β-D-mannuronic Acid (M2000) and Inflammatory Cytokines in COVID-19; An In vitro Study
-
Behrouz Robat-Jazi
,
Khodayar Ghorban
,
Mohammad Gholami
,
Esmaeil Samizadeh
,
Zahra Aghazadeh
,
Mohammad Amin Shahrbaf
,
Maryam Dadmanesh
,
Negin Hosseini Rouzbahani
,
Abbas Mirshafiey
Abstract
coronavirus disease of 2019 (COVID-19) can be complicated by acute respiratory distress syndrome (ARDS) and may be associated with cytokine storm and multiorgan failure. Anti-inflammatory agents, such as systemic corticosteroids, monoclonal antibodies, and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used for this purpose. In this study, we evaluated the immunomodulatory effect of mannuronic acid (M2000), which is a novel NSAID, on COVID-19-related cytokine storms.
This study was conducted in vitro on blood samples of 30 COVID-19 patients who presented with ARDS to a referral center. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and incubated with phorbol myristate acetate for 24 hours. M2000 was administered with the dosages of 25 µg/well and 50 µg/well after 4 hours of incubation at 37°C. The quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess mRNA gene expression. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the supernatant PBMC levels of interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ.
Both mRNA expression and the supernatant PBMC levels of IL-17, TNF-α, IL‑6, and IFN‑γ were decreased in PBMCs of COVID-19 patients treated with M2000 compared with the control group.
For the first time, it was observed that M2000 could be effective in alleviating the inflammatory cascade of COVID-19 patients based on an in vitro model. After further studies in vitro and in animal models, M2000 could be considered a novel NSAID drug in COVID-19 patients.
1. Shahrbaf MA, Tabary M, Khaheshi I. The right ventricle in COVID-19 patients. Eur Heart J. 2021;42(6):559-60.
2. Shahrbaf MA, Hassan M, Vosough M. COVID-19 and hygiene hypothesis: increment of the inflammatory bowel diseases in next generation? Expert Rev Gastroenterol Hepatol. 2021:1-3.
3. Shahrbaf MA, Tabary M, Khaheshi I. Cardiovascular considerations of Remdesivir and Favipiravir in the treatment of COVID-19. Cardiovasc Hematol Disord Drug Targets. 2021;21(2):88-90.
4. Barekat M, Shahrbaf MA, Rahi K, Vosough M. Hypertension in COVID-19, A Risk Factor for Infection or A Late Consequence? Cell J. 2022;24(7):424-6.
5. Hazrati E, Gholami M, Farahani RH, Ghorban K, Ghayomzadeh M, Rouzbahani NH. The effect of IGF-1 plasma concentration on COVID-19 severity. Microb Pathog. 2022;164:105416.
6. Farahani RH, Gholami M, Hazrati E, Rouzbahani NH, Hejripour Z, Soleiman-Meigooni S, et al. Clinical features of ICU admitted and intubated novel corona virus-infected patients in Iran. Arch Clin Infect Dis. 2020;15(2).
7. WHO Coronavirus (COVID-19) Dashboard 19 October 2022 [Available from: https://covid19.who.int/.
8. Hossein-Khannazer N, Shokoohian B, Shpichka A, Aghdaei HA, Timashev P, Vosough M. An update to "novel therapeutic approaches for treatment of COVID-19". J Mol Med. 2021;99(2):303-10.
9. Kumar M, Al Khodor S. Pathophysiology and treatment strategies for COVID-19. J Transl Med. 2020;18(1):353.
10. Parasher A. COVID-19: Current understanding of its Pathophysiology, Clinical presentation and Treatment. Postgrad Med J. 2021;97(1147):312-20.
11. Singh SP, Pritam M, Pandey B, Yadav TP. Microstructure, pathophysiology, and potential therapeutics of COVID-19: A comprehensive review. J Med Virol. 2021;93(1):275-99.
12. Hasan SS, Capstick T, Ahmed R, Kow CS, Mazhar F, Merchant HA, et al. Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. Expert Rev Respir Med. 2020;14(11):1149-63.
13. Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J Mol Histol. 2020;51(6):613-28.
14. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol. 2020;214(12):108393.
15. Kelleni MT. Early use of non-steroidal anti-inflammatory drugs in COVID-19 might reverse pathogenesis, prevent complications and improve clinical outcomes. Biomed Pharmacother. 2021;133(6):110982.
16. Mirshafiey A, Taeb M, Mortazavi-Jahromi SS, Jafarnezhad-Ansariha F, Rehm BHA, Esposito E, et al. Introduction of β-d-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property based on COX-1/COX-2 activity and gene expression. Pharmacol Rep. 2017;69(5):1067-72.
17. Jafarnezhad-Ansariha F, Yekaninejad MS, Jamshidi AR, Mansouri R, Vojdanian M, Mahmoudi M, et al. The effects of β-D-mannuronic acid (M2000), as a novel NSAID, on COX1 and COX2 activities and gene expression in ankylosing spondylitis patients and the murine monocyte/macrophage, J774 cell line. Inflammopharmacology. 2018;26(2):375-84.
18. Fattahi MJ, Abdollahi M, Agha Mohammadi A, Rastkari N, Khorasani R, Ahmadi H, et al. Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug. Immunopharmacol Immunotoxicol. 2015;37(6):535-40.
19. Mortazavi-Jahromi SS, Jamshidi MM, Farazmand A, Aghazadeh Z, Yousefi M, Mirshafiey A. Pharmacological effects of β-D-mannuronic acid (M2000) on miR-146a, IRAK1, TRAF6 and NF-κB gene expression, as target molecules in inflammatory reactions. Pharmacol Rep. 2017;69(3):479-84.
20. Fard NA, Tabrizian N, Mirzaei R, Motamed N, Zavareh FT, Mirshafiey A. The Safety Property of β-D-Mannuronic Acid (M2000) as a Novel Immunosuppressive Agent on Differentiation, Maturation and Function of Human Dendritic Cells. Curr Drug Discov Technol. 2016;13(3):164-9.
21. Aletaha S, Haddad L, Roozbehkia M, Bigdeli R, Asgary V, Mahmoudi M, et al. M2000 (β-D-Mannuronic Acid) as a Novel Antagonist for Blocking the TLR2 and TLR4 Downstream Signalling Pathway. Scand J Immunol. 2017;85(2):122-9.
22. Aslani M, Ahmadzadeh A, Aghazadeh Z, Zaki-Dizaji M, Sharifi L, Hosseini M, et al. Influence of β-D-mannuronic Acid, as a New Member of Non-steroidal Anti- Inflammatory Drugs Family, on the Expression Pattern of Chemokines and their Receptors in Rheumatoid Arthritis. Curr Drug Discov Technol. 2021;18(1):65-74.
23. Fanelli V, Vlachou A, Ghannadian S, Simonetti U, Slutsky AS, Zhang H. Acute respiratory distress syndrome: new definition, current and future therapeutic options. J Thorac Dis. 2013;5(3):326-34.
24. Fuss IJ, Kanof ME, Smith PD, Zola H. Isolation of whole mononuclear cells from peripheral blood and cord blood. Curr Protoc Immunol. 2009;Chapter 7:Unit7.1.
25. Valizadeh H, Abdolmohammadi-Vahid S, Danshina S, Ziya Gencer M, Ammari A, Sadeghi A, et al. Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients. Int Immunopharmacol. 2020;89(Pt B):107088.
26. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
27. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74.
28. Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. 2022;23(1):3-20.
29. Darif D, Hammi I, Kihel A, El Idrissi Saik I, Guessous F, Akarid K. The proinflammatory cytokines in COVID-19 pathogenesis: What goes wrong? Microb Pathog. 2021;153:104799-.
30. Fara A, Mitrev Z, Rosalia RA, Assas BM. Cytokine storm and COVID-19: a chronicle of proinflammatory cytokines. Open Biol. 2020;10(9):200160.
31. Hussman JP. Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention. Front Pharmacol. 2020;11:1169.
32. Yang L, Xie X, Tu Z, Fu J, Xu D, Zhou Y. The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduct Target Ther. 2021;6(1):255.
33. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev. 2020;7(6):998-1002.
34. Mantovani S, Daga S, Fallerini C, Baldassarri M, Benetti E, Picchiotti N, et al. Rare variants in Toll-like receptor 7 results in functional impairment and downregulation of cytokine-mediated signaling in COVID-19 patients. Genes Immun. 2022;23(1):51-6.
35. Li W, Qiao J, You Q, Zong S, Peng Q, Liu Y, et al. SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS. Front immunol. 2021;12.
36. de Queiroz TM, Lakkappa N, Lazartigues E. ADAM17-Mediated Shedding of Inflammatory Cytokines in Hypertension. Front Pharmacol. 2020;11:1154.
37. Aslani M, Mortazavi-Jahromi SS, Mirshafiey A. Cytokine storm in the pathophysiology of COVID-19: Possible functional disturbances of miRNAs. Int Immunopharmacol. 2021;101(Pt A):108172.
38. Johnson DE, O'Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15(4):234-48.
39. Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021;33(3):127-48.
40. Puccetti M, Costantini C, Ricci M, Giovagnoli S. Tackling Immune Pathogenesis of COVID-19 through Molecular Pharmaceutics. Pharmaceutics. 2021;13(4).
41. Kragholm K, Torp-Pedersen C, Fosbol E. Non-steroidal anti-inflammatory drug use in COVID-19. Lancet Rheumatol. 2021;3(7):e465-e6.
42. Zhou Q, Zhao S, Gan L, Wang Z, Peng S, Li Q, et al. Use of non-steroidal anti-inflammatory drugs and adverse outcomes during the COVID-19 pandemic: A systematic review and meta-analysis. EClinicalMedicine. 2022;46:101373.
43. Reese JT, Coleman B, Chan L, Blau H, Callahan TJ, Cappelletti L, et al. NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study. J Virol. 2022;19(1):84.
44. Seifirad S. Pirfenidone: A novel hypothetical treatment for COVID-19. Med Hypotheses. 2020;144:110005.
45. Rogero MM, Leão MC, Santana TM, Pimentel M, Carlini GCG, da Silveira TFF, et al. Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19. Free Radic Biol Med. 2020;156:190-9.
46. Wang R. Etoricoxib may inhibit cytokine storm to treat COVID-19. Med Hypotheses. 2021;150(14):110557.
47. Rehan M, Ahmed F, Howladar SM, Refai MY, Baeissa HM, Zughaibi TA, et al. A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm. Front Immunol. 2021;12:648250.
48. Bahbah EI, Negida A, Nabet MS. Purposing Saikosaponins for the treatment of COVID-19. Med Hypotheses. 2020;140:109782.
49. Raciti L, De Luca R, Raciti G, Arcadi FA, Calabrò RS. The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study. Med Sci (Basel). 2022;10(3).
50. Marinella MA. Indomethacin and resveratrol as potential treatment adjuncts for SARS-CoV-2/COVID-19. Int J Clin Pract. 2020;74(9):e13535.
51. Mirshafiey A, Cuzzocrea S, Rehm BH, Matsuo H. M2000: a revolution in pharmacology. Med Sci Monit. 2005;11(8):Pi53-63.
52. M MF, Motevaseli E, Maghsood F, Heidari-Kharaji M, Mirshafiey A. Anti-inflammatory Property of β-D-Mannuronic Acid (M2000) on Expression and Activity of Matrix Metalloproteinase-2 and -9 through CD147 Molecule in Phorbol Myristate Acetate-differentiated THP-1 Cells. Iran J Allergy Asthma Immunol. 2017;16(5):443-51.
53. Ahmadi H, Jamshidi AR, Mahmoudi M, Cuzzocrea S, Fattahi MJ, Barati A, et al. The Potent Inhibitory Effect of β-D-Mannuronic Acid (M2000) as a Novel NSAID with Immunosuppressive Property on Anti-Cyclic Citrullinated Peptide Antibodies, Rheumatoid Factor and Anti-dsDNA Antibodies in Patients with Rheumatoid Arthritis. Curr Drug Discov Technol. 2017;14(3):206-14.
54. Ahmadi H, Jamshidi AR, Gharibdoost F, Mahmoudi M, Rastkari N, Mostafaei S, et al. A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of β-D-mannuronic acid in rheumatoid arthritis patients. Inflammopharmacology. 2018;26(3):737-45.
55. Rezaieyazdi Z, Farooqi A, Soleymani-Salehabadi H, Ahmadzadeh A, Aslani M, Omidian S, et al. International multicenter randomized, placebo-controlled phase III clinical trial of β-D-mannuronic acid in rheumatoid arthritis patients. Inflammopharmacology. 2019;27(5):911-21.
56. Ahmadi H, Mahmoudi M, Gharibdoost F, Vojdanian M, Jamshidi AR, Fattahi MJ, et al. Targeting of circulating Th17 cells by β-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis. Inflammopharmacology. 2018;26(1):57-65.
57. Gaafar NAG, Aslani M, Aghazadeh Z, Razavi A, Mirshafiey A. The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients. Curr Drug Discov Technol. 2020;17(5):704-10.
58. Gaafar NAG, Aslani M, Aghazadeh Z, Mortazavi-Jahromi SS, Razavi A, Mirshafiey A. Effects of mannuronic acid (M2000) on gene expression profile of signal transducer and activator of transcription proteins (STATs) in rheumatoid arthritis patients. Reumatismo. 2020;72(2):93-102.
59. Mortazavi-Jahromi SS, Ahmadzadeh A, Rezaieyazdi Z, Aslani M, Omidian S, Mirshafiey A. The role of β-d-mannuronic acid, as a new non-steroidal anti-inflammatory drug on expression of miR-146a, IRAK1, TRAF6, NF-κB and proinflammatory cytokines following a clinical trial in rheumatoid arthritis patients. Immunopharmacol Immunotoxicol. 2020;42(3):228-36.
60. del Valle-Mendoza J, Tarazona-Castro Y, Merino-Luna A, Carrillo-Ng H, Kym S, Aguilar-Luis MA, et al. Comparison of cytokines levels among COVID-19 patients living at sea level and high altitude. BMC Infect Dis. 2022;22(1):96.
2. Shahrbaf MA, Hassan M, Vosough M. COVID-19 and hygiene hypothesis: increment of the inflammatory bowel diseases in next generation? Expert Rev Gastroenterol Hepatol. 2021:1-3.
3. Shahrbaf MA, Tabary M, Khaheshi I. Cardiovascular considerations of Remdesivir and Favipiravir in the treatment of COVID-19. Cardiovasc Hematol Disord Drug Targets. 2021;21(2):88-90.
4. Barekat M, Shahrbaf MA, Rahi K, Vosough M. Hypertension in COVID-19, A Risk Factor for Infection or A Late Consequence? Cell J. 2022;24(7):424-6.
5. Hazrati E, Gholami M, Farahani RH, Ghorban K, Ghayomzadeh M, Rouzbahani NH. The effect of IGF-1 plasma concentration on COVID-19 severity. Microb Pathog. 2022;164:105416.
6. Farahani RH, Gholami M, Hazrati E, Rouzbahani NH, Hejripour Z, Soleiman-Meigooni S, et al. Clinical features of ICU admitted and intubated novel corona virus-infected patients in Iran. Arch Clin Infect Dis. 2020;15(2).
7. WHO Coronavirus (COVID-19) Dashboard 19 October 2022 [Available from: https://covid19.who.int/.
8. Hossein-Khannazer N, Shokoohian B, Shpichka A, Aghdaei HA, Timashev P, Vosough M. An update to "novel therapeutic approaches for treatment of COVID-19". J Mol Med. 2021;99(2):303-10.
9. Kumar M, Al Khodor S. Pathophysiology and treatment strategies for COVID-19. J Transl Med. 2020;18(1):353.
10. Parasher A. COVID-19: Current understanding of its Pathophysiology, Clinical presentation and Treatment. Postgrad Med J. 2021;97(1147):312-20.
11. Singh SP, Pritam M, Pandey B, Yadav TP. Microstructure, pathophysiology, and potential therapeutics of COVID-19: A comprehensive review. J Med Virol. 2021;93(1):275-99.
12. Hasan SS, Capstick T, Ahmed R, Kow CS, Mazhar F, Merchant HA, et al. Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. Expert Rev Respir Med. 2020;14(11):1149-63.
13. Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J Mol Histol. 2020;51(6):613-28.
14. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol. 2020;214(12):108393.
15. Kelleni MT. Early use of non-steroidal anti-inflammatory drugs in COVID-19 might reverse pathogenesis, prevent complications and improve clinical outcomes. Biomed Pharmacother. 2021;133(6):110982.
16. Mirshafiey A, Taeb M, Mortazavi-Jahromi SS, Jafarnezhad-Ansariha F, Rehm BHA, Esposito E, et al. Introduction of β-d-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property based on COX-1/COX-2 activity and gene expression. Pharmacol Rep. 2017;69(5):1067-72.
17. Jafarnezhad-Ansariha F, Yekaninejad MS, Jamshidi AR, Mansouri R, Vojdanian M, Mahmoudi M, et al. The effects of β-D-mannuronic acid (M2000), as a novel NSAID, on COX1 and COX2 activities and gene expression in ankylosing spondylitis patients and the murine monocyte/macrophage, J774 cell line. Inflammopharmacology. 2018;26(2):375-84.
18. Fattahi MJ, Abdollahi M, Agha Mohammadi A, Rastkari N, Khorasani R, Ahmadi H, et al. Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug. Immunopharmacol Immunotoxicol. 2015;37(6):535-40.
19. Mortazavi-Jahromi SS, Jamshidi MM, Farazmand A, Aghazadeh Z, Yousefi M, Mirshafiey A. Pharmacological effects of β-D-mannuronic acid (M2000) on miR-146a, IRAK1, TRAF6 and NF-κB gene expression, as target molecules in inflammatory reactions. Pharmacol Rep. 2017;69(3):479-84.
20. Fard NA, Tabrizian N, Mirzaei R, Motamed N, Zavareh FT, Mirshafiey A. The Safety Property of β-D-Mannuronic Acid (M2000) as a Novel Immunosuppressive Agent on Differentiation, Maturation and Function of Human Dendritic Cells. Curr Drug Discov Technol. 2016;13(3):164-9.
21. Aletaha S, Haddad L, Roozbehkia M, Bigdeli R, Asgary V, Mahmoudi M, et al. M2000 (β-D-Mannuronic Acid) as a Novel Antagonist for Blocking the TLR2 and TLR4 Downstream Signalling Pathway. Scand J Immunol. 2017;85(2):122-9.
22. Aslani M, Ahmadzadeh A, Aghazadeh Z, Zaki-Dizaji M, Sharifi L, Hosseini M, et al. Influence of β-D-mannuronic Acid, as a New Member of Non-steroidal Anti- Inflammatory Drugs Family, on the Expression Pattern of Chemokines and their Receptors in Rheumatoid Arthritis. Curr Drug Discov Technol. 2021;18(1):65-74.
23. Fanelli V, Vlachou A, Ghannadian S, Simonetti U, Slutsky AS, Zhang H. Acute respiratory distress syndrome: new definition, current and future therapeutic options. J Thorac Dis. 2013;5(3):326-34.
24. Fuss IJ, Kanof ME, Smith PD, Zola H. Isolation of whole mononuclear cells from peripheral blood and cord blood. Curr Protoc Immunol. 2009;Chapter 7:Unit7.1.
25. Valizadeh H, Abdolmohammadi-Vahid S, Danshina S, Ziya Gencer M, Ammari A, Sadeghi A, et al. Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients. Int Immunopharmacol. 2020;89(Pt B):107088.
26. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
27. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74.
28. Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. 2022;23(1):3-20.
29. Darif D, Hammi I, Kihel A, El Idrissi Saik I, Guessous F, Akarid K. The proinflammatory cytokines in COVID-19 pathogenesis: What goes wrong? Microb Pathog. 2021;153:104799-.
30. Fara A, Mitrev Z, Rosalia RA, Assas BM. Cytokine storm and COVID-19: a chronicle of proinflammatory cytokines. Open Biol. 2020;10(9):200160.
31. Hussman JP. Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention. Front Pharmacol. 2020;11:1169.
32. Yang L, Xie X, Tu Z, Fu J, Xu D, Zhou Y. The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduct Target Ther. 2021;6(1):255.
33. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev. 2020;7(6):998-1002.
34. Mantovani S, Daga S, Fallerini C, Baldassarri M, Benetti E, Picchiotti N, et al. Rare variants in Toll-like receptor 7 results in functional impairment and downregulation of cytokine-mediated signaling in COVID-19 patients. Genes Immun. 2022;23(1):51-6.
35. Li W, Qiao J, You Q, Zong S, Peng Q, Liu Y, et al. SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS. Front immunol. 2021;12.
36. de Queiroz TM, Lakkappa N, Lazartigues E. ADAM17-Mediated Shedding of Inflammatory Cytokines in Hypertension. Front Pharmacol. 2020;11:1154.
37. Aslani M, Mortazavi-Jahromi SS, Mirshafiey A. Cytokine storm in the pathophysiology of COVID-19: Possible functional disturbances of miRNAs. Int Immunopharmacol. 2021;101(Pt A):108172.
38. Johnson DE, O'Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018;15(4):234-48.
39. Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021;33(3):127-48.
40. Puccetti M, Costantini C, Ricci M, Giovagnoli S. Tackling Immune Pathogenesis of COVID-19 through Molecular Pharmaceutics. Pharmaceutics. 2021;13(4).
41. Kragholm K, Torp-Pedersen C, Fosbol E. Non-steroidal anti-inflammatory drug use in COVID-19. Lancet Rheumatol. 2021;3(7):e465-e6.
42. Zhou Q, Zhao S, Gan L, Wang Z, Peng S, Li Q, et al. Use of non-steroidal anti-inflammatory drugs and adverse outcomes during the COVID-19 pandemic: A systematic review and meta-analysis. EClinicalMedicine. 2022;46:101373.
43. Reese JT, Coleman B, Chan L, Blau H, Callahan TJ, Cappelletti L, et al. NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study. J Virol. 2022;19(1):84.
44. Seifirad S. Pirfenidone: A novel hypothetical treatment for COVID-19. Med Hypotheses. 2020;144:110005.
45. Rogero MM, Leão MC, Santana TM, Pimentel M, Carlini GCG, da Silveira TFF, et al. Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19. Free Radic Biol Med. 2020;156:190-9.
46. Wang R. Etoricoxib may inhibit cytokine storm to treat COVID-19. Med Hypotheses. 2021;150(14):110557.
47. Rehan M, Ahmed F, Howladar SM, Refai MY, Baeissa HM, Zughaibi TA, et al. A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm. Front Immunol. 2021;12:648250.
48. Bahbah EI, Negida A, Nabet MS. Purposing Saikosaponins for the treatment of COVID-19. Med Hypotheses. 2020;140:109782.
49. Raciti L, De Luca R, Raciti G, Arcadi FA, Calabrò RS. The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study. Med Sci (Basel). 2022;10(3).
50. Marinella MA. Indomethacin and resveratrol as potential treatment adjuncts for SARS-CoV-2/COVID-19. Int J Clin Pract. 2020;74(9):e13535.
51. Mirshafiey A, Cuzzocrea S, Rehm BH, Matsuo H. M2000: a revolution in pharmacology. Med Sci Monit. 2005;11(8):Pi53-63.
52. M MF, Motevaseli E, Maghsood F, Heidari-Kharaji M, Mirshafiey A. Anti-inflammatory Property of β-D-Mannuronic Acid (M2000) on Expression and Activity of Matrix Metalloproteinase-2 and -9 through CD147 Molecule in Phorbol Myristate Acetate-differentiated THP-1 Cells. Iran J Allergy Asthma Immunol. 2017;16(5):443-51.
53. Ahmadi H, Jamshidi AR, Mahmoudi M, Cuzzocrea S, Fattahi MJ, Barati A, et al. The Potent Inhibitory Effect of β-D-Mannuronic Acid (M2000) as a Novel NSAID with Immunosuppressive Property on Anti-Cyclic Citrullinated Peptide Antibodies, Rheumatoid Factor and Anti-dsDNA Antibodies in Patients with Rheumatoid Arthritis. Curr Drug Discov Technol. 2017;14(3):206-14.
54. Ahmadi H, Jamshidi AR, Gharibdoost F, Mahmoudi M, Rastkari N, Mostafaei S, et al. A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of β-D-mannuronic acid in rheumatoid arthritis patients. Inflammopharmacology. 2018;26(3):737-45.
55. Rezaieyazdi Z, Farooqi A, Soleymani-Salehabadi H, Ahmadzadeh A, Aslani M, Omidian S, et al. International multicenter randomized, placebo-controlled phase III clinical trial of β-D-mannuronic acid in rheumatoid arthritis patients. Inflammopharmacology. 2019;27(5):911-21.
56. Ahmadi H, Mahmoudi M, Gharibdoost F, Vojdanian M, Jamshidi AR, Fattahi MJ, et al. Targeting of circulating Th17 cells by β-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis. Inflammopharmacology. 2018;26(1):57-65.
57. Gaafar NAG, Aslani M, Aghazadeh Z, Razavi A, Mirshafiey A. The Oral Administration Effect of Drug Mannuronic Acid (M2000) on Gene Expression of Matrix and Tissue Inhibitor of Metalloproteinases in Rheumatoid Arthritis Patients. Curr Drug Discov Technol. 2020;17(5):704-10.
58. Gaafar NAG, Aslani M, Aghazadeh Z, Mortazavi-Jahromi SS, Razavi A, Mirshafiey A. Effects of mannuronic acid (M2000) on gene expression profile of signal transducer and activator of transcription proteins (STATs) in rheumatoid arthritis patients. Reumatismo. 2020;72(2):93-102.
59. Mortazavi-Jahromi SS, Ahmadzadeh A, Rezaieyazdi Z, Aslani M, Omidian S, Mirshafiey A. The role of β-d-mannuronic acid, as a new non-steroidal anti-inflammatory drug on expression of miR-146a, IRAK1, TRAF6, NF-κB and proinflammatory cytokines following a clinical trial in rheumatoid arthritis patients. Immunopharmacol Immunotoxicol. 2020;42(3):228-36.
60. del Valle-Mendoza J, Tarazona-Castro Y, Merino-Luna A, Carrillo-Ng H, Kym S, Aguilar-Luis MA, et al. Comparison of cytokines levels among COVID-19 patients living at sea level and high altitude. BMC Infect Dis. 2022;22(1):96.
| Files | ||
| Issue | Vol 21 No 6 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i6.11528 | |
| Keywords | ||
| Coronavirus disease of 2019 Mannuronic acid Severe acute respiratory syndrome coronavirus 2 | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Robat-Jazi B, Ghorban K, Gholami M, Samizadeh E, Aghazadeh Z, Shahrbaf MA, Dadmanesh M, Hosseini Rouzbahani N, Mirshafiey A. β-D-mannuronic Acid (M2000) and Inflammatory Cytokines in COVID-19; An In vitro Study. Iran J Allergy Asthma Immunol. 2022;21(6):677-686.
