Receptor Signaling Pathway ◽

Go Enrichment Analysis

Objective: To explore the potential molecular mechanism of Lycii Cortex in treating type 2 diabetes mellitus (T2DM) by virtue of network pharmacology and molecular docking method. Methods: Ingredients of Lycii Cortex were collected from TCMSP and BATMAN-TCM databases, and the corresponding targets and T2DM-related targets were obtained respectively from SwissTargetPrediction and GenCards databases. Venn diagram was applied to derive the potential active components and effect targets of Lycii Cortex in the treatment of T2DM. GO enrichment analysis and KEGG pathway analysis were performed in the database of DAVID. Cytoscape 3.6.1 was used to produce the “core components-core targets” network. The molecular docking between core components and core targets was implemented through Autodock Vina. Results: Six core components and twelve core targets of Lycii Cortex in treating T2DM were identified. GO enrichment analysis and KEGG pathway analysis suggested the following signaling pathways and biological processes were involved in the treatment of T2DM by Lycii Cortex: PI3K-Akt signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and peptidyl-threonine phosphorylation, the positive regulation of cyclase activity, the positive regulation of genetic expression, and lipoprotein translocation. The binding results demonstrated a relatively high affinity between core components of Lycii Cortex, including kulactone, hederagenin, scopolin, etc., and core targets, containing IL6, PPARγ, TNF, and mTOR, indicating the efficacy of Lycii Cortex in treating T2DM. Conclusion: Lycii Cortex plays a role in the treatment of T2DM with its ingredients such as kulactone, linarin, hederagenin, and scopolin regulating glycometabolism, affecting cell apoptosis and weakening inflammatory response through targets like IL6, PPARγ, TNF, and mTOR.

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Network Pharmacology Integrated Molecular Docking Reveals the Mechanism of Anisodamine Hydrobromide Injection against Novel Coronavirus Pneumonia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5818107 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Jinsong Su ◽

Zixuan Liu ◽

Chuan Liu ◽

Xuanhao Li ◽

Yi Wang ◽

...

Keyword(s):

Gene Ontology ◽

Molecular Docking ◽

Immune System ◽

Protein Interactions ◽

Viral Infections ◽

Interaction Network ◽

Docking Studies ◽

Network Pharmacology ◽

Immune System Diseases ◽

Topological Parameters

Background. The Coronavirus Disease 2019 (COVID-19) outbreak in Wuhan, China, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anisodamine hydrobromide injection (AHI), the main ingredient of which is anisodamine, is a listed drug for improving microcirculation in China. Anisodamine can improve the condition of patients with COVID-19. Materials and Methods. Protein-protein interactions obtained from the String databases were used to construct the protein interaction network (PIN) of AHI using Cytoscape. The crucial targets of AHI PIN were screened by calculating three topological parameters. Gene ontology and pathway enrichment analyses were performed. The intersection between the AHI component proteins and angiotensin-converting enzyme 2 (ACE2) coexpression proteins was analyzed. We further investigated our predictions of crucial targets by performing molecular docking studies with anisodamine. Results. The PIN of AHI, including 172 nodes and 1454 interactions, was constructed. A total of 54 crucial targets were obtained based on topological feature calculations. The results of Gene Ontology showed that AHI could regulate cell death, cytokine-mediated signaling pathways, and immune system processes. KEGG disease pathways were mainly enriched in viral infections, cancer, and immune system diseases. Between AHI targets and ACE2 coexpression proteins, 26 common proteins were obtained. The results of molecular docking showed that anisodamine bound well to all the crucial targets. Conclusion. The network pharmacological strategy integrated molecular docking to explore the mechanism of action of AHI against COVID-19. It provides protein targets associated with COVID-19 that may be further tested as therapeutic targets of anisodamine.

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