Skip to content
2000
image of Unlocking Toll-Like Receptors: Targeting Therapeutics for Respiratory Tract Infections and Inflammatory Disorders

Abstract

The Toll-like Receptors (TLRs) family has significantly enhanced the understanding of innate immune responses by identifying and responding to various microbes or host-derived organisms. TLRs contribute to these responses by increasing the levels of cytokines, interleukins, and other inflammatory mediators through multiple pathways. Located both intracellularly and on the surface of various cells and tissues, including vascular smooth muscles (VSMs) and myocardium cells, TLRs play distinct roles in innate immune activation, such as recognizing pathogen-associated molecular patterns (PAMPs) and activating downstream signaling pathways. In the context of COVID-19, TLRs are critically involved in the pathophysiology by mediating excessive inflammatory responses that exacerbate disease severity, influencing both the acute phase and long-term outcomes. It has been observed that inflammatory diseases such as atherosclerosis, viral myocarditis, and other comorbidities associated with the spread of COVID-19 have increased, although the exact mechanisms remain not fully understood. Nonetheless, there is evidence of TLR-mediated increased pro-inflammatory signaling by different mechanisms in these diseases. This review explains the role of TLRs in various inflammatory diseases related to COVID-19, including viral myocarditis, acute lung infections, and atherosclerosis. Furthermore, the review discusses various herbal drugs, such as and and their mechanisms of action on TLRs, including NF-κB, MyD88-dependent, MyD88-independent pathways, and Plasmacytoid DCs. Enhanced clarity on TLRs' specific contributions to COVID-19 pathophysiology and stronger evidence supporting herbal interventions targeting TLRs could improve the impact and applicability of these findings in clinical settings.

Loading

Article metrics loading...

/content/journals/raiad/10.2174/0127722708329138240926073013
2024-10-08
2024-10-22
Loading full text...

Full text loading...

References

  1. Vallejo J.G. Role of toll-like receptors in cardiovascular diseases. Clin. Sci. 2011 121 1 1 10 10.1042/CS20100539 21413930
    [Google Scholar]
  2. Xu M. Liu P.P. Li H. Innate immune signaling and its role in metabolic and cardiovascular diseases. Physiol. Rev. 2019 99 1 893 948 10.1152/physrev.00065.2017 30565509
    [Google Scholar]
  3. Ahmad R. Shihab P.K. Thomas R. Alghanim M. Hasan A. Sindhu S. Behbehani K. Increased expression of the interleukin-1 receptor-associated kinase (IRAK)-1 is associated with adipose tissue inflammatory state in obesity. Diabetol. Metab. Syndr. 2015 7 1 71 10.1186/s13098‑015‑0067‑7 26312071
    [Google Scholar]
  4. Sharma S. Garg I. Ashraf M.Z. TLR signalling and association of TLR polymorphism with cardiovascular diseases. Vascul. Pharmacol. 2016 87 30 37 10.1016/j.vph.2016.10.008 27826031
    [Google Scholar]
  5. Scheibner K.A. Lutz M.A. Boodoo S. Fenton M.J. Powell J.D. Horton M.R. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J. Immunol. 2006 177 2 1272 1281 10.4049/jimmunol.177.2.1272 16818787
    [Google Scholar]
  6. Frantz S. Ertl G. Bauersachs J. Mechanisms of disease: Toll-like receptors in cardiovascular disease. Nat. Clin. Pract. Cardiovasc. Med. 2007 4 8 444 454 10.1038/ncpcardio0938 17653117
    [Google Scholar]
  7. Zhou Y. Little P.J. Downey L. Afroz R. Wu Y. Ta H.T. Xu S. Kamato D. The role of toll-like receptors in atherothrombotic cardiovascular disease. ACS Pharmacol. Transl. Sci. 2020 3 3 457 471 10.1021/acsptsci.9b00100 32566912
    [Google Scholar]
  8. Dagenais G.R. Leong D.P. Rangarajan S. Lanas F. Lopez-Jaramillo P. Gupta R. Diaz R. Avezum A. Oliveira G.B.F. Wielgosz A. Parambath S.R. Mony P. Alhabib K.F. Temizhan A. Ismail N. Chifamba J. Yeates K. Khatib R. Rahman O. Zatonska K. Kazmi K. Wei L. Zhu J. Rosengren A. Vijayakumar K. Kaur M. Mohan V. Yusufali A. Kelishadi R. Teo K.K. Joseph P. Yusuf S. Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): A prospective cohort study. Lancet 2020 395 10226 785 794 10.1016/S0140‑6736(19)32007‑0 31492501
    [Google Scholar]
  9. Madan M. Amar S. Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: Proteomic findings. PLoS One 2008 3 9 e3204 10.1371/journal.pone.0003204 18787704
    [Google Scholar]
  10. Frazão J.B. Errante P.R. Condino-Neto A. Toll-like receptors’ pathway disturbances are associated with increased susceptibility to infections in humans. Arch. Immunol. Ther. Exp. 2013 61 6 427 443 10.1007/s00005‑013‑0243‑0 24057516
    [Google Scholar]
  11. Wicherska-Pawłowska K. Wróbel T. Rybka J. Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) in innate immunity. TLRs, NLRs, and RLRs ligands as immunotherapeutic agents for hematopoietic diseases. Int. J. Mol. Sci. 2021 22 24 13397 10.3390/ijms222413397 34948194
    [Google Scholar]
  12. Medzhitov R. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 2001 1 2 135 145 10.1038/35100529 11905821
    [Google Scholar]
  13. de Vicente L.G. Pinto A.P. da Rocha A.L. Pauli J.R. de Moura L.P. Cintra D.E. Ropelle E.R. da Silva A.S.R. Role of TLR4 in physical exercise and cardiovascular diseases. Cytokine 2020 136 155273 10.1016/j.cyto.2020.155273 32932194
    [Google Scholar]
  14. Frantz S. Bauersachs J. Kelly R. Innate immunity and the heart. Curr. Pharm. Des. 2005 11 10 1279 1290 10.2174/1381612053507512 15853684
    [Google Scholar]
  15. Vina J. Sanchis-Gomar F. Martinez-Bello V. Gomez-Cabrera M.C. Exercise acts as a drug; The pharmacological benefits of exercise. Br. J. Pharmacol. 2012 167 1 1 12 10.1111/j.1476‑5381.2012.01970.x 22486393
    [Google Scholar]
  16. Narayanan K.B. Park H.H. Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways. Apoptosis 2015 20 2 196 209 10.1007/s10495‑014‑1073‑1 25563856
    [Google Scholar]
  17. O’Neill L.A.J. Bowie A.G. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 2007 7 5 353 364 10.1038/nri2079 17457343
    [Google Scholar]
  18. Medzhitov R. Preston-Hurlburt P. Kopp E. Stadlen A. Chen C. Ghosh S. Janeway C.A. Jr MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol. Cell 1998 2 2 253 258 10.1016/S1097‑2765(00)80136‑7 9734363
    [Google Scholar]
  19. Vilahur G. Badimon L. Ischemia/reperfusion activates myocardial innate immune response: The key role of the toll-like receptor. Front. Physiol. 2014 5 496 10.3389/fphys.2014.00496 25566092
    [Google Scholar]
  20. Frantz S. Kobzik L. Kim Y.D. Fukazawa R. Medzhitov R. Lee R.T. Kelly R.A. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J. Clin. Invest. 1999 104 3 271 280 10.1172/JCI6709 10430608
    [Google Scholar]
  21. Wright S.D. Toll, a new piece in the puzzle of innate immunity. J. Exp. Med. 1999 189 4 605 609 10.1084/jem.189.4.605 9989974
    [Google Scholar]
  22. Kawasaki T. Kawai T. Toll-like receptor signaling pathways. Front. Immunol. 2014 5 461 10.3389/fimmu.2014.00461 25309543
    [Google Scholar]
  23. Saleh H.A. Yousef M.H. Abdelnaser A. The anti-inflammatory properties of phytochemicals and their effects on epigenetic mechanisms involved in TLR4/NF-κB-mediated inflammation. Front. Immunol. 2021 12 606069 10.3389/fimmu.2021.606069 33868227
    [Google Scholar]
  24. Mullick A.E. Soldau K. Kiosses W.B. Bell T.A. III Tobias P.S. Curtiss L.K. Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events. J. Exp. Med. 2008 205 2 373 383 10.1084/jem.20071096 18250194
    [Google Scholar]
  25. Singh M.V. Cicha M.Z. Nunez S. Meyerholz D.K. Chapleau M.W. Abboud F.M. Angiotensin II-induced hypertension and cardiac hypertrophy are differentially mediated by TLR3- and TLR4-dependent pathways. Am. J. Physiol. Heart Circ. Physiol. 2019 316 5 H1027 H1038 10.1152/ajpheart.00697.2018 30793936
    [Google Scholar]
  26. Ogus A.C. Yoldas B. Ozdemir T. Uguz A. Olcen S. Keser I. Coskun M. Cilli A. Yegin O. The Arg753Gln polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur. Respir. J. 2004 23 2 219 223 10.1183/09031936.03.00061703 14979495
    [Google Scholar]
  27. Müller M. Scheel O. Lindner B. Gutsmann T. Seydel U. The role of membrane-bound LBP, endotoxin aggregates, and the MaxiK channel in LPS-induced cell activation. J. Endotoxin Res. 2003 9 3 181 186 10.1177/09680519030090030701 12831460
    [Google Scholar]
  28. Kapelouzou A. Giaglis S. Peroulis M. Katsimpoulas M. Moustardas P. Aravanis C.V. Kostakis A. Karayannakos P.E. Cokkinos D.V. Overexpression of toll-like receptors 2, 3, 4, and 8 is correlated to the vascular atherosclerotic process in the hyperlipidemic rabbit model: the effect of statin treatment. J. Vasc. Res. 2017 54 3 156 169 10.1159/000457797 28478461
    [Google Scholar]
  29. Gorbea C. Makar K.A. Pauschinger M. Pratt G. Bersola J.L.F. Varela J. David R.M. Banks L. Huang C.H. Li H. Schultheiss H.P. Towbin J.A. Vallejo J.G. Bowles N.E. A role for Toll-like receptor 3 variants in host susceptibility to enteroviral myocarditis and dilated cardiomyopathy. J. Biol. Chem. 2010 285 30 23208 23223 10.1074/jbc.M109.047464 20472559
    [Google Scholar]
  30. Ishibashi M. Sayers S. D’Armiento J.M. Tall A.R. Welch C.L. TLR3 deficiency protects against collagen degradation and medial destruction in murine atherosclerotic plaques. Atherosclerosis 2013 229 1 52 61 10.1016/j.atherosclerosis.2013.03.035 23676255
    [Google Scholar]
  31. Ameziane N. Beillat T. Verpillat P. Chollet-Martin S. Aumont M.C. Seknadji P. Lamotte M. Lebret D. Ollivier V. de Prost D. Association of the Toll-like receptor 4 gene Asp299Gly polymorphism with acute coronary events. Arterioscler. Thromb. Vasc. Biol. 2003 23 12 e61 e64 10.1161/01.ATV.0000101191.92392.1D 14563652
    [Google Scholar]
  32. Miller Y.I. Choi S.H. Wiesner P. Bae Y.S. The SYK side of TLR4: Signalling mechanisms in response to LPS and minimally oxidized LDL. Br. J. Pharmacol. 2012 167 5 990 999 10.1111/j.1476‑5381.2012.02097.x 22776094
    [Google Scholar]
  33. Koulis C. Chen Y.C. Hausding C. Ahrens I. Kyaw T.S. Tay C. Allen T. Jandeleit-Dahm K. Sweet M.J. Akira S. Bobik A. Peter K. Agrotis A. Protective role for Toll-like receptor-9 in the development of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 2014 34 3 516 525 10.1161/ATVBAHA.113.302407 24436372
    [Google Scholar]
  34. Zhang Y. Zhang Y. Pterostilbene, a novel natural plant conduct, inhibits high fat-induced atherosclerosis inflammation via NF-κB signaling pathway in Toll-like receptor 5 (TLR5) deficient mice. Biomed. Pharmacother. 2016 81 345 355 10.1016/j.biopha.2016.04.031 27261612
    [Google Scholar]
  35. Fu Y. Hu X. Cao Y. Zhang Z. Zhang N. Saikosaponin a inhibits lipopolysaccharide-oxidative stress and inflammation in Human umbilical vein endothelial cells via preventing TLR4 translocation into lipid rafts. Free Radic. Biol. Med. 2015 89 777 785 10.1016/j.freeradbiomed.2015.10.407 26475038
    [Google Scholar]
  36. Kim J. Yoo J.Y. Suh J.M. Park S. Kang D. Jo H. Bae Y.S. The flagellin-TLR5-Nox4 axis promotes the migration of smooth muscle cells in atherosclerosis. Exp. Mol. Med. 2019 51 7 1 13 10.1038/s12276‑019‑0275‑6 31292433
    [Google Scholar]
  37. Lee Y.H. Bae S.C. Kim J.H. Song G.G. Toll-like receptor polymorphisms and rheumatoid arthritis: A systematic review. Rheumatol. Int. 2014 34 1 111 116 10.1007/s00296‑013‑2666‑7 23325096
    [Google Scholar]
  38. Sales M.L. Schreiber R. Ferreira-Sae M.C.S. Fernandes M.N. Piveta C.S.C. Cipolli J.A.A. Cardoso C.C. Matos-Souza J.R. Geloneze B. Franchini K.G. Nadruz W. Jr Toll-like receptor 6 Ser249Pro polymorphism is associated with lower left ventricular wall thickness and inflammatory response in hypertensive women. Am. J. Hypertens. 2010 23 6 649 654 10.1038/ajh.2010.24 20224557
    [Google Scholar]
  39. Hamann L. Koch A. Sur S. Hoefer N. Glaeser C. Schulz S. Gross M. Franke A. Nöthlings U. Zacharowski K. Schumann R.R. Association of a common TLR-6 polymorphism with coronary artery disease – Implications for healthy ageing? Immun. Ageing 2013 10 1 43 10.1186/1742‑4933‑10‑43 24498948
    [Google Scholar]
  40. Ha T. Liu L. Kelley J. Kao R. Williams D. Li C. Toll-like receptors: New players in myocardial ischemia/reperfusion injury. Antioxid. Redox Signal. 2011 15 7 1875 1893 10.1089/ars.2010.3723 21091074
    [Google Scholar]
  41. Brea D. Sobrino T. Rodríguez-Yáñez M. Ramos-Cabrer P. Agulla J. Rodríguez-González R. Campos F. Blanco M. Castillo J. Toll-like receptors 7 and 8 expression is associated with poor outcome and greater inflammatory response in acute ischemic stroke. Clin. Immunol. 2011 139 2 193 198 10.1016/j.clim.2011.02.001 21354862
    [Google Scholar]
  42. Baxan N. Papanikolaou A. Salles-Crawley I. Lota A. Chowdhury R. Dubois O. Branca J. Hasham M.G. Rosenthal N. Prasad S.K. Zhao L. Harding S.E. Sattler S. Characterization of acute TLR-7 agonist-induced hemorrhagic myocarditis in mice by multiparametric quantitative cardiac magnetic resonance imaging. Dis. Model. Mech. 2019 12 8 dmm040725 10.1242/dmm.040725 31324689
    [Google Scholar]
  43. Zhang Q. Raoof M. Chen Y. Sumi Y. Sursal T. Junger W. Brohi K. Itagaki K. Hauser C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 2010 464 7285 104 107 10.1038/nature08780 20203610
    [Google Scholar]
  44. Heil F. Hemmi H. Hochrein H. Ampenberger F. Kirschning C. Akira S. Lipford G. Wagner H. Bauer S. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004 303 5663 1526 1529 10.1126/science.1093620 14976262
    [Google Scholar]
  45. Cole JE Georgiou E Monaco C The expression and functions of toll-like receptors in atherosclerosis. Mediators Inflamm 2010 2010 393946 10.1155/2010/393946
    [Google Scholar]
  46. Niessner A. Sato K. Chaikof E.L. Colmegna I. Goronzy J.J. Weyand C.M. Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-α. Circulation 2006 114 23 2482 2489 10.1161/CIRCULATIONAHA.106.642801 17116765
    [Google Scholar]
  47. Guiducci C. Coffman R.L. Barrat F.J. Signalling pathways leading to IFN‐α production in human plasmacytoid dendritic cell and the possible use of agonists or antagonists of TLR7 and TLR9 in clinical indications. J. Intern. Med. 2009 265 1 43 57 10.1111/j.1365‑2796.2008.02050.x 19093959
    [Google Scholar]
  48. Saber M.M. Monir N. Awad A.S. Elsherbiny M.E. Zaki H.F. TLR9: A friend or a foe. Life Sci. 2022 307 120874 10.1016/j.lfs.2022.120874 35963302
    [Google Scholar]
  49. Root-Bernstein R. Innate receptor activation patterns involving TLR and NLR synergisms in COVID-19, ALI/ARDS and sepsis cytokine storms: A review and model making novel predictions and therapeutic suggestions. Int. J. Mol. Sci. 2021 22 4 2108 10.3390/ijms22042108 33672738
    [Google Scholar]
  50. Khanmohammadi S. Rezaei N. Role of Toll‐like receptors in the pathogenesis of COVID‐19. J. Med. Virol. 2021 93 5 2735 2739 10.1002/jmv.26826 33506952
    [Google Scholar]
  51. Rai SN Tiwari N Singh P Singh AK Mishra D Imran M Exploring the paradox of covid-19 in neurological complications with emphasis on parkinson’s and alzheimer’s disease. Oxid Med Cell Longev 2022 2022
    [Google Scholar]
  52. Jing H. Chen X. Zhang S. Liu H. Zhang C. Du J. Li Y. Wu X. Li M. Xiang M. Liu L. Shi J. Neutrophil extracellular traps (NETs): The role of inflammation and coagulation in COVID-19. Am. J. Transl. Res. 2021 13 8 8575 8588 34539980
    [Google Scholar]
  53. Youness A. Cenac C. Faz-López B. Grunenwald S. Barrat F.J. Chaumeil J. Mejía J.E. Guéry J.C. TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells. Biol. Sex Differ. 2023 14 1 60 10.1186/s13293‑023‑00544‑5 37723501
    [Google Scholar]
  54. Jiang Y. Zhao T. Zhou X. Xiang Y. Gutierrez-Castrellon P. Ma X. Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions. MedComm 2022 3 3 e154 10.1002/mco2.154 35923762
    [Google Scholar]
  55. Xiang M Fan J Fan J. Association of Toll-like receptor signaling and reactive oxygen species: a potential therapeutic target for posttrauma acute lung injury. Mediators Inflamm 2010 2010 10.1155/2010/916425
    [Google Scholar]
  56. Sahu A. Rathee S. Jain S.K. Patil U.K. Exploring the promising role of guggulipid in rheumatoid arthritis management: An in-depth analysis. Curr. Rheumatol. Rev. 2024 20 5 469 487 10.2174/0115733971280984240101115203 38284718
    [Google Scholar]
  57. Jiang H. Xu H. Jiang H. Zhang Y. Sun Y. The role of TLR4 in the pathogenesis of indirect acute lung injury. Front. Biosci. 2013 18 4 1244 1255 10.2741/4176 23747880
    [Google Scholar]
  58. Thiriet M. Thiriet M. Hyperlipidemias and obesity. Vasculopathies: Behavioral. Chemical, Environmental, and Genetic Factors Springer 2018 331 548
    [Google Scholar]
  59. Ammirati E. Frigerio M. Adler E.D. Basso C. Birnie D.H. Brambatti M. Friedrich M.G. Klingel K. Lehtonen J. Moslehi J.J. Pedrotti P. Rimoldi O.E. Schultheiss H.P. Tschöpe C. Cooper L.T. Jr Camici P.G. Management of acute myocarditis and chronic inflammatory cardiomyopathy: An expert consensus document. Circ. Heart Fail. 2020 13 11 e007405 10.1161/CIRCHEARTFAILURE.120.007405 33176455
    [Google Scholar]
  60. Kemball C.C. Fujinami R.S. Whitton J.L. Adaptive immune responses. The Picornaviruses 2010 303 319
    [Google Scholar]
  61. Yajima T. Knowlton K.U. Viral Myocarditis. Circulation 2009 119 19 2615 2624 10.1161/CIRCULATIONAHA.108.766022 19451363
    [Google Scholar]
  62. Frantz S. Falcao-Pires I. Balligand J.L. Bauersachs J. Brutsaert D. Ciccarelli M. Dawson D. de Windt L.J. Giacca M. Hamdani N. Hilfiker-Kleiner D. Hirsch E. Leite-Moreira A. Mayr M. Thum T. Tocchetti C.G. van der Velden J. Varricchi G. Heymans S. The innate immune system in chronic cardiomyopathy: A European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC. Eur. J. Heart Fail. 2018 20 3 445 459 10.1002/ejhf.1138 29333691
    [Google Scholar]
  63. Tam P.E. Coxsackievirus myocarditis: Interplay between virus and host in the pathogenesis of heart disease. Viral Immunol. 2006 19 2 133 146 10.1089/vim.2006.19.133 16817756
    [Google Scholar]
  64. Xia L. Oyang L. Lin J. Tan S. Han Y. Wu N. Yi P. Tang L. Pan Q. Rao S. Liang J. Tang Y. Su M. Luo X. Yang Y. Shi Y. Wang H. Zhou Y. Liao Q. The cancer metabolic reprogramming and immune response. Mol. Cancer 2021 20 1 28 10.1186/s12943‑021‑01316‑8 33546704
    [Google Scholar]
  65. Harris S.M. Harvey E.J. Hughes T.R. Ramji D.P. The interferon-γ-mediated inhibition of lipoprotein lipase gene transcription in macrophages involves casein kinase 2- and phosphoinositide-3-kinase-mediated regulation of transcription factors Sp1 and Sp3. Cell. Signal. 2008 20 12 2296 2301 10.1016/j.cellsig.2008.08.016 18793716
    [Google Scholar]
  66. Khakpour S. Wilhelmsen K. Hellman J. Vascular endothelial cell Toll-like receptor pathways in sepsis. Innate Immun. 2015 21 8 827 846 10.1177/1753425915606525 26403174
    [Google Scholar]
  67. Wu X. Iroegbu C.D. Peng J. Guo J. Yang J. Fan C. Cell death and exosomes regulation after myocardial infarction and ischemia-reperfusion. Front. Cell Dev. Biol. 2021 9 673677 10.3389/fcell.2021.673677 34179002
    [Google Scholar]
  68. Hu C. Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J. Cell. Mol. Med. 2018 22 3 1428 1442 10.1111/jcmm.13492 29392844
    [Google Scholar]
  69. Singhai H. Rathee S. Jain S.K. Patil U.K. The potential of natural products in the management of cardiovascular disease. Curr. Pharm. Des. 2024 30 8 624 638 10.2174/0113816128295053240207090928 38477208
    [Google Scholar]
  70. Evaristo-Mendonça F Sardella-Silva G Kasai-Brunswick TH Campos RMP Domizi P Santiago MF Preconditioning of rat bone marrow-derived Mesenchymal stromal cells with toll-like receptor agonists. Stem Cells Int 2019 2019 10.1155/2019/7692973
    [Google Scholar]
  71. De Meyer S.F. Savchenko A.S. Haas M.S. Schatzberg D. Carroll M.C. Schiviz A. Dietrich B. Rottensteiner H. Scheiflinger F. Wagner D.D. Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice. Blood 2012 120 26 5217 5223 10.1182/blood‑2012‑06‑439935 22915644
    [Google Scholar]
  72. Koushki K. Shahbaz S.K. Mashayekhi K. Sadeghi M. Zayeri Z.D. Taba M.Y. Banach M. Al-Rasadi K. Johnston T.P. Sahebkar A. Anti-inflammatory action of statins in cardiovascular disease: The role of inflammasome and toll-like receptor pathways. Clin. Rev. Allergy Immunol. 2021 60 2 175 199 10.1007/s12016‑020‑08791‑9 32378144
    [Google Scholar]
  73. Liu X. Zheng J. Zhou H. TLRs as pharmacological targets for plant-derived compounds in infectious and inflammatory diseases. Int. Immunopharmacol. 2011 11 10 1451 1456 10.1016/j.intimp.2011.04.027 21586344
    [Google Scholar]
  74. Rathee S. Patil U.K. Jain S.K. Exploring the potential of dietary phytochemicals in cancer prevention: A comprehensive review. J. Explor. Res. Pharmacol. 2024 9 1 51 64 10.14218/JERP.2023.00050
    [Google Scholar]
  75. Choi C.Y. Kim J.Y. Kim Y.S. Chung Y.C. Seo J.K. Jeong H.G. Aqueous extract isolated from Platycodon grandiflorum elicits the release of nitric oxide and tumor necrosis factor-α from murine macrophages. Int. Immunopharmacol. 2001 1 6 1141 1151 10.1016/S1567‑5769(01)00047‑9 11407308
    [Google Scholar]
  76. Öberg F. Haseeb A. Ahnfelt M. Pontén F. Westermark B. El-Obeid A. Herbal melanin activates TLR4/NF-κB signaling pathway. Phytomedicine 2009 16 5 477 484 10.1016/j.phymed.2008.10.008 19103478
    [Google Scholar]
  77. Chahal D.S. Sivamani R.K. Rivkah Isseroff R. Dasu M.R. Plant-based modulation of Toll-like receptors: An emerging therapeutic model. Phytother. Res. 2013 27 10 1423 1438 10.1002/ptr.4886 23147906
    [Google Scholar]
  78. Kidd P.M. Bioavailability and activity of phytosome complexes from botanical polyphenols: The silymarin, curcumin, green tea, and grape seed extracts. Altern. Med. Rev. 2009 14 3 226 246 19803548
    [Google Scholar]
  79. Shitan N. Yazaki K. Accumulation and membrane transport of plant alkaloids. Curr. Pharm. Biotechnol. 2007 8 4 244 252 10.2174/138920107781387429 17691993
    [Google Scholar]
  80. Manikishore M. Maurya S.K. Rathee S. Patil U.K. Genome editing approaches using zinc finger nucleases (ZFNs) for the treatment of motor neuron diseases. Curr. Pharm. Biotechnol. 2024 25 10.2174/0113892010307288240526071810 38847163
    [Google Scholar]
  81. Verstak B. Hertzog P. Mansell A. Toll-like receptor signalling and the clinical benefits that lie within. Inflamm. Res. 2007 56 1 1 10 10.1007/s00011‑007‑6093‑7 17334664
    [Google Scholar]
  82. Sen D. Rathee S. Pandey V. Jain S.K. Patil U.K. Comprehensive insights into pathophysiology of alzheimer’s disease: Herbal approaches for mitigating neurodegeneration. Curr. Alzheimer Res. 2024 10.2174/0115672050309057240404075003 38623983
    [Google Scholar]
/content/journals/raiad/10.2174/0127722708329138240926073013
Loading
/content/journals/raiad/10.2174/0127722708329138240926073013
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test