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pmid:33041797

In Silico Prediction of Molecular Targets of Astragaloside IV for Alleviation of COVID-19 Hyperinflammation by Systems Network Pharmacology and Bioinformatic Gene Expression Analysis.

Chenliang Ge · Yan He

Frontiers in pharmacology · 2020 doi:10.3389/fphar.2020.556984

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33041797
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2026-11-01T15:41:12Z
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title
In Silico Prediction of Molecular Targets of Astragaloside IV for Alleviation of COVID-19 Hyperinflammation by Systems Network Pharmacology and Bioinformatic Gene Expression Analysis.
doi
10.3389/fphar.2020.556984
pmid
33041797
authors array · 2 items
[0]
Chenliang Ge
[1]
Yan He
journal
Frontiers in pharmacology
year
2020
abstract
INTRODUCTION: The overproduction of cytokines and chemokines caused by excessive and uncontrolled inflammation contributes to the development of COVID-19. Astragaloside IV is considered as an anti-inflammatory and antioxidant agent. This study aimed at undertaking a network pharmacology approach and bioinformatics analysis to uncover the pharmacological mechanisms of Astragaloside IV on COVID-19. METHODS: Potential targets of Astragaloside IV were screened from public databases. Differentially expressed genes (DEGs) in SARS-CoV-2 were screened using bioinformatics analysis on the Gene Expression Omnibus (GEO) datasets GSE147507. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. The overlapping genes, GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs were confirmed, and the location of overlapping targets in the key pathways was queried using KEGG Mapper. RESULTS: A total of 425 potential targets of Astragaloside IV were screened. Besides, a total of 546 DEGs were identified between SARS-CoV-2 infected samples and control samples, including 380 up-regulated and 166 down-regulated genes. There was a significant overlap in GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs. The shared genes included MMP13, NLRP3, TRIM21, GBP1, ADORA2A, PTAFR, TNF, MLNR, IL1B, NFKBIA, ADRB2, and IL6. CONCLUSIONS: This study is the first to propose Astragaloside IV as a new drug candidate for alleviating hyper-inflammation in COVID-19 patients. Besides, the key targets and pathways may reveal the main pharmacological mechanism of Astragaloside IV in the treatment of COVID-19.
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Transcriptional response to SARS-CoV-2 infection
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33041797", "kind": "science-record", "revision": 8, "content_hash": "sha256:2ca899854c2033b679eb59fb4d3bd886c537293e703e2e6834cda10bc962ffda", "created_at": "2026-11-01T15:41:12Z", "updated_at": "2026-11-01T22:45:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "In Silico Prediction of Molecular Targets of Astragaloside IV for Alleviation of COVID-19 Hyperinflammation by Systems Network Pharmacology and Bioinformatic Gene Expression Analysis.", "doi": "10.3389/fphar.2020.556984", "pmid": "33041797", "authors": ["Chenliang Ge", "Yan He"], "journal": "Frontiers in pharmacology", "year": 2020, "abstract": "INTRODUCTION: The overproduction of cytokines and chemokines caused by excessive and uncontrolled inflammation contributes to the development of COVID-19. Astragaloside IV is considered as an anti-inflammatory and antioxidant agent. This study aimed at undertaking a network pharmacology approach and bioinformatics analysis to uncover the pharmacological mechanisms of Astragaloside IV on COVID-19.\nMETHODS: Potential targets of Astragaloside IV were screened from public databases. Differentially expressed genes (DEGs) in SARS-CoV-2 were screened using bioinformatics analysis on the Gene Expression Omnibus (GEO) datasets GSE147507. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. The overlapping genes, GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs were confirmed, and the location of overlapping targets in the key pathways was queried using KEGG Mapper.\nRESULTS: A total of 425 potential targets of Astragaloside IV were screened. Besides, a total of 546 DEGs were identified between SARS-CoV-2 infected samples and control samples, including 380 up-regulated and 166 down-regulated genes. There was a significant overlap in GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs. The shared genes included MMP13, NLRP3, TRIM21, GBP1, ADORA2A, PTAFR, TNF, MLNR, IL1B, NFKBIA, ADRB2, and IL6.\nCONCLUSIONS: This study is the first to propose Astragaloside IV as a new drug candidate for alleviating hyper-inflammation in COVID-19 patients. Besides, the key targets and pathways may reveal the main pharmacological mechanism of Astragaloside IV in the treatment of COVID-19.", "claims": [{"id": "claim-data-access", "statement": "All datasets presented in this study are included in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33041797", "locator": "sections[15] \"Data Availability Statement\" paragraph 2", "quote": "All datasets presented in this study are included in the article/ Supplementary Material ."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33041797"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE147507"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"fdr_threshold": "with Benjamini-Hochberg false discovery rate adjustment"}, "inputs": ["data:geo:GSE147507"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33041797", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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"Transcriptional response to SARS-CoV-2 infection", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33041797:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5d60837ee241b1f9988407db1cc9eb11c88fae93fb832be158f8e857654c4b09", "bytes": 1049, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#T1", "version": null, "note": "Top 10 overlapping gene ontology (GO) terms between Astragaloside IV targets and SARS-CoV-2 differentially expressed genes (DEGs).", "structure": {"pmcid": "PMC7525161", "section_index": 11, "section_title": "Gene Ontology and KEGG Enrichment Analysis of Astragaloside IV-Related Targets and SARS-CoV-2 DEGs", "row_count": 11, "column_count": 4}, "table": {"label": "Table 1", "caption": "Top 10 overlapping gene ontology (GO) terms between Astragaloside IV targets and SARS-CoV-2 differentially expressed genes (DEGs).", "rows": [["Category term", "Description", "Count", "P value"], ["GO:0002526", "cytokine-mediated signaling pathway", "53", "2.22498E-10"], ["GO:0032755", "regulation of cytokine production", "41", "2.05545E-06"], ["GO:0010874", "second-messenger-mediated signaling", "26", "4.79803E-05"], ["GO:0002438", "positive regulation of cytokine production", "27", "8.37368E-05"], ["GO:0002526", "cytokine secretion", "17", "0.000161558"], ["GO:0032755", "regulation of cytokine secretion", "15", "0.000335339"], ["GO:0002438", "negative regulation of protein secretion", "11", "0.000653223"], ["GO:0002438", "negative regulation of peptide secretion", "11", "0.00095377"], ["GO:0001730", "cellular calcium ion homeostasis", "24", "0.001033831"], ["GO:0002438", "negative regulation of immune system process", "24", "0.001200594"]], "row_count": 11, "column_count": 4, "numeric_cells": 30, "header_rows": 1, "locator": "section[11]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33041797:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:bb8e0f2817dd365e15c893cf4f9a5781acc26ebe50edbc15ed00e776e62e7d5a", "bytes": 676, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T2", "version": null, "note": "The docking scores of Astragaloside IV and Rapamycin with key proteins.", "structure": {"pmcid": "PMC7525161", "section_index": 13, "section_title": "Molecular Docking Analysis", "row_count": 12, "column_count": 4}, "table": {"label": "Table 2", "caption": "The docking scores of Astragaloside IV and Rapamycin with key proteins.", "rows": [["Target", "PDB ID", "Binding energy (kcal/mol)"], ["Astragaloside IV", "Rapamycin"], ["MMP13", "3I7I", "−9.05", "−16.27"], ["IL6", "4CNI", "−9.04", "−20.19"], ["GBP1", "6K1Z", "−8.91", "−13.8"], ["ADRB2", "3D4S", "−8.18", "−14.08"], ["IL1", "5BOW", "−8.16", "−17.84"], ["PTAFR", "5ZKQ", "−7.84", "−16.66"], ["TNF", "2ZJC", "−7.78", "−14.24"], ["ADORA2A", "2YDV", "−7.13", "−12.99"], ["NLRP3", "3QF2", "−6.97", "−12.11"], ["NF-κB", "6GJW", "−6.72", "−12.63"]], "row_count": 12, "column_count": 4, "numeric_cells": 31, "header_rows": 2, "locator": "section[13]/table-wrap[1]#T2"}}], "gaps": ["asset:data:geo:GSE147507 not downloaded", "asset:data:geo:GSE147507 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"fdr_threshold": "with Benjamini-Hochberg false discovery rate adjustment"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "reordered", "quote": "“Original p-values were adjusted using the Benjamini-Hochberg method, and fold-changes (FC) were calculated using the false discovery rate (FDR).”"}}, {"id": "method-2", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE147507"], "resolved_accessions": ["GSE147507"], "statements": ["All datasets presented in this study are included in the article/ Supplementary Material ."], "basis": "The paper names GSE147507 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:33041797", "data:geo:GSE147507", "asset:table:pmid:33041797:1", "asset:table:pmid:33041797:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE147507"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:23:06Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 31268, "completion_tokens": 1220, "cached_tokens": 792}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:33041797", "type": "paper", "label": "pmid:33041797"}, {"id": "source:pmid:33041797", "type": "manuscript", "label": "PMID 33041797 full text"}, {"id": "data:geo:GSE147507", "type": "dataset", "label": "GEO GSE147507"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33041797", "type": "paper", "label": "pmid:33041797"}, {"id": "source:pmid:33041797", "type": "manuscript", "label": "PMID 33041797 full text"}, {"id": "data:geo:GSE147507", "type": "dataset", "label": "GEO GSE147507"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33041797", "type": "extraction", "used": ["source:pmid:33041797"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE147507", "type": "accession_resolution", "used": ["data:geo:GSE147507"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:33041797", "parent_hash": "sha256:8f6bb60276442a9f01a2983e6382e60473457e08e4d5b69a4a64be34238af1bd", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE147507 licence not read", "asset:data:geo:GSE147507 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["“Original p-values were adjusted using the Benjamini-Hochberg method, and fold-changes (FC) were calculated using the false discovery rate (FDR).”"], "order_basis": "analysis_only", "id": "assay:1"}]}