All Studies Meta Analysis

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

Post
Facebook

Source PDF All Studies Meta AnalysisMeta

Curcumin for COVID-19

15th treatment shown to reduce risk in February 2021, now with p = 0.0000000096 from 27 studies.

Lower risk for mortality, ventilation, hospitalization, progression, recovery, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,100+ studies for 109 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.

48 preclinical studies support the efficacy of curcumin for COVID-19:

24 In Silico studies1-24

23 In Vitro studies1,5,7,11,17,21,25-41

1 In Vivo animal study5

In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,5,10,12,18,21 (and specifically the receptor binding domainB,8,11,14), M^proC,5,7,9-11,13,14,16,19,21,22,24,38, RNA-dependent RNA polymeraseD,11,20, ACE2E,12,13,15, nucleocapsidF,6,23, nsp10G,23, and helicaseH,27 proteins. In Vitro studies demonstrate inhibition of the spikeA,32 (and specifically the receptor binding domainB,41), M^proC,17,32,38,40, ACE2E,41, and TMPRSS2I,41 proteins, and inhibition of spike-ACE2 interactionJ,25. In Vitro studies demonstrate efficacy in Calu-3K,39, A549L,32, 293TM,1, HEK293-hACE2N,17,30, 293T/hACE2/TMPRSS2O,31, Vero E6P,7,11,21,30,32,34,35,37,39, and SH-SY5YQ,29 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 cells37, alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress1, may limit COVID-19 induced cardiac damage by inhibiting the NF-κB signaling pathway which mediates the profibrotic effects of the SARS-CoV-2 spike protein on cardiac fibroblasts42, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity33.

Important missing comments or errors? Let us know.

1. Zhang et al., Computational Discovery of Mitochondrial Dysfunction Biomarkers in Severe SARS-CoV-2 Infection: Facilitating Pytomedicine Screening, Phytomedicine, doi:10.1016/j.phymed.2024.155784.sciencedirect.com, doi.org.

2. Öztürkkan et al., In Silico investigation of the effects of curcuminoids on the spike protein of the omicron variant of SARS-CoV-2, Baku State University Journal of Chemistry and Material Sciences, 1:2, bsuj.bsu.edu.az/uploads/pdf/ec4204d62f7802de54e6092bf7860029.pdf.edu.az.

3. Yunze et al., 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, Research Square, doi:10.21203/rs.3.rs-4329762/v1.researchsquare.com, doi.org.

4. Agamah et al., Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases, ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1.scienceopen.com, doi.org.

5. Boseila et al., Throat spray formulated with virucidal Pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS CoV-2, European Journal of Pharmaceutics and Biopharmaceutics, doi:10.1016/j.ejpb.2024.114279.sciencedirect.com, doi.org.

6. Hidayah et al., Bioinformatics study of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds in Curcuma longa as an antiviral agent via nucleocapsid on SARS-CoV-2 inhibition, International Conference on Organic and Applied Chemistry, doi:10.1063/5.0197724.aip.org, doi.org.

7. Singh et al., Unlocking the potential of phytochemicals in inhibiting SARS-CoV-2 M Pro protein - An in-silico and cell-based approach, Research Square, doi:10.21203/rs.3.rs-3888947/v1.researchsquare.com, doi.org.

8. Kant et al., Structure-based drug discovery to identify SARS-CoV2 spike protein–ACE2 interaction inhibitors, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2023.2300060.tandfonline.com, doi.org.

9. Naderi Beni et al., In silico studies of anti-oxidative and hot temperament-based phytochemicals as natural inhibitors of SARS-CoV-2 Mpro, PLOS ONE, doi:10.1371/journal.pone.0295014.plos.org, doi.org.

10. Moschovou et al., Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein, International Journal of Molecular Sciences, doi:10.3390/ijms242115894.mdpi.com, doi.org.

11. Eleraky et al., Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2, International Journal of Nanomedicine, doi:10.2147/IJN.S423251.dovepress.com, doi.org.

12. Singh (B) et al., Computational studies to analyze effect of curcumin inhibition on coronavirus D614G mutated spike protein, The Seybold Report, doi:10.17605/OSF.IO/TKEXJ.ac.in, doi.org.

13. Thapa et al., In-silico Approach for Predicting the Inhibitory Effect of Home Remedies on Severe Acute Respiratory Syndrome Coronavirus-2, Makara Journal of Science, doi:10.7454/mss.v27i3.1609.ac.id, doi.org.

14. Srivastava et al., Paradigm of Well-Orchestrated Pharmacokinetic Properties of Curcuminoids Relative to Conventional Drugs for the Inactivation of SARS-CoV-2 Receptors: An In Silico Approach, Stresses, doi:10.3390/stresses3030043.mdpi.com, doi.org.

15. Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.biomedcentral.com, doi.org.

16. Winih Kinasih et al., Analisis in silico interaksi senyawa kurkuminoid terhadap enzim main protease 6LU7 dari SARS-CoV-2, Duta Pharma Journal, doi:10.47701/djp.v3i1.2904.ac.id, doi.org.

17. Wu et al., Potential Mechanism of Curcumin and Resveratrol against SARS-CoV-2, Research Square, doi:10.21203/rs.3.rs-2780614/v1.researchsquare.com, doi.org.

18. Nag et al., Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2022.105552.sciencedirect.com, doi.org.

19. Rampogu et al., Molecular Docking and Molecular Dynamics Simulations Discover Curcumin Analogue as a Plausible Dual Inhibitor for SARS-CoV-2, International Journal of Molecular Sciences, doi:10.3390/ijms23031771.mdpi.com, doi.org.

20. Singh (C) et al., Potential of turmeric-derived compounds against RNA-dependent RNA polymerase of SARS-CoV-2: An in-silico approach, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2021.104965.sciencedirect.com, doi.org.

21. Kandeil et al., Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2, Pathogens, doi:10.3390/pathogens10060758.mdpi.com, doi.org.

22. Rajagopal et al., Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach, Future Journal of Pharmaceutical Sciences, doi:10.1186/s43094-020-00126-x.springeropen.com, doi.org.

23. Suravajhala et al., Comparative Docking Studies on Curcumin with COVID-19 Proteins, Preprints, doi:10.20944/preprints202005.0439.v3.preprints.org, doi.org.

24. Sekiou et al., In-Silico Identification of Potent Inhibitors of COVID-19 Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) from Natural Products: Quercetin, Hispidulin, and Cirsimaritin Exhibited Better Potential Inhibition than Hydroxy-Chloroquine Against COVID-19 Main Protease Active Site and ACE2, ChemRxiv, doi:10.26434/chemrxiv.12181404.v1.chemrxiv.org, doi.org.

25. Emam et al., Establishment of in-house assay for screening of anti-SARS-CoV-2 protein inhibitors, AMB Express, doi:10.1186/s13568-024-01739-8.springeropen.com, doi.org.

26. Van Tin et al., Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling, Cells, doi:10.3390/cells13161331.mdpi.com, doi.org.

27. Li et al., Thermal shift assay (TSA)-based drug screening strategy for rapid discovery of inhibitors against the Nsp13 helicase of SARS-CoV-2, Animals and Zoonoses, doi:10.1016/j.azn.2024.06.001.sciencedirect.com, doi.org.

28. Kamble et al., Nanoparticulate curcumin spray imparts prophylactic and therapeutic properties against SARS-CoV-2, Emergent Materials, doi:10.1007/s42247-024-00754-6.springer.com, doi.org.

29. Nicoliche et al., Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2, Scientific Reports, doi:10.1038/s41598-024-61662-7.nature.com, doi.org.

30. Nittayananta et al., A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity, Virology Journal, doi:10.1186/s12985-023-02282-x.biomedcentral.com, doi.org.

31. Septisetyani et al., Curcumin and turmeric extract inhibited SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion, bioRxiv, doi:10.1101/2023.09.28.560070.biorxiv.org, doi.org.

32. Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.sagepub.com, doi.org.

33. Fam et al., Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites, Scientific Reports, doi:10.1038/s41598-023-31764-9.nature.com, doi.org.

34. Teshima et al., Antiviral activity of curcumin and its analogs selected by an artificial intelligence-supported activity prediction system in SARS-CoV-2-infected VeroE6 cells, Natural Product Research, doi:10.1080/14786419.2023.2194647.tandfonline.com, doi.org.

35. Leka et al., In vitro antiviral activity against SARS-CoV-2 of common herbal medicinal extracts and their bioactive compounds, Phytotherapy Research, doi:10.1002/ptr.7463.wiley.com, doi.org.

36. Goc et al., Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants, European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022.akjournals.com, doi.org.

37. Marín-Palma et al., Curcumin Inhibits In Vitro SARS-CoV-2 Infection In Vero E6 Cells through Multiple Antiviral Mechanisms, Molecules, doi:10.3390/molecules26226900.mdpi.com, doi.org.

38. Bahun et al., Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols, Food Chemistry, doi:10.1016/j.foodchem.2021.131594.sciencedirect.com, doi.org.

39. Bormann et al., Turmeric Root and Its Bioactive Ingredient Curcumin Effectively Neutralize SARS-CoV-2 In Vitro, Viruses, doi:10.3390/v13101914.mdpi.com, doi.org.

40. Guijarro-Real et al., Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity, Foods, doi:10.3390/foods10071503.mdpi.com, doi.org.

41. Goc (B) et al., Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions, PLOS ONE, doi:10.1371/journal.pone.0253489.plos.org, doi.org.

42. Van Tin (B) et al., Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling, Cells, doi:10.3390/cells13161331.mdpi.com, doi.org.

a. The trimeric spike (S) protein is a glycoprotein that mediates viral entry by binding to the host ACE2 receptor, is critical for SARS-CoV-2's ability to infect host cells, and is a target of neutralizing antibodies. Inhibition of the spike protein prevents viral attachment, halting infection at the earliest stage.

b. The receptor binding domain is a specific region of the spike protein that binds ACE2 and is a major target of neutralizing antibodies. Focusing on the precise binding site allows highly specific disruption of viral attachment with reduced potential for off-target effects.

c. The main protease or M^pro, also known as 3CL^pro or nsp5, is a cysteine protease that cleaves viral polyproteins into functional units needed for replication. Inhibiting M^pro disrupts the SARS-CoV-2 lifecycle within the host cell, preventing the creation of new copies.

d. RNA-dependent RNA polymerase (RdRp), also called nsp12, is the core enzyme of the viral replicase-transcriptase complex that copies the positive-sense viral RNA genome into negative-sense templates for progeny RNA synthesis. Inhibiting RdRp blocks viral genome replication and transcription.

e. The angiotensin converting enzyme 2 (ACE2) protein is a host cell transmembrane protein that serves as the cellular receptor for the SARS-CoV-2 spike protein. ACE2 is expressed on many cell types, including epithelial cells in the lungs, and allows the virus to enter and infect host cells. Inhibition may affect ACE2's physiological function in blood pressure control.

f. The nucleocapsid (N) protein binds and encapsulates the viral genome by coating the viral RNA. N enables formation and release of infectious virions and plays additional roles in viral replication and pathogenesis. N is also an immunodominant antigen used in diagnostic assays.

g. Non-structural protein 10 (nsp10) serves as an RNA chaperone and stabilizes conformations of nsp12 and nsp14 in the replicase-transcriptase complex, which synthesizes new viral RNAs. Nsp10 disruption may destabilize replicase-transcriptase complex activity.

h. The helicase, or nsp13, protein unwinds the double-stranded viral RNA, a crucial step in replication and transcription. Inhibition may prevent viral genome replication and the creation of new virus components.

i. Transmembrane protease serine 2 (TMPRSS2) is a host cell protease that primes the spike protein, facilitating cellular entry. TMPRSS2 activity helps enable cleavage of the spike protein required for membrane fusion and virus entry. Inhibition may especially protect respiratory epithelial cells, buy may have physiological effects.

j. The interaction between the SARS-CoV-2 spike protein and the human ACE2 receptor is a primary method of viral entry, inhibiting this interaction can prevent the virus from attaching to and entering host cells, halting infection at an early stage.

k. Calu-3 is a human lung adenocarcinoma cell line with moderate ACE2 and TMPRSS2 expression and SARS-CoV-2 susceptibility. It provides a model of the human respiratory epithelium, but many not be ideal for modeling early stages of infection due to the moderate expression levels of ACE2 and TMPRSS2.

l. A549 is a human lung carcinoma cell line with low ACE2 expression and SARS-CoV-2 susceptibility. Viral entry/replication can be studied but the cells may not replicate all aspects of lung infection.

m. 293T is a human embryonic kidney cell line that can be engineered for high ACE2 expression and SARS-CoV-2 susceptibility. 293T cells are easily transfected and support high protein expression.

n. HEK293-hACE2 is a human embryonic kidney cell line with high ACE2 expression and SARS-CoV-2 susceptibility. Cells have been transfected with a plasmid to express the human ACE2 (hACE2) protein.

o. 293T/hACE2/TMPRSS2 is a human embryonic kidney cell line engineered for high ACE2 and TMPRSS2 expression, which mimics key aspects of human infection. 293T/hACE2/TMPRSS2 cells are very susceptible to SARS-CoV-2 infection.

p. Vero E6 is an African green monkey kidney cell line with low/no ACE2 expression and high SARS-CoV-2 susceptibility. The cell line is easy to maintain and supports robust viral replication, however the monkey origin may not accurately represent human responses.

q. SH-SY5Y is a human neuroblastoma cell line that exhibits neuronal phenotypes. It is commonly used as an in vitro model for studying neurotoxicity, neurodegenerative diseases, and neuronal differentiation.

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 Paper Curcumin All

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.

References

Ao, Yan, Zhou, Immune cells after ischemic stroke onset: roles, migration, and target intervention[J], Journal of Molecular Neuroscience

Broman, Rantasärkkä, Feuth, IL-6 and other biomarkers as predictors of severity in COVID-19[J], Annals of medicine

Cai, Xu, Bai, Curcumin mitigates cerebral vasospasm and early brain injury following subarachnoid hemorrhage via inhibiting cerebral in ammation, J]. Brain and behavior

Chaturvedi, Kaczmarek, Mmp-9 inhibition: a therapeutic strategy in ischemic stroke[J], Molecular neurobiology

Chuyu, Jianming, Xiangyu, Therapeutic effect and mechanism of curcumin on cerebral ischemia-reperfusion injury in rats, J]. Shandong Medicine

Ghoneim, Khalifa, Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain[J], Pharmacological research

Grzela, Litwiniuk, Zagorska, Airway remodeling in chronic obstructive pulmonary disease and asthma: the role of matrix metalloproteinase-9[J], Archivum immunologiae et therapiae experimentalis

Guo, Wu, Effects of irisin on the dysfunction of blood-brain barrier in rats after focal cerebral ischemia/reperfusion, J]. Brain and behavior

Hadid, Kafri, Al-Katib, Coagulation and anticoagulation in COVID-19, J]. Blood Reviews

Hongtao, Youling, Fang, Curcumin alleviates ischemia reperfusion-induced late kidney brosis through the APPL1/Akt signaling pathway[J], Journal of Cellular Physiology

Hu, Guo, Zhou, Characteristics of SARS-CoV-2 and COVID-19[J], Nature Reviews Microbiology

Huang, Chen, Zhang, Neuroprotective effect of curcumin against cerebral ischemiareperfusion via mediating autophagy and in ammation[J], Journal of Molecular Neuroscience

Huang, Han, Sheng, Shen, Identi cation of immune-related biomarkers associated with tumorigenesis and prognosis in cutaneous melanoma patients, Cancer Cell Int

Jianli, Mechanism and clinical signi cance of activating PI3K/Akt signaling pathway by Tongnao Decoction on angiogenesis after ischemic stroke[D, Nanjing university of Chinese medicine, doi:10.27253/d.cnki.gnjzu.2022.000714

Ke, Clinical E cacy evaluation of carotid artery stenting combined with Tongnao Decoction in the treatment of phlegm-stasis blocked collateral-collateral cognitive dysfunction, Nanjing university of Chinese medicine, doi:10.27253/d.cnki.gnjzu.2022.000065

Kremer, Lersy, Anheim, Neurologic and neuroimaging ndings in patients with COVID-19: A retrospective multicenter study, J]. Neurology

Lin, Clinical study of Tongnao Decoction in the treatment of carotid atherosclerotic vulnerable plaque based on plaque neovascularization, Nanjing university of Chinese medicine, doi:10.27253/d.cnki.gnjzu.2022.000502

Liu, Ying, The inhibitory effect of curcumin on virus-induced cytokine storm and its potential use in the associated severe pneumonia[J], Frontiers in cell and developmental biology

Lu, Liu, Dong, Su, Zhou et al., Discovering common pathogenetic processes between COVID-19 and sepsis by bioinformatics and system biology approach, Front Immunol

Majidi, Fi, Ladner T R, Emergent large vessel occlusion stroke during New York City's COVID-19 outbreak: clinical characteristics and paraclinical ndings, J]. Stroke

Mao, Wang, Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China[J, JAMA neurology

Maurya, Kumar, Prasad, Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor, Virusdisease

Meilun, Aihui, Expression and function of receptors for advanced glycosylation end products and intracellular signaling molecules in lung adenocarcinoma cells, Journal of Anhui Medical University, doi:10.19405/j.cnkiissn1000-1492.2019.02.016

Merkler, Parikh, Mir, Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with in uenza[J], JAMA neurology

Min, Lei, Mingli, Curcumin inhibits hypoxia-induced in ammation in microglia through the miR-182-TLR4 pathway[J], Advances in Anatomical Sciences

Napoli, Benincasa, Criscuolo, Immune reactivity during COVID-19: Implications for treatment, J]. Immunology letters

Pang, Yu, Chen, Yuan, Sheng et al., Integrating Single-cell RNA-seq to construct a Neutrophil prognostic model for predicting immune responses in non-small cell lung cancer, J Transl Med

Planas, Solé, Justicia, Expression and activation of matrix metalloproteinase-2 and-9 in rat brain after transient focal cerebral ischemia, J]. Neurobiology of disease

Rui, Yafei, Xiaoli, Effect and mechanism of curcumin on chronic obstructive pulmonary disease in rats[J], Chinese Journal of New Medicine and Clinical Medicine

Saidi, Kasabova, Vanderlynden, Curcumin inhibits the TGF-β1-dependent differentiation of lung broblasts via PPARγ-driven upregulation of cathepsins B and L[J], Scienti c reports

Shen, Zhou, Liu, Yang, Huang et al., Prediction of Mechanosensitive Genes in Vascular Endothelial Cells Under High Wall Shear Stress, Front Genet

Shi Chanmei, Huang Kunlun, Jingqi, Research progress of curcumin on pulmonary diseases[J], Journal of Medical Research

Ting, Dong, Fang, Multisite inhibitors for enteric coronavirus: antiviral cationic carbon dots based on curcumin[J], ACS Applied Nano Materials

Wang, Wu, The up-regulation of miR-21 by gastrodin to promote the angiogenesis ability of human umbilical vein endothelial cells by activating the signaling pathway of PI3K/Akt[J], Bioengineered

Wang, Xia, Shen, Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroin ammation by suppressing JAK1/STAT1 pathway[J], Biochemistry and Cell Biology

Wang, Zhang, Xu, Pro-angiogenic activity of Tongnao decoction on HUVECs in vitro and zebra sh in vivo[J], Journal of ethnopharmacology

Yang, Estrada, Thompson, Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat[J], Journal of Cerebral Blood Flow & Metabolism

Yavarpour-Bali, Ghasemi-Kasman, Pirzadeh, Curcumin-loaded nanoparticles: A novel therapeutic strategy in treatment of central nervous system disorders[J], International journal of nanomedicine

Yiwen, Evaluation of clinical e cacy and prognosis of Tongnao Decoction in the treatment of acute ischemic stroke based on peripheral blood NLR and PLR, Nanjing university of Chinese medicine, doi:10.27253/d.cnki.gnjzu.2022.000376

Yu, Guo, Liu, Immune Characteristics Analysis and Transcriptional Regulation Prediction Based on Gene Signatures of Chronic Obstructive Pulmonary Disease

Yu, Zhang, Zhuo, Hong, Ye et al., Identi cation of Diagnostic Signatures and Immune Cell In ltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies, Front Immunol

Yunze, Suofang, Yangjing, New coronavirus pneumonia recovery 86 cases of patients with clinical characteristics analysis, Journal of Liaoning University of Traditional Chinese Medicine, doi:10.13194/j.issn.1673-842x.2020.09.029

Yunze, Yangjing, Anqi, Clinical effect observation on 374 cases of novel coronavirus pneumonia complicated with anxiety and depression treated by TCM psychological sandbox, J]. Medical Food Therapy and Health

Yunze, Yangjing, Kun, Clinical e cacy of Anshen Granules in treating 110 cases of novel coronavirus pneumonia complicated with insomnia[J], Journal of Liaoning Traditional Chinese Medicine, doi:10.13192/j.issn.1000-1719.2020.10.026

Yunze, Yangjing, Nan, TCM psychological Sandplay can be applied in the treatment of psychological problems of medical personnel ghting against novel coronavirus infection pneumonia, Journal of Zhejiang University of Chinese Medicine, doi:10.16466/j.issn1005-5509.2020

Zhang, Chen, Qu, Curcumin alleviates oxygen-glucose-deprivation/reperfusion-induced oxidative damage by regulating miR-1287-5p/LONP2 axis in SH-SY5Y cells, J]. Analytical Cellular Pathology, doi:10.1155/2021/5548706

Zhang, Zhang, Li, Wang, Yan et al., Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea, Front Immunol

Zou, Li, Huang, Chen, Liu et al., Identi cation of molecular correlations of RBM8A with autophagy in Alzheimer's disease, Aging

{ 'institution': [{'name': 'Research Square'}], 'indexed': {'date-parts': [[2024, 5, 29]], 'date-time': '2024-05-29T02:10:36Z', 'timestamp': 1716948636665}, 'posted': {'date-parts': [[2024, 5, 29]]}, 'group-title': 'In Review', 'reference-count': 0, 'publisher': 'Research Square Platform LLC', 'license': [ { 'start': { 'date-parts': [[2024, 5, 29]], 'date-time': '2024-05-29T00:00:00Z', 'timestamp': 1716940800000}, 'content-version': 'unspecified', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2024, 4, 26]]}, 'abstract': '<title>Abstract</title>\n' ' <p>Background\n' ' 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 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'}

Download Image

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0