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image of Screening of Phytocompounds Against the NF-kB Pathway Genes and Lung Elevated Proteins Associated with Acute Respiratory Distress Syndrome

Abstract

Introduction

Acute Respiratory Distress Syndrome (ARDS) is the pathophysiologic state of the inflammatory response to lung injury characterized by alveolar epithelial cell damage and increased cytokine production and accumulation in the lungs.

Objectives

The current study was performed to identify the molecular mechanisms of ARDS related to the proteins elevated in the lung (PEL) and NF-κB pathway regulatory genes (GRNF). In addition, the phytocompounds were screened to inhibit the representative target genes and proteins associated with ARDS.

Materials and Methods

We implemented STRING v11.5 and Network Analyst 3.0 to construct the protein-protein interactions (PPI) network. CytoScape v3.8.2 and DisGeNet v7.3.0 were utilized to visualize and identify genes involved in respiratory diseases. The Cytohubba module was utilized to identify the hub genes from the constructed PPI network. Autodock Vina and Discovery Studio Visualizer v19.1.0.1828 were utilized for the molecular docking analysis.

Results

The PPI network was constructed with the GRNF genes. Fifty-four genes are identified as biomarkers involved in respiratory diseases (BMRD). About 191 PEL were identified from the human protein atlas database and constructed the PPI network. The interactions between the PPI network of BMRD and PEL were analyzed. The top 100 hub genes and the signaling genes were identified. Based on the identified signaling genes through the PPI network of BMRD and PEL, the metabolic pathway was elucidated, which causes ARDS NF-κB activation. The ARDS targets (ACVRL1, IKKβ, ITGAL, ITGB2, TGFβR1, and TGFβR2) were selected for the molecular docking study. One hundred and thirty-five chemical compounds from , , Linn., , and Linn. were retrieved and used for docking against selected ARDS targets. Among them, genkdaphine from inhibited ACVRL1 (binding affinity of -9.2 kcal/mol, and RMSD of 2.607Å), ITGAL (binding affinity of -9.1 kcal/mol, and RMSD of 1.69Å), ITGB2 (binding affinity of -7.9 kcal/mol, and RMSD of 2.184Å), TGFβRI (binding affinity of -8.5 kcal/mol, and RMSD of 1.807Å), and TGFβRII (binding affinity of -8.2 kcal/mol, and RMSD of 1.647Å). Edulisin III from inhibited the IKKβ (binding affinity of -7.4 kcal/mol, and RMSD of 2.223Å).

Conclusion

Genkdaphine and edulisin III may be the therapeutics for treating ARDS. However, further studies are needed to warrant the benefits of genkdaphine and edulisin III in treating ARDS. The study's findings may aid in developing new therapeutic approaches to improve the health status of ARDS-affected patients.

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2025-03-24
2025-09-02

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References

  1. Geddes D. The history of respiratory disease management. Medicine (Abingdon) 2020 48 4 239 243 10.1016/j.mpmed.2020.01.007 32288588
    [Google Scholar]
  2. Hikichi M. Mizumura K. Maruoka S. Gon Y. Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke. J. Thorac. Dis. 2019 11 S17 S2129 S2140 10.21037/jtd.2019.10.43
    [Google Scholar]
  3. Soriano J.B. Kendrick P.J. Paulson K.R. Gupta V. Abrams E.M. Adedoyin R.A. Adhikari T.B. Advani S.M. Agrawal A. Ahmadian E. Alahdab F. Aljunid S.M. Altirkawi K.A. Alvis-Guzman N. Anber N.H. Andrei C.L. Anjomshoa M. Ansari F. Antó J.M. Arabloo J. Athari S.M. Athari S.S. Awoke N. Badawi A. Banoub J.A.M. Bennett D.A. Bensenor I.M. Berfield K.S.S. Bernstein R.S. Bhattacharyya K. Bijani A. Brauer M. Bukhman G. Butt Z.A. Cámera L.A. Car J. Carrero J.J. Carvalho F. Castañeda-Orjuela C.A. Choi J-Y.J. Christopher D.J. Cohen A.J. Dandona L. Dandona R. Dang A.K. Daryani A. de Courten B. Demeke F.M. Demoz G.T. De Neve J-W. Desai R. Dharmaratne S.D. Diaz D. Douiri A. Driscoll T.R. Duken E.E. Eftekhari A. Elkout H. Endries A.Y. Fadhil I. Faro A. Farzadfar F. Fernandes E. Filip I. Fischer F. Foroutan M. Garcia-Gordillo M.A. Gebre A.K. Gebremedhin K.B. Gebremeskel G.G. Gezae K.E. Ghoshal A.G. Gill P.S. Gillum R.F. Goudarzi H. Guo Y. Gupta R. Hailu G.B. Hasanzadeh A. Hassen H.Y. Hay S.I. Hoang C.L. Hole M.K. Horita N. Hosgood H.D. Hostiuc M. Househ M. Ilesanmi O.S. Ilic M.D. Irvani S.S.N. Islam S.M.S. Jakovljevic M. Jamal A.A. Jha R.P. Jonas J.B. Kabir Z. Kasaeian A. Kasahun G.G. Kassa G.M. Kefale A.T. Kengne A.P. Khader Y.S. Khafaie M.A. Khan E.A. Khan J. Khubchandani J. Kim Y-E. Kim Y.J. Kisa S. Kisa A. Knibbs L.D. Komaki H. Koul P.A. Koyanagi A. Kumar G.A. Lan Q. Lasrado S. Lauriola P. La Vecchia C. Le T.T. Leigh J. Levi M. Li S. Lopez A.D. Lotufo P.A. Madotto F. Mahotra N.B. Majdan M. Majeed A. Malekzadeh R. Mamun A.A. Manafi N. Manafi F. Mantovani L.G. Meharie B.G. Meles H.G. Meles G.G. Menezes R.G. Mestrovic T. Miller T.R. Mini G.K. Mirrakhimov E.M. Moazen B. Mohammad K.A. Mohammed S. Mohebi F. Mokdad A.H. Molokhia M. Monasta L. Moradi M. Moradi G. Morawska L. Mousavi S.M. Musa K.I. Mustafa G. Naderi M. Naghavi M. Naik G. Nair S. Nangia V. Nansseu J.R. Nazari J. Ndwandwe D.E. Negoi R.I. Nguyen T.H. Nguyen C.T. Nguyen H.L.T. Nixon M.R. Ofori-Asenso R. Ogbo F.A. Olagunju A.T. Olagunju T.O. Oren E. Ortiz J.R. Owolabi M.O. P A M. Pakhale S. Pana A. Panda-Jonas S. Park E-K. Pham H.Q. Postma M.J. Pourjafar H. Poustchi H. Radfar A. Rafiei A. Rahim F. Rahman M.H.U. Rahman M.A. Rawaf S. Rawaf D.L. Rawal L. Reiner R.C. Jr Reitsma M.B. Roever L. Ronfani L. Roro E.M. Roshandel G. Rudd K.E. Sabde Y.D. Sabour S. Saddik B. Safari S. Saleem K. Samy A.M. Santric-Milicevic M.M. Sao Jose B.P. Sartorius B. Satpathy M. Savic M. Sawhney M. Sepanlou S.G. Shaikh M.A. Sheikh A. Shigematsu M. Shirkoohi R. Si S. Siabani S. Singh V. Singh J.A. Soljak M. Somayaji R. Soofi M. Soyiri I.N. Tefera Y.M. Temsah M-H. Tesfay B.E. Thakur J.S. Toma A.T. Tortajada-Girbés M. Tran K.B. Tran B.X. Tudor Car L. Ullah I. Vacante M. Valdez P.R. van Boven J.F.M. Vasankari T.J. Veisani Y. Violante F.S. Wagner G.R. Westerman R. Wolfe C.D.A. Wondafrash D.Z. Wondmieneh A.B. Yonemoto N. Yoon S-J. Zaidi Z. Zamani M. Zar H.J. Zhang Y. Vos T. GBD Chronic Respiratory Disease Collaborators Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir. Med. 2020 8 6 585 596 10.1016/S2213‑2600(20)30105‑3 32526187
    [Google Scholar]
  4. Gould G.S. Hurst J.R. Trofor A. Alison J.A. Fox G. Kulkarni M.M. Wheelock C.E. Clarke M. Kumar R. Recognising the importance of chronic lung disease: A consensus statement from the Global Alliance for Chronic Diseases (Lung Diseases group). Respir. Res. 2023 24 1 15 10.1186/s12931‑022‑02297‑y 36639661
    [Google Scholar]
  5. Mermiri M. Mavrovounis G. Kanellopoulos N. Papageorgiou K. Spanos M. Kalantzis G. Saharidis G. Gourgoulianis K. Pantazopoulos I. Effect of PM2.5 levels on ed visits for respiratory causes in a Greek Semi-Urban area. J. Pers. Med. 2022 12 11 1849 10.3390/jpm12111849 36579575
    [Google Scholar]
  6. Rhee J. Dominici F. Zanobetti A. Schwartz J. Wang Y. Di Q. Balmes J. Christiani D.C. Impact of long-term exposures to ambient PM2.5 and ozone on ARDS risk for older adults in the United States. Chest 2019 156 1 71 79 10.1016/j.chest.2019.03.017 30926395
    [Google Scholar]
  7. Gutman L. Pauly V. Orleans V. Piga D. Channac Y. Armengaud A. Boyer L. Papazian L. Long-term exposure to ambient air pollution is associated with an increased incidence and mortality of acute respiratory distress syndrome in a large French region. Environ. Res. 2022 212 Pt D 113383 10.1016/j.envres.2022.113383 35569534
    [Google Scholar]
  8. Choi J.Y. Song J.W. Rhee C.K. Chronic obstructive pulmonary disease combined with interstitial lung disease. Tuberc. Respir. Dis. (Seoul) 2022 85 2 122 136 10.4046/trd.2021.0141 35385639
    [Google Scholar]
  9. Myall K.J. Mukherjee B. Castanheira A.M. Lam J.L. Benedetti G. Mak S.M. Preston R. Thillai M. Dewar A. Molyneaux P.L. West A.G. Persistent post-COVID-19 interstitial lung disease. An observational study of corticosteroid treatment. Ann. Am. Thorac. Soc. 2021 18 5 799 806 10.1513/AnnalsATS.202008‑1002OC 33433263
    [Google Scholar]
  10. Patel V.J. Biswas Roy S. Mehta H.J. Joo M. Sadikot R.T. Alternative and natural therapies for acute lung injury and acute respiratory distress syndrome. BioMed Res. Int. 2018 2018 1 9 10.1155/2018/2476824 29862257
    [Google Scholar]
  11. Rebetz J. Semple J.W. Kapur R. The pathogenic involvement of neutrophils in acute respiratory distress syndrome and transfusion-related acute lung injury. Transfus. Med. Hemother. 2018 45 5 290 298 10.1159/000492950 30498407
    [Google Scholar]
  12. Han S. Mallampalli R.K. The role of surfactant in lung disease and host defense against pulmonary infections. Ann. Am. Thorac. Soc. 2015 a 12 5 765 774 10.1513/AnnalsATS.201411‑507FR 25742123
    [Google Scholar]
  13. Han S. Mallampalli R.K. The acute respiratory distress syndrome: From mechanism to translation. J. Immunol. 2015 b 194 3 855 860 10.4049/jimmunol.1402513 25596299
    [Google Scholar]
  14. Liu T. Zhang L. Joo D. Sun S.C. NF-κB signaling in inflammation. Signal Transduct. Target. Ther. 2017 2 1 17023 10.1038/sigtrans.2017.23 29158945
    [Google Scholar]
  15. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb. Perspect. Biol. 2009 1 6 a001651 10.1101/cshperspect.a001651 20457564
    [Google Scholar]
  16. Liu C.W. Lee T.L. Chen Y.C. Liang C.J. Wang S.H. Lue J.H. Tsai J.S. Lee S.W. Chen S.H. Yang Y.F. Chuang T.Y. Chen Y.L. PM2.5-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway. Part. Fibre Toxicol. 2018 15 1 4 10.1186/s12989‑018‑0240‑x 29329563
    [Google Scholar]
  17. Bajwa E.K. Cremer P.C. Gong M.N. Zhai R. Su L. Thompson B.T. Christiani D.C. An NFKB1 promoter insertion/deletion polymorphism influences risk and outcome in acute respiratory distress syndrome among Caucasians. PLoS One 2011 6 5 e19469 10.1371/journal.pone.0019469 21573030
    [Google Scholar]
  18. Hojyo S. Uchida M. Tanaka K. Hasebe R. Tanaka Y. Murakami M. Hirano T. How COVID-19 induces cytokine storm with high mortality. Inflamm. Regen. 2020 40 1 37 10.1186/s41232‑020‑00146‑3 33014208
    [Google Scholar]
  19. Shih R.H. Wang C.Y. Yang C.M. NF-kappaB signaling pathways in neurological inflammation: A mini review. Front. Mol. Neurosci. 2015 8 77 10.3389/fnmol.2015.00077 26733801
    [Google Scholar]
  20. Hariharan A. Hakeem A.R. Radhakrishnan S. Reddy M.S. Rela M. The role and therapeutic potential of NF-kappa-B pathway in severe covid-19 patients. Inflammopharmacology 2021 29 1 91 100 10.1007/s10787‑020‑00773‑9 33159646
    [Google Scholar]
  21. Gong C.X. Liu F. Iqbal K. Multifactorial hypothesis and multi-targets for alzheimer’s disease. J. Alzheimers Dis. 2018 64 s1 S107 S117 10.3233/JAD‑179921 29562523
    [Google Scholar]
  22. Habtemariam S. Natural products in alzheimer’s disease therapy: Would old therapeutic approaches fix the broken promise of modern medicines? Molecules 2019 24 8 1519 10.3390/molecules24081519 30999702
    [Google Scholar]
  23. Noori T. Dehpour A.R. Sureda A. Sobarzo-Sanchez E. Shirooie S. Role of natural products for the treatment of Alzheimer’s disease. Eur. J. Pharmacol. 2021 898 173974 10.1016/j.ejphar.2021.173974 33652057
    [Google Scholar]
  24. Karunaweera N. Raju R. Gyengesi E. Münch G. Plant polyphenols as inhibitors of NF-κB induced cytokine production: A potential anti-inflammatory treatment for Alzheimer’s disease? Front. Mol. Neurosci. 2015 8 24 10.3389/fnmol.2015.00024 26136655
    [Google Scholar]
  25. Jha N.K. Jha S.K. Kar R. Nand P. Swati K. Goswami V.K. Nuclear factor‐kappa β as a therapeutic target for Alzheimer’s disease. J. Neurochem. 2019 150 2 113 137 10.1111/jnc.14687 30802950
    [Google Scholar]
  26. Sun B. Karin M. NF-κB signaling, liver disease and hepatoprotective agents. Oncogene 2008 27 48 6228 6244 10.1038/onc.2008.300 18931690
    [Google Scholar]
  27. Santana F.P.R. Pinheiro N.M. Mernak M.I.B. Righetti R.F. Martins M.A. Lago J.H.G. Lopes F.D.T.Q.S. Tibério I.F.L.C. Prado C.M. Evidences of herbal medicine-derived natural products effects in inflammatory lung diseases. Mediators Inflamm. 2016 2016 1 14 10.1155/2016/2348968 27445433
    [Google Scholar]
  28. Murphy E.J. Masterson C. Rezoagli E. O’Toole D. Major I. Stack G.D. Lynch M. Laffey J.G. Rowan N.J. β-Glucan extracts from the same edible shiitake mushroom Lentinus edodes produce differential in-vitro immunomodulatory and pulmonary cytoprotective effects: Implications for coronavirus disease (COVID-19) immunotherapies. Sci. Total Environ. 2020 732 139330 10.1016/j.scitotenv.2020.139330 32413619
    [Google Scholar]
  29. Peddapalli A. Gehani M. Kalle A.M. Peddapalli S.R. Peter A.E. Sharad S. Demystifying excess immune response in covid-19 to reposition an orphan drug for down-regulation of nf-κb: A systematic review. Viruses 2021 13 3 378 10.3390/v13030378 33673529
    [Google Scholar]
  30. Johnson E.R. Matthay M.A. Acute lung injury: Epidemiology, pathogenesis, and treatment. J. Aerosol Med. Pulm. Drug Deliv. 2010 23 4 243 252 10.1089/jamp.2009.0775 20073554
    [Google Scholar]
  31. Fang C.L. Wen C.J. Aljuffali I.A. Sung C.T. Huang C.L. Fang J.Y. Passive targeting of phosphatiosomes increases rolipram delivery to the lungs for treatment of acute lung injury: An animal study. J. Control. Release 2015 213 69 78 10.1016/j.jconrel.2015.06.038 26164036
    [Google Scholar]
  32. Yu H.P. Liu F.C. Lin C.Y. Umoro A. Trousil J. Hwang T.L. Fang J.Y. Suppression of neutrophilic inflammation can be modulated by the droplet size of anti-inflammatory nanoemulsions. Nanomedicine (Lond.) 2020 15 8 773 791 10.2217/nnm‑2019‑0407 32193978
    [Google Scholar]
  33. Okeke E.B. Louttit C. Fry C. Najafabadi A.H. Han K. Nemzek J. Moon J.J. Inhibition of neutrophil elastase prevents neutrophil extracellular trap formation and rescues mice from endotoxic shock. Biomaterials 2020 238 119836 10.1016/j.biomaterials.2020.119836 32045782
    [Google Scholar]
  34. Araz O. Current pharmacological approach to ARDS: The place of Bosentan. Eurasian J. Med. 2020 52 1 81 85 10.5152/eurasianjmed.2020.19218 32158321
    [Google Scholar]
  35. Thompson B.T. Chambers R.C. Liu K.D. Acute respiratory distress syndrome. N. Engl. J. Med. 2017 377 6 562 572 10.1056/NEJMra1608077 28792873
    [Google Scholar]
  36. Sauer A. Peukert K. Putensen C. Bode C. Antibiotics as immunomodulators: A potential pharmacologic approach for ARDS treatment. Eur. Respir. Rev. 2021 30 162 210093 10.1183/16000617.0093‑2021 34615700
    [Google Scholar]
  37. Vichare R. Janjic J.M. Macrophage-targeted nanomedicines for ARDS/ALI: Promise and potential. Inflammation 2022 45 6 2124 2141 10.1007/s10753‑022‑01692‑3 35641717
    [Google Scholar]
  38. Sadikot R. Christman J. Blackwell T. Molecular targets for modulating lung inflammation and injury. Curr. Drug Targets 2004 5 6 581 588 10.2174/1389450043345281 15270205
    [Google Scholar]
  39. Mavers M. Ruderman E.M. Perlman H. Intracellular signal pathways: Potential for therapies. Curr. Rheumatol. Rep. 2009 11 5 378 385 10.1007/s11926‑009‑0054‑9 19772834
    [Google Scholar]
  40. Yuan Z. Syed M. Panchal D. Joo M. Bedi C. Lim S. Onyuksel H. Rubinstein I. Colonna M. Sadikot R.T. TREM-1-accentuated lung injury viamiR-155 is inhibited by LP17 nanomedicine. Am. J. Physiol. Lung Cell. Mol. Physiol. 2016 310 5 L426 L438 10.1152/ajplung.00195.2015 26684249
    [Google Scholar]
  41. El-Saber Batiha G. Magdy Beshbishy A. G Wasef L. Elewa Y.H.A. A Al-Sagan A. Abd El-Hack M.E. Taha A.E. M Abd-Elhakim Y. Prasad Devkota H. Chemical constituents and pharmacological activities of garlic (Allium sativum L.): A review. Nutrients 2020 12 3 872 10.3390/nu12030872 32213941
    [Google Scholar]
  42. Zhou H.X. Li R.F. Wang Y.F. Shen L.H. Cai L.H. Weng Y.C. Zhang H.R. Chen X.X. Wu X. Chen R.F. Jiang H.M. Wang C. Yang M. Lu J. Luo X.D. Jiang Z. Yang Z.F. Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response. Phytomedicine 2020 77 153272 10.1016/j.phymed.2020.153272 32702592
    [Google Scholar]
  43. Bhagavathula A.S. Mahmoud Al-Khatib A.J. Elnour A.A. Al Kalbani N.M. Shehab A. Ammi Visnaga in treatment of urolithiasis and hypertriglyceridemia. Pharmacognosy Res. 2014 7 4 397 400 26692756
    [Google Scholar]
  44. Kim S.Y. Shin D.U. Eom J.E. Jung S.Y. Song H.J. Lim K. Kim G.D. Yun S.I. Kim M.Y. Shin H.S. Lee S.Y. Artemisia gmelinii attenuates lung inflammation by suppressing the NF-κB/MAPK pathway. Antioxidants 2022 11 3 568 10.3390/antiox11030568 35326218
    [Google Scholar]
  45. Wu Z. Deng X. Hu Q. Xiao X. Jiang J. Ma X. Wu M. Houttuynia cordata Thunb: An ethnopharmacological review. Front. Pharmacol. 2021 12 714694 10.3389/fphar.2021.714694 34539401
    [Google Scholar]
  46. Dharsono H.D.A. Putri S.A. Kurnia D. Dudi D. Satari M.H. Ocimum species: A review on chemical constituents and antibacterial activity. Molecules 2022 27 19 6350 10.3390/molecules27196350 36234883
    [Google Scholar]
  47. Thul P.J. Lindskog C. The human protein atlas: A spatial map of the human proteome. Protein Sci. 2018 27 1 233 244 10.1002/pro.3307 28940711
    [Google Scholar]
  48. Szklarczyk D. Gable A.L. Nastou K.C. Lyon D. Kirsch R. Pyysalo S. Doncheva N.T. Legeay M. Fang T. Bork P. Jensen L.J. von Mering C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021 49 D1 D605 D612 10.1093/nar/gkaa1074 33237311
    [Google Scholar]
  49. Shannon P. Markiel A. Ozier O. Baliga N.S. Wang J.T. Ramage D. Amin N. Schwikowski B. Ideker T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003 13 11 2498 2504 10.1101/gr.1239303 14597658
    [Google Scholar]
  50. Piñero J. Ramírez-Anguita J.M. Saüch-Pitarch J. Ronzano F. Centeno E. Sanz F. Furlong L.I. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res. 2020 48 D1 D845 D855 31680165
    [Google Scholar]
  51. Chin C.H. Chen S.H. Wu H.H. Ho C.W. Ko M.T. Lin C.Y. cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol. 2014 8 S4 Suppl. 4 S11 10.1186/1752‑0509‑8‑S4‑S11 25521941
    [Google Scholar]
  52. Zhou G. Soufan O. Ewald J. Hancock R.E.W. Basu N. Xia J. NetworkAnalyst 3.0: A visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res. 2019 47 W1 W234 W241 10.1093/nar/gkz240 30931480
    [Google Scholar]
  53. Kanehisa M. Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000 28 1 27 30 10.1093/nar/28.1.27 10592173
    [Google Scholar]
  54. Jassal B. Matthews L. Viteri G. Gong C. Lorente P. Fabregat A. Sidiropoulos K. Cook J. Gillespie M. Haw R. Loney F. May B. Milacic M. Rothfels K. Sevilla C. Shamovsky V. Shorser S. Varusai T. Weiser J. Wu G. Stein L. Hermjakob H. D’Eustachio P. The reactome pathway knowledgebase. Nucleic Acids Res. 2020 48 D1 D498 D503 31691815
    [Google Scholar]
  55. Kerr G. Sheldon H. Chaikuad A. Alfano I. von Delft F. Bullock A.N. Harris A.L. A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis. Angiogenesis 2015 18 2 209 217 10.1007/s10456‑014‑9457‑y 25557927
    [Google Scholar]
  56. Polley S. Huang D.B. Hauenstein A.V. Fusco A.J. Zhong X. Vu D. Schröfelbauer B. Kim Y. Hoffmann A. Verma I.M. Ghosh G. Huxford T. A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation. PLoS Biol. 2013 11 6 e1001581 10.1371/journal.pbio.1001581 23776406
    [Google Scholar]
  57. Crump M.P. Ceska T.A. Spyracopoulos L. Henry A. Archibald S.C. Alexander R. Taylor R.J. Findlow S.C. O’Connell J. Robinson M.K. Shock A. Structure of an allosteric inhibitor of LFA-1 bound to the I-domain studied by crystallography, NMR, and calorimetry. Biochemistry 2004 43 9 2394 2404 10.1021/bi035422a 14992576
    [Google Scholar]
  58. Sen M. Springer T.A. Leukocyte integrin α L β 2 headpiece structures: The αI domain, the pocket for the internal ligand, and concerted movements of its loops. Proc. Natl. Acad. Sci. USA 2016 113 11 2940 2945 10.1073/pnas.1601379113 26936951
    [Google Scholar]
  59. Guckian K. Carter M.B. Lin E.Y.S. Choi M. Sun L. Boriack-Sjodin P.A. Chuaqui C. Lane B. Cheung K. Ling L. Lee W.C. Pyrazolone based TGFβR1 kinase inhibitors. Bioorg. Med. Chem. Lett. 2010 20 1 326 329 10.1016/j.bmcl.2009.10.108 19914068
    [Google Scholar]
  60. Wangkanont K. Forest K.T. Kiessling L.L. Extracellular domain of type II Transforming growth factor beta receptor in complex with 2-(2-Hydroxyethyl)NDSB-201. 2015
  61. Sivaraman R. Natarajan S. Pattiyappan S. GC-MS analysis of Artemisia vulgaris Linn. Int. J. Biosci. 2015 2 105 109
    [Google Scholar]
  62. Joshi R.K. GC—MS analysis of the essential oil of Ocimum gratissimum L. growing desolately in South India. Acta Chromatogr. 2017 29 1 111 119 10.1556/1326.2017.29.1.10
    [Google Scholar]
  63. Ashraf S.A. Ahmad Khan M. Awadelkareem A.M. Tajuddin S. Ahmad M.F. Hussain T. GC-MS analysis of commercially available Allium sativum and trigonella foenum-graecum essential oils and their antimicrobial activities. J. Pure Appl. Microbiol. 2019 13 4 2545 2552 10.22207/JPAM.13.4.69
    [Google Scholar]
  64. Goyal M.H. Laxmikant V.S. Comparative GC-MS analysis of Alstonia scholaris (L.) R. Br leaf extract using methanol and hexane solvent. IJRAR 2020 7 729 740
    [Google Scholar]
  65. Alaatabi M.R. Almousawi U.M.N. Mosa M.N. Hamarashid S.H. Phytochemical screening by using TLC and GC-MS methods for qualitative determination of compounds in Ammi visnaga L. extract. Plant Arch. 2020 20 4326 4330
    [Google Scholar]
  66. Kharnaior S. Thomas S.C. Preliminary screening of Houttuynia cordata for biological potential and chemical components using TLC and GC–MS analysis. J. Plant Biochem. Biotechnol. 2020 29 3 539 552 10.1007/s13562‑020‑00572‑x
    [Google Scholar]
  67. Kim S. Chen J. Cheng T. Gindulyte A. He J. He S. Li Q. Shoemaker B.A. Thiessen P.A. Yu B. Zaslavsky L. Zhang J. Bolton E.E. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res. 2021 49 D1 D1388 D1395 10.1093/nar/gkaa971 33151290
    [Google Scholar]
  68. Dallakyan S. Olson A.J. Small-molecule library screening by docking with PyRx. Methods Mol. Biol. 2015 1263 243 250 10.1007/978‑1‑4939‑2269‑7_19 25618350
    [Google Scholar]
  69. Kumari R. Dalal V. Identification of potential inhibitors for LLM of Staphylococcus aureus : Structure-based pharmacophore modeling, molecular dynamics, and binding free energy studies. J. Biomol. Struct. Dyn. 2022 40 20 9833 9847 10.1080/07391102.2021.1936179 34096457
    [Google Scholar]
  70. Siddiqui Q. Ali M.S.M. Leow A.T.C. Oslan S.N. Mohd Shariff F. In silico identification and characterization of potential druggable targets among hypothetical proteins of Leptospira interrogans serovar Copenhageni: A comprehensive bioinformatics approach. J. Biomol. Struct. Dyn. 2023 41 20 10347 10367 10.1080/07391102.2022.2154845 36510668
    [Google Scholar]
  71. PyMOL The PyMOL molecular graphics system, version 2.0 Schrödinger. https://www.pymol.org/
  72. Xiong G. Wu Z. Yi J. Fu L. Yang Z. Hsieh C. Yin M. Zeng X. Wu C. Lu A. Chen X. Hou T. Cao D. ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res. 2021 49 W1 W5 W14 10.1093/nar/gkab255 33893803
    [Google Scholar]
  73. Banerjee P. Eckert A.O. Schrey A.K. Preissner R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018 46 W1 W257 W263 10.1093/nar/gky318 29718510
    [Google Scholar]
  74. Qiu Y.Q. KEGG Pathway Database. https://www.kegg.jp/entry/pathway+map04010 2022
  75. Cosentino-Gomes D. Rocco-Machado N. Meyer-Fernandes J.R. Cell signaling through protein kinase C oxidation and activation. Int. J. Mol. Sci. 2012 13 9 10697 10721 10.3390/ijms130910697 23109817
    [Google Scholar]
  76. Kang Q. Yang C. Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biol. 2020 37 101799 10.1016/j.redox.2020.101799 33248932
    [Google Scholar]
  77. Hinz M. Scheidereit C. The IκB kinase complex in NF ‐κB regulation and beyond. EMBO Rep. 2014 15 1 46 61 10.1002/embr.201337983 24375677
    [Google Scholar]
  78. Adli M. Merkhofer E. Cogswell P. Baldwin A.S. IKKalpha and IKKbeta each function to regulate NF-kappaB activation in the TNF-induced/canonical pathway. PLoS One 2010 5 2 e9428 10.1371/journal.pone.0009428 20195534
    [Google Scholar]
  79. Mercurio F. Zhu H. Murray B.W. Shevchenko A. Bennett B.L. Li J. Young D.B. Barbosa M. Mann M. Manning A. Rao A. IKK-1 and IKK-2: Cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 1997 278 5339 860 866 10.1126/science.278.5339.860 9346484
    [Google Scholar]
  80. Zandi E. Rothwarf D.M. Delhase M. Hayakawa M. Karin M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 1997 91 2 243 252 10.1016/S0092‑8674(00)80406‑7 9346241
    [Google Scholar]
  81. Chu W.M. Ostertag D. Li Z.W. Chang L. Chen Y. Hu Y. Williams B. Perrault J. Karin M. JNK2 and IKKbeta are required for activating the innate response to viral infection. Immunity 1999 11 6 721 731 10.1016/S1074‑7613(00)80146‑6 10626894
    [Google Scholar]
  82. Tsoutsou P.G. Gourgoulianis K.I. Petinaki E. Mpaka M. Efremidou S. Maniatis A. Molyvdas P.A. ICAM-1, ICAM-2 and ICAM-3 in the sera of patients with idiopathic pulmonary fibrosis. Inflammation 2004 28 6 359 364 10.1007/s10753‑004‑6647‑6 16245079
    [Google Scholar]
  83. Wang J. Huang J. Wang L. Chen C. Yang D. Jin M. Bai C. Song Y. Urban particulate matter triggers lung inflammation via the ROS-MAPK-NF-κB signaling pathway. J. Thorac. Dis. 2017 9 11 4398 4412 10.21037/jtd.2017.09.135 29268509
    [Google Scholar]
  84. Figenschau S.L. Knutsen E. Urbarova I. Fenton C. Elston B. Perander M. Mortensen E.S. Fenton K.A. ICAM1 expression is induced by proinflammatory cytokines and associated with TLS formation in aggressive breast cancer subtypes. Sci. Rep. 2018 8 1 11720 10.1038/s41598‑018‑29604‑2 30082828
    [Google Scholar]
  85. Pua L.J.W. Mai C.W. Chung F.F.L. Khoo A.S.B. Leong C.O. Lim W.M. Hii L.W. Functional roles of JNK and p38 MAPK signaling in nasopharyngeal carcinoma. Int. J. Mol. Sci. 2022 23 3 1108 10.3390/ijms23031108 35163030
    [Google Scholar]
  86. Deng T. Karin M. c-Fos transcriptional activity stimulated by H-Ras-activated protein kinase distinct from JNK and ERK. Nature 1994 371 6493 171 175 10.1038/371171a0 8072547
    [Google Scholar]
  87. Park E.R. Eblen S.T. Catling A.D. MEK1 activation by PAK: A novel mechanism. Cell. Signal. 2007 19 7 1488 1496 10.1016/j.cellsig.2007.01.018 17314031
    [Google Scholar]
  88. Guo D. Zhang J.J. Huang X.Y. A new Rac/PAK/GC/cGMP signaling pathway. Mol. Cell. Biochem. 2010 334 1-2 99 103 10.1007/s11010‑009‑0327‑7 19937092
    [Google Scholar]
  89. Guégan J.P. Frémin C. Baffet G. The MAPK MEK1/2-ERK1/2 pathway and its implication in hepatocyte cell cycle control. Int. J. Hepatol. 2012 2012 1 13 10.1155/2012/328372 23133759
    [Google Scholar]
  90. Lucas R.M. Luo L. Stow J.L. ERK1/2 in immune signalling. Biochem. Soc. Trans. 2022 50 5 1341 1352 10.1042/BST20220271 36281999
    [Google Scholar]
  91. Zhou L. Xue C. Chen Z. Jiang W. He S. Zhang X. c-Fos is a mechanosensor that regulates inflammatory responses and lung barrier dysfunction during ventilator-induced acute lung injury. BMC Pulm. Med. 2022 22 1 9 10.1186/s12890‑021‑01801‑2 34986829
    [Google Scholar]
  92. Neuzillet C. Tijeras-Raballand A. Cohen R. Cros J. Faivre S. Raymond E. de Gramont A. Targeting the TGFβ pathway for cancer therapy. Pharmacol. Ther. 2015 147 22 31 10.1016/j.pharmthera.2014.11.001 25444759
    [Google Scholar]
  93. Shi N. Wang Z. Zhu H. Liu W. Zhao M. Jiang X. Zhao J. Ren C. Zhang Y. Luo L. Research progress on drugs targeting the TGF-β signaling pathway in fibrotic diseases. Immunol. Res. 2022 70 3 276 288 10.1007/s12026‑022‑09267‑y 35147920
    [Google Scholar]
  94. Adachi M. Gazel A. Pintucci G. Shuck A. Shifteh S. Ginsburg D. Rao L.S. Kaneko T. Freedberg I.M. Tamaki K. Blumenberg M. Specificity in stress response: Epidermal keratinocytes exhibit specialized UV-responsive signal transduction pathways. DNA Cell Biol. 2003 22 10 665 677 10.1089/104454903770238148 14611688
    [Google Scholar]
  95. Hu Y. Wang Q. Yu J. Zhou Q. Deng Y. Liu J. Zhang L. Xu Y. Xiong W. Wang Y. Tartrate-resistant acid phosphatase 5 promotes pulmonary fibrosis by modulating β-catenin signaling. Nat. Commun. 2022 13 1 114 10.1038/s41467‑021‑27684‑9 35013220
    [Google Scholar]
  96. Valenta T. Hausmann G. Basler K. The many faces and functions of β-catenin. EMBO J. 2012 31 12 2714 2736 10.1038/emboj.2012.150 22617422
    [Google Scholar]
  97. Kuo Y.L. Jou I.M. Jeng S.F. Chu C.H. Huang J.S. Hsu T.I. Chang L.R. Huang P.W. Chen J.A. Chou T.M. Hypoxia-induced epithelial-mesenchymal transition and fibrosis for the development of breast capsular contracture. Sci. Rep. 2019 9 1 10269 10.1038/s41598‑019‑46439‑7 31311941
    [Google Scholar]
  98. Freudlsperger C. Bian Y. Contag Wise S. Burnett J. Coupar J. Yang X. Chen Z. Van Waes C. TGF-β and NF-κB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers. Oncogene 2013 32 12 1549 1559 10.1038/onc.2012.171 22641218
    [Google Scholar]
  99. Chang H.Y. Nishitoh H. Yang X. Ichijo H. Baltimore D. Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science 1998 281 5384 1860 1863 10.1126/science.281.5384.1860 9743501
    [Google Scholar]
  100. Perlman R. Schiemann W.P. Brooks M.W. Lodish H.F. Weinberg R.A. TGF-β-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation. Nat. Cell Biol. 2001 3 8 708 714 10.1038/35087019 11483955
    [Google Scholar]
  101. Tobiume K. Matsuzawa A. Takahashi T. Nishitoh H. Morita K. Takeda K. Minowa O. Miyazono K. Noda T. Ichijo H. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep. 2001 2 3 222 228 10.1093/embo‑reports/kve046 11266364
    [Google Scholar]
  102. Valenca S.S. Dong B.E. Gordon E.M. Sun R.C. Waters C.M. ASK1 regulates bleomycin-induced pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 2022 66 5 484 496 10.1165/rcmb.2021‑0465OC 35148253
    [Google Scholar]
  103. König H.G. Kögel D. Rami A. Prehn J.H.M. TGF-β1 activates two distinct type I receptors in neurons. J. Cell Biol. 2005 168 7 1077 1086 10.1083/jcb.200407027 15781474
    [Google Scholar]
  104. Wicks I.P. Roberts A.W. Targeting GM-CSF in inflammatory diseases. Nat. Rev. Rheumatol. 2016 12 1 37 48 10.1038/nrrheum.2015.161 26633290
    [Google Scholar]
  105. Wu H. Huang M. Cao P. Wang T. Shu Y. Liu P. MiR-135a targets JAK2 and inhibits gastric cancer cell proliferation. Cancer Biol. Ther. 2012 13 5 281 288 10.4161/cbt.18943 22310976
    [Google Scholar]
  106. Kiu H. Nicholson S.E. Biology and significance of the JAK/STAT signalling pathways. Growth Factors 2012 30 2 88 106 10.3109/08977194.2012.660936 22339650
    [Google Scholar]
  107. Schwartze J.T. Becker S. Sakkas E. Wujak Ł.A. Niess G. Usemann J. Reichenberger F. Herold S. Vadász I. Mayer K. Seeger W. Morty R.E. Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-β signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts. J. Biol. Chem. 2014 289 6 3262 3275 10.1074/jbc.M113.541052 24347165
    [Google Scholar]
  108. Zhang X. Zhang C. Li Q. Piao C. Zhang H. Gu H. Clinical characteristics and prognosis analysis of idiopathic and hereditary pulmonary hypertension patients with ACVRL1 gene mutations. Pulm. Circ. 2021 11 4 1 8 10.1177/20458940211044577 34966542
    [Google Scholar]
  109. Huang Q. Le Y. Li S. Bian Y. Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS). Respir. Res. 2024 25 1 30 10.1186/s12931‑024‑02678‑5 38218783
    [Google Scholar]
  110. Li Q. Xiao C. Gu J. Chen X. Yuan J. Li S. Li W. Gao D. Li L. liu Y. Shen F. 6-Gingerol ameliorates alveolar hypercoagulation and fibrinolytic inhibition in LPS-provoked ARDS via RUNX1/NF-κB signaling pathway. Int. Immunopharmacol. 2024 128 111459 10.1016/j.intimp.2023.111459 38181675
    [Google Scholar]
  111. Preira P. Forel J.M. Robert P. Nègre P. Biarnes-Pelicot M. Xeridat F. Bongrand P. Papazian L. Theodoly O. The leukocyte-stiffening property of plasma in early acute respiratory distress syndrome (ARDS) revealed by a microfluidic single-cell study: The role of cytokines and protection with antibodies. Crit. Care 2016 20 1 8 10.1186/s13054‑015‑1157‑5 26757701
    [Google Scholar]
  112. Cesta M.C. Zippoli M. Marsiglia C. Gavioli E.M. Cremonesi G. Khan A. Mantelli F. Allegretti M. Balk R. Neutrophil activation and neutrophil extracellular traps (NETs) in COVID‐19 ARDS and immunothrombosis. Eur. J. Immunol. 2023 53 1 2250010 10.1002/eji.202250010 36239164
    [Google Scholar]
  113. Deng Z. Fan T. Xiao C. Tian H. Zheng Y. Li C. He J. TGF-β signaling in health, disease and therapeutics. Signal Transduct. Target. Ther. 2024 9 1 61 10.1038/s41392‑024‑01764‑w 38514615
    [Google Scholar]
  114. Paik S.S. Lee J.M. Ko I.G. Kim S.R. Kang S.W. An J. Kim J.A. Kim D. Hwang L. Jin J.J. Kim S.H. Cha J.Y. Choi C.W. Pirfenidone alleviates inflammation and fibrosis of acute respiratory distress syndrome by modulating the transforming growth factor-β/Smad signaling pathway. Int. J. Mol. Sci. 2024 25 15 8014 10.3390/ijms25158014 39125585
    [Google Scholar]
  115. Guan L. Yang H. Cai Y. Sun L. Di P. Li W. Liu G. Tang Y. ADMET-score: A comprehensive scoring function for evaluation of chemical drug-likeness. MedChemComm 2019 10 1 148 157 10.1039/C8MD00472B 30774861
    [Google Scholar]
  116. Hughes J.P. Rees S. Kalindjian S.B. Philpott K.L. Principles of early drug discovery. Br. J. Pharmacol. 2011 162 6 1239 1249 10.1111/j.1476‑5381.2010.01127.x 21091654
    [Google Scholar]
/content/journals/raiad/10.2174/0127722708368938250307071157
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Screening of Phytocompounds Against the NF-kB Pathway Genes and Lung Elevated Proteins Associated with Acute Respiratory Distress Syndrome
Bentham Science Publishers ; https://doi.org/10.2174/0127722708368938250307071157
/content/journals/raiad/10.2174/0127722708368938250307071157
/content/journals/raiad/10.2174/0127722708368938250307071157
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  • Article Type:     Research Article
Keywords: genkdaphine ; edulisin III ; Reactive oxygen species ; biomarker genes ; NF-kB ; PPI network ; acute respiratory distress syndrome

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