Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34273999", "kind": "science-record", "revision": 7, "content_hash": "sha256:c5efcf945aa498f143bd7b166f4d3a8530717e47879a1c3ca0242af07224ea1c", "created_at": "2026-11-01T15:41:43Z", "updated_at": "2026-11-01T22:04:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology.", "doi": "10.1186/s13018-021-02552-w", "pmid": "34273999", "authors": ["Weijian Chen", "Tianye Lin", "Qi He", "Peng Yang", "Gangyu Zhang", "Fayi Huang", "Zihao Wang", "Hao Peng", "Baolin Li", "Du Liang", "Haibin Wang"], "journal": "Journal of orthopaedic surgery and research", "year": 2021, "abstract": "BACKGROUND: Knee osteoarthritis is a common joint degenerative disease. Xiao Huoluo Pills (XHLP) has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP's specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis.\nMETHODS: Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB > 30%, DL ≥ 0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P value < 0.01, |log2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein.\nRESULTS: XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 upregulated genes and 759 downregulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis.\nCONCLUSIONS: In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis.", "claims": [{"id": "claim-data-access", "statement": "All the data will be available upon motivated request to the corresponding author of the present paper.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34273999", "locator": "sections[24] \"notes\" paragraph 1", "quote": "All the data will be available upon motivated request to the corresponding author of the present paper."}], "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:34273999"], "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:GSE114007"], "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": {}, "inputs": ["data:geo:GSE114007"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34273999", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13018-021-02552-w", "sha256": 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"structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All the data will be available upon motivated request to the corresponding author of the present paper.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3130531", "GSM3130532", "GSM3130533", "GSM3130534", "GSM3130535", "GSM3130536", "GSM3130537", "GSM3130538", "GSM3130539", "GSM3130540", "GSM3130541", "GSM3130542", "GSM3130543", "GSM3130544", "GSM3130545", "GSM3130546", "GSM3130547", "GSM3130548", "GSM3130549", "GSM3130550", "GSM3130551", "GSM3130552", "GSM3130553", "GSM3130554", "GSM3130555", "GSM3130556", "GSM3130557", "GSM3130558", "GSM3130559", "GSM3130560", "GSM3130561", "GSM3130562", "GSM3130563", "GSM3130564", "GSM3130565", "GSM3130566", "GSM3130567", "GSM3130568"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, "platform": "11154;18573", "taxon": "Homo sapiens", "title": "Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis", "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:34273999:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cab68454b93be4fd4cc563b5584d0c7b8e72b3c1580c39feba2a9044bc1ee5cc", "bytes": 395, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#Tab1", "version": null, "note": "Characteristics of study subjects", "structure": {"pmcid": "PMC8285844", "section_index": 5, "section_title": "Obtaining gene expression profile of human osteoarthritis cartilage tissue", "row_count": 4, "column_count": 6}, "table": {"label": "Table 1", "caption": "Characteristics of study subjects", "rows": [["GSE114007", "Number of subjects", "Age (years, mean ± SD)", "Sex", "K-L stage"], ["Male", "Female"], ["Normal", "18", "36.61 ± 13.08", "13", "5", "I(n = 18)"], ["Osteoarthritis", "20", "66.20 ± 7.16", "8", "12", "IV(n = 20)"]], "row_count": 4, "column_count": 6, "numeric_cells": 11, "header_rows": 2, "locator": "section[5]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:34273999:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:28ad6c59dde2f1986e9822288875a08015bf6182e7ea6939bc33681801631d5d", "bytes": 5335, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#Tab2", "version": null, "note": "XHLP effective active component information", "structure": {"pmcid": "PMC8285844", "section_index": 11, "section_title": "Screening of effective active components of XHLP", "row_count": 72, "column_count": 6}, "table": {"label": "Table 2", "caption": "XHLP effective active component information", "rows": [["ID", "Pubchem CId", "Component", "OB (%)", "DL", "Herbs (Latin name)"], ["CHW1", "22212681", "1-[(5R,8R,9S,10S,12R,13S,14S,17S)-12-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone", "33.47", "0.42", "Aconiti Radix"], ["CHW2", "92979", "Delta4,16-Androstadien-3-one", "37.63", "0.31"], ["CAW1", "133323", "Izoteolin", "39.53", "0.51", "Aconitum Kusnezoffii Reichb"], ["CAW2", "441742", "Karakoline", "51.73", "0.73"], ["CAW3", "21598997", "3-Deoxyaconitine", "30.96", "0.24"], ["CAW4", "21599000", "3-Acetylaconitine", "37.05", "0.2"], ["CAW5", "157539", "Crassicauline A", "34.13", "0.21"], ["CAW6", "155569", "yunaconitine", "33.56", "0.2"], ["CAW7", "441749", "Napelline", "34.48", "0.72"], ["DIL1", "–", "Lumbrifebrine", "–", "–", "Pheretima"], ["DIL2", "–", "Lumbritin", "–", "–"], ["DIL3", "–", "Lumbrolysin", "–", "–"], ["TLX1", "22524484", "[(2R)-2-[[[(2R)-2-(benzoylamino)-3-phenylpropanoyl]amino]methyl]-3-phenylpropyl] acetate", "38.88", "0.56", "Arisaematis Rhizoma"], ["TLX2", "5283637", "24-epicampesterol", "37.58", "0.71"], ["TLX3", "12303645", "sitosterol", "36.91", "0.75"], ["TLX4", "5997", "CLR", "37.87", "0.68"], ["TLX5", "5364473", "8,11,14-Docosatrienoic acid, methyl ester", "43.23", "0.3"], ["RUX1", "101257", "tirucallol", "42.12", "0.75", "Olibanun"], ["RUX2", "15181201", "O-acetyl-α-boswellic acid", "42.73", "0.7"], ["RUX3", "637234", "3alpha-Hydroxy-olean-12-en-24-oic-acid", "39.32", "0.75"], ["RUX4", "168928", "Boswellic acid", "39.55", "0.75"], ["RUX5", "44559813", "Phyllocladene", "33.4", "0.27"], ["RUX6", "–", "3-Oxo-tirucallic,acid", "42.86", "0.81"], ["RUX7", "15181201", "Acetyl-alpha-boswellic,acid", "42.73", "0.7"], ["RUX8", "44583885", "Incensole", "45.59", "0.22"], ["MOY1", "13258914", "Quercetin-3-O-β-D-glucuronide", "30.66", "0.74", "Myrrha"], ["MOY2", "5281855", "Ellagic acid", "43.06", "0.43"], ["MOY3", "440832", "Pelargonidin", "37.99", "0.21"], ["MOY4", "5283663", "Poriferasta-7,22E-dien-3beta-ol", "42.98", "0.76"], ["MOY5", "69232409", "Guggulsterol-VI", "54.72", "0.43"], ["MOY6", "128211", "Mansumbinoic acid", "48.1", "0.32"], ["MOY7", "57401582", "Myrrhanol C", "39.96", "0.58"], ["MOY8", "–", "(8R)-3-oxo-8-hydroxy-polypoda -13E,17E,21-triene", "44.83", "0.59"], ["MOY9", "102242792", "Myrrhanones B", "34.39", "0.67"], ["MOY10", "–", "Epimansumbinol", "61.81", "0.4"], ["MOY11", "51407984", "Diayangambin", "63.84", "0.81"], ["MOY12", "667495", "(2R)-5,7-Dihydroxy-2-(4-hydroxyphenyl)chroman-4-one", "42.36", "0.21"], ["MOY13", "–", "(13E,17E,21E)-8-hydroxypolypodo-13,17,21-trien-3-one", "44.34", "0.58"], ["MOY14", "–", "(13E,17E,21E)-polypodo-13,17,21-triene-3,18-diol", "39.96", "0.58"], ["MOY15", "–", "16-Hydroperoxymansumbin-13(17)-en-3β-ol", "41.05", "0.49"], ["MOY16", "–", "Mansumbin-13(17)-en- 3,16-dione", "41.78", "0.45"], ["MOY17", "–", "(16S, 20R)-Dihydroxydammar-24-en-3-one", "37.34", "0.78"], ["MOY18", "5318259", "15α-Hydroxymansumbinone", "37.51", "0.44"], ["MOY19", "636531", "28-Acetoxy-15α-hydroxymansumbinone", "41.85", "0.67"], ["MOY20", "101281214", "Isofouquierone", "40.95", "0.78"], ["MOY21", "11004967", "[(5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,9-tetrahydroisobenzofurano[6,5-f][1,3]benzodioxol-8a-yl] acetate", "44.08", "0.9"], ["MOY22", "–", "Phellamurin_qt", "56.6", "0.39"], ["MOY23", "–", "(3R,20S)-3,20-Dihydroxydammar- 24-ene", "37.49", "0.75"], ["MOY24", "–", "3-Methoxyfuranoguaia-9- en-8-one", "35.15", "0.18"], ["MOY25", "6439929", "Guggulsterone", "42.45", "0.44"], ["MOY26", "441774", "Petunidin", "30.05", "0.31"], ["MOY27", "5280343", "Quercetin", "46.43", "0.28"], ["MOY28", "–", "4,17(20)-(cis)-pregnadiene-3,16-dione", "51.42", "0.48"], ["MOY29", "101297585", "Guggulsterol IV", "33.59", "0.74"], ["MOY30", "10496532", "(7S,8R,9S,10R,13S,14S,17Z)-17-ethylidene-7-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione", "35.75", "0.48"], ["MOY31", "–", "7β,15β- dihydroxypregn-4-ene-3,16-dione", "43.11", "0.51"], ["MOY32", "–", "11α-hydroxypregna-4,17(20)-trans-diene-3,16-dione", "36.62", "0.47"], ["MOY33", "102242791", "myrrhanone A", "40.25", "0.63"], ["MOY34", "–", "3β-acetoxy-16β,20(R)-dihydroxydammar-24-ene", "38.72", "0.81"], ["MOY35", "–", "1α-acetoxy-9,19-cyclolanost-24-en-3β-ol", "44.4", "0.78"], ["MOY36", "12019028", "[(3R,5R,8R,9R,10R,13R,14R,17S)-17-[(2S,5S)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate", "33.07", "0.8"], ["MOY37", "21625900", "cabraleone", "36.21", "0.82"], ["MOY38", "–", "(20S)-3β-acetoxy-12β,16β,25-tetrahydroxydammar-23-ene", "34.89", "0.82"], ["MOY39", "–", "(20S)-3β,12β,16β,25-pentahydroxydammar-23-ene", "37.94", "0.75"], ["MOY40", "–", "(20R)-3β-acetoxy-16β-dihydroxydammar-24-ene", "40.36", "0.82"], ["MOY41", "–", "3β- hydroxydammar-24-ene", "40.27", "0.82"], ["MOY42", "10870920", "[(5S,6R,8R,9Z)-8-methoxy-3,6,10-trimethyl-4-oxo-6,7,8,11-tetrahydro-5H-cyclodeca[b]furan-5-yl] acetate", "34.76", "0.25"], ["MOY43", "–", "2-Methoxyfuranoguaia-9-ene-8-one", "66.18", "0.18"], ["A1", "441737", "hypaconitine", "31.39", "0.26", "Aconiti Radix/Aconitum Kusnezoffii Reichb"], ["B1", "222284", "beta-sitosterol", "36.91", "0.75", "Arisaematis Rhizoma/Myrrha"], ["B2", "5280794", "Stigmasterol", "43.83", "0.76", "Arisaematis Rhizoma/Myrrha"]], "row_count": 72, "column_count": 6, "numeric_cells": 253, "header_rows": 1, "locator": "section[11]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:34273999:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2c97c5aec612a7e2d2325cf55c32a62d4696d87cf39ce39703d793956856eeee", "bytes": 1070, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab3", "version": null, "note": "Degree and BC values of the top 8 effective active components and targets of XHLP", "structure": {"pmcid": "PMC8285844", "section_index": 12, "section_title": "Construction and analysis of XHLP-active component-target network", "row_count": 17, "column_count": 6}, "table": {"label": "Table 3", "caption": "Degree and BC values of the top 8 effective active components and targets of XHLP", "rows": [["Type", "Description", "Degree", "BC", "Link", "Rank"], ["Component", "Quercetin", "136", "0.71368345", "136", "1"], ["Stigmasterol", "52", "0.08655831", "52", "2"], ["Beta-sitosterol", "52", "0.07340369", "52", "3"], ["Izoteolin", "18", "0.07627614", "18", "4"], ["Ellagic acid", "17", "0.03680757", "17", "5"], ["[(5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,9-tetrahydroisobenzofurano[6,5-f][1,3]benzodioxol-8a-yl] acetate", "16", "0.03229396", "16", "6"], ["Pelargonidin", "12", "0.01540433", "12", "7"], ["3-Methoxyfuranoguaia-9- en-8-one", "9", "0.00568861", "9", "8"], ["Gene", "PGR", "25", "0.02750561", "25", "1"], ["NCOA2", "24", "0.07571674", "24", "2"], ["PTGS2", "18", "0.04966347", "18", "3"], ["NR3C2", "18", "0.00563037", "18", "4"], ["RXRA", "12", "0.03377059", "12", "5"], ["PTGS1", "12", "0.03359142", "12", "6"], ["CHRM3", "10", "0.00861658", "10", "7"], ["CHRM1", "10", "0.00440313", "10", "8"]], "row_count": 17, "column_count": 6, "numeric_cells": 66, "header_rows": 1, "locator": "section[12]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:34273999:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ed36968bde53d57ec5e420be9b674b143b96dc5c42ec17840cfd6aadca77df4a", "bytes": 2638, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#Tab4", "version": null, "note": "Annotation of intersection target gene GO/KEGG enrichment analysis", "structure": {"pmcid": "PMC8285844", "section_index": 15, "section_title": "Enrichment analysis of intersection target by GO/KEGG", "row_count": 24, "column_count": 6}, "table": {"label": "Table 4", "caption": "Annotation of intersection target gene GO/KEGG enrichment analysis", "rows": [["Category", "Term", "Description", "Count", "P.adj. value", "Genes"], ["BP", "GO:0070482", "Response to oxygen levels", "11", "0.00000005", "PTGS2,PLAU,VEGFA,CDKN1A,MMP2,PPARG,MYC,ICAM1,COL1A1,SLC2A4,HK2"], ["GO:0009612", "Response to mechanical stimulus", "8", "0.00000150", "PTGS2,JUN,RELA,PPARG,FOS,COL1A1,COL3A1,IRF1"], ["GO:0033273", "Response to vitamin", "6", "0.00000436", "PTGS2,RELA,PPARG,CCND1,COL1A1,SPP1"], ["GO:0048660", "Regulation of smooth muscle cell proliferation", "7", "0.00000436", "PTGS2,JUN,CDKN1A,MMP2,MMP9,PPARG,IGFBP3"], ["GO:0042493", "Response to drug", "9", "0.00000436", 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