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All Studies   Meta Analysis    Recent:   

Therapeutic effect and potential mechanism of curcumin, an active ingredient in Tongnao Decoction, on COVID-19 combined with stroke: a network pharmacology study and GEO database mining

Yunze et al., Research Square, doi:10.21203/rs.3.rs-4329762/v1
May 2024  
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14th treatment shown to reduce risk in February 2021
 
*, now with p = 0.000000015 from 26 studies.
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4,300+ studies for 77 treatments. c19early.org
In Silico study showing that curcumin, the active ingredient in Tongnao Decoction, may be beneficial for COVID-19 combined with stroke through the CCNA2, JAK2, MMP9, PPARG, PTGS2, and STAT3 target pathways, with MMP9 being the most important target. Authors used network pharmacology and GEO database mining to identify 205 overlapping differentially expressed genes between COVID-19 and stroke datasets. Enrichment analysis showed these genes were involved in immune response, inflammation, and signaling pathways. Curcumin was predicted as a candidate treatment and molecular docking showed strong binding of curcumin to the 6 core target proteins.
44 preclinical studies support the efficacy of curcumin for COVID-19:
In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,18,10,21,12,5 (and specifically the receptor binding domainB,8,14,11), MproC,10,21,14,9,22,19,24,7,16,13,34,11,5, RNA-dependent RNA polymeraseD,20,11, ACE2E,12,13,15, nucleocapsidF,6,23, and nsp10G,23 proteins. In Vitro studies demonstrate inhibition of the spikeA,29 (and specifically the receptor binding domainB,37), MproC,34,36,29,17, ACE2E,37, and TMPRSS2H,37 proteins. In Vitro studies demonstrate efficacy in Calu-3I,35, A549J,29, 293TK,1, HEK293-hACE2L,27,17, 293T/hACE2/TMPRSS2M,28, Vero E6N,35,11,21,31,29,27,7,30,33, and SH-SY5YO,26 cells. Curcumin is predicted to inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain and the human ACE2 receptor for the delta and omicron variants8, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells33, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress1.
Yunze et al., 29 May 2024, preprint, 10 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Therapeutic effect and potential mechanism of curcumin, an active ingredient in Tongnao Decoction, on COVID-19 combined with stroke: a network pharmacology study and GEO database mining
Li Yunze, Yao Yangjing, Mao Rui, Wu Jiacheng, Liu Yan, Feng Qinghua, Hu Manyan, Chen Weiwei, Wu Minghua, Li Jianjun
doi:10.21203/rs.3.rs-4329762/v1
Background The onset of severe acute respiratory syndrome coronavirus type 2 at the end of 2019 led to a global pandemic of acute respiratory diseases, commonly known as COVID-19, caused by this highly infectious and pathogenic coronavirus. As members of the Fifth-batch National TCM Medical Team sent by the A liated Hospital of Nanjing University of Chinese Medicine to assist Wuhan Jiangxia Mobile Cabin Hospital, it was observed that patients with COVID-19 had an elevated incidence of stroke and are prone to progression. The possible mechanisms included neuroinvasion by the virus, an imbalance between ACE1 and ACE2, hypercoagulability, and a pre-thrombotic state. However, effective treatment options are not yet available. Developed by the Department of Neurology, A liated Hospital of Nanjing University of Chinese Medicine, Tongnao Decoction (TND) is a prescribed medication. The chemical components within the TND extract were previously examined using Waters ACQUITY UPLC ultra-performance liquid chromatography. Notably, identi ed chemical constituents, including curcumin, exhibited protective effects on brain cells. In the current investigation, bioinformatics techniques were employed to mine the GEO database, aiming to assess the functional role and potential action mechanism of curcumin as a therapeutic agent for COVID-19 combined with stroke.Tongnao Decoction Methods The datasets of COVID-19 and stroke were retrieved from the GEO database to identify the differentially intersecting genes (DIGs) between the two diseases. These DIGs were then exposed to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses employing
Declarations 6 Data availability The data used to support the results of this study are available from the rst and corresponding authors. of interest: The authors declare that they have no known competing nancial interests or personal relationships that could have appeared to in uence the work reported in this paper. The owchart of the analysis process.
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As members of the Fifth-batch National TCM ' 'Medical Team sent by the Affiliated Hospital of Nanjing University of Chinese Medicine to ' 'assist Wuhan Jiangxia Mobile Cabin Hospital, it was observed that patients with COVID-19 had ' 'an elevated incidence of stroke and are prone to progression. The possible mechanisms ' 'included neuroinvasion by the virus, an imbalance between ACE1 and ACE2, hypercoagulability, ' 'and a pre-thrombotic state. However, effective treatment options are not yet available. ' 'Developed by the Department of Neurology, Affiliated Hospital of Nanjing University of ' 'Chinese Medicine, Tongnao Decoction (TND) is a prescribed medication. The chemical components ' 'within the TND extract were previously examined using Waters ACQUITY UPLC ultra-performance ' 'liquid chromatography. Notably, identified chemical constituents, including curcumin, ' 'exhibited protective effects on brain cells. In the current investigation, bioinformatics ' 'techniques were employed to mine the GEO database, aiming to assess the functional role and ' 'potential action mechanism of curcumin as a therapeutic agent for COVID-19 combined with ' 'stroke.Tongnao Decoction\n' 'Methods\n' ' The datasets of COVID-19 and stroke were retrieved from the GEO database to identify the ' 'differentially intersecting genes (DIGs) between the two diseases. These DIGs were then ' 'exposed to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway ' 'enrichment analyses employing the clusterProfiler to extract TF genes in the Trrust database ' '(TF in TRRUST). Core TF genes were found to be target genes in DEGs-related TF in Stroke and ' 'DEGs-related TF in COVID. The overlapping set of these target genes yielded intersected ' 'target genes, which were then imported into the DGIdb website for drug prediction. ' 'Subsequently, the selected core drugs were subjected to drug validation on the cMAP website. ' 'Target prediction was performed on four online platforms: SEA, SwissTargetPrediction, ' 'TargetNet, and TCMSP. Subsequently, the obtained results were imported into the String ' 'database to create an interaction network comprising core target genes and enriched pathways. ' 'Additionally, molecular docking was performed using AutoDock software. Finally, molecular ' 'docking scoring was applied to the core targets.\n' 'Results\n' ' The intersection of DEGs from stroke dataset GSE16561 with DEGs from COVID dataset GSE211979 ' 'yielded 205 intersected genes. These intersected genes, including E2F3, BCL6, ETS2, CEBPD, ' 'STAT1, MXD1, NFIL3, HDAC4, MMP9, CD163, FCGR1A, IFIT3, LY96, PLSCR1, TNFSF10:E2F3, BCL6, ' 'ETS2, CEBPD, STAT1, MXD1, NFIL3, HDAC4, MMP9, CD163, FCGR1A, IFIT3, LY96, PLSCR1, and ' 'TNFSF10, were subjected to GO and KEGG pathway enrichment analyses utilizing the ' 'clusterProfiler. Subsequently, the core drug curcumin was selected from the 17 intersected ' 'drugs. Curcumin inhibits NF-κb and MAPKs and possesses various pharmacological effects ' 'encompassing anti-proliferative, anti-oxidant, anti-inflammatory, and anti-angiogenic ' 'effects. The six core targets CCNA2, JAK2, MMP9, PPARG, PTGS2, and STAT3 had molecular ' 'docking scores of -2.86, -2.98, -5.01, -2.42, -3.83, and −\u20092.28, respectively.\n' 'Conclusion\n' ' Curcumin, the active ingredient in TND, can effectively intervene in COVID-19 combined with ' 'stroke through CCNA2, JAK2, MMP9, PPARG, PTGS2, and STAT3 target pathways, of which the most ' 'important target is MMP9.</p>', 'DOI': '10.21203/rs.3.rs-4329762/v1', 'type': 'posted-content', 'created': {'date-parts': [[2024, 5, 29]], 'date-time': '2024-05-29T01:55:37Z', 'timestamp': 1716947737000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Therapeutic effect and potential mechanism of curcumin, an active ingredient in Tongnao ' 'Decoction, on COVID-19 combined with stroke: a network pharmacology study and GEO database ' 'mining', 'prefix': '10.21203', 'author': [ { 'given': 'Li', 'family': 'Yunze', 'sequence': 'first', 'affiliation': [ { 'name': 'Affiliated Hospital of Nanjing University of Chinese Medicine, ' 'Nanjing University of Chinese Medicine'}]}, { 'given': 'Yao', 'family': 'Yangjing', 'sequence': 'additional', 'affiliation': [ { 'name': 'Affiliated Hospital of Nanjing University of Chinese Medicine, ' 'Nanjing University of Chinese Medicine'}]}, { 'given': 'Mao', 'family': 'Rui', 'sequence': 'additional', 'affiliation': [{'name': 'Lianyungang Food and Drug Inspection Center'}]}, { 'given': 'Wu', 'family': 'Jiacheng', 'sequence': 'additional', 'affiliation': [{'name': 'Nanjing Medical University Friendship Plastic Surgery Hospital'}]}, { 'given': 'Liu', 'family': 'Yan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Affiliated Hospital of Nanjing University of Chinese Medicine, ' 'Nanjing University of Chinese Medicine'}]}, { 'given': 'Feng', 'family': 'Qinghua', 'sequence': 'additional', 'affiliation': [ { 'name': 'Affiliated Hospital of Nanjing University of Chinese Medicine, ' 'Nanjing University of Chinese Medicine'}]}, { 'given': 'Hu', 'family': 'Manyan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Affiliated Hospital of Nanjing University of Chinese Medicine, ' 'Nanjing University of Chinese Medicine'}]}, { 'given': 'Chen', 'family': 'Weiwei', 'sequence': 'additional', 'affiliation': [ { 'name': 'Affiliated Hospital of Nanjing University of Chinese Medicine, ' 'Nanjing University of Chinese Medicine'}]}, { 'given': 'Wu', 'family': 'Minghua', 'sequence': 'additional', 'affiliation': [ { 'name': 'Affiliated Hospital of Nanjing University of Chinese Medicine, ' 'Nanjing University of Chinese Medicine'}]}, { 'given': 'Li', 'family': 'Jianjun', 'sequence': 'additional', 'affiliation': [{'name': 'Lianyungang Hospital of Traditional Chinese Medicine'}]}], 'member': '8761', 'container-title': [], 'original-title': [], 'link': [ { 'URL': 'https://www.researchsquare.com/article/rs-4329762/v1', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.researchsquare.com/article/rs-4329762/v1.html', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 5, 29]], 'date-time': '2024-05-29T01:55:37Z', 'timestamp': 1716947737000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.researchsquare.com/article/rs-4329762/v1'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 5, 29]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.21203/rs.3.rs-4329762/v1', 'relation': {}, 'subject': [], 'published': {'date-parts': [[2024, 5, 29]]}, 'subtype': 'preprint'}
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