Purinergic receptor ligands: the cytokine storm attenuators, potential therapeutic agents for the treatment of COVID-19

References

• Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl Med. 2020;382(8):727–733.
   PubMed Web of Science ®Google Scholar
• Dong X, Cao Y, Lu X, et al. Eleven faces of coronavirus disease 2019. Allergy. 2020;75(7):1699–1709.
   PubMed Web of Science ®Google Scholar
• Rodríguez Y, Novelli L, Rojas M, et al. Autoinflammatory and autoimmune conditions at the crossroad of COVID-19. J Autoimmun. 2020;114:102506.
   PubMed Web of Science ®Google Scholar
• Fara A, Mitrev Z, Rosalia RA, et al. Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines. Open Biol. 2020;10(9):200160.
   PubMed Web of Science ®Google Scholar
• Mangalmurti N, Hunter CA. Cytokine storms: understanding COVID-19. Immunity. 2020;53(1):19–25.
   PubMed Web of Science ®Google Scholar
• Mahmudpour M, Roozbeh J, Keshavarz M, et al. COVID-19 cytokine storm: the anger of inflammation. Cytokine. 2020;133:155151.
   PubMed Web of Science ®Google Scholar
• Behrens EM, Koretzky GA. Review: cytokine storm syndrome: looking toward the precision medicine era. Arthritis Rheumatol. 2017;69(6):1135–1143.
   PubMed Web of Science ®Google Scholar
• Du SQ, Yuan W. Mathematical modeling of interaction between innate and adaptive immune responses in COVID-19 and implications for viral pathogenesis. J Med Virol. 2020;92(9):1615–1628.
   PubMed Web of Science ®Google Scholar
• Tay MZ, Poh CM, Rénia L, et al. The Trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363–374.
   PubMed Web of Science ®Google Scholar
• Sethuraman N, Jeremiah SS, Ryo A. Interpreting diagnostic tests for SARS-CoV-2. JAMA. 2020;323(22):2249–2251.
   PubMed Web of Science ®Google Scholar
• Dinarello CA. Interleukin-18 and the pathogenesis of inflammatory diseases. Semin Nephrol. 2007;27(1):98–114.
   PubMed Web of Science ®Google Scholar
• Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2002;20(5 Suppl 27):S1–S13.
   PubMed Web of Science ®Google Scholar
• Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8(8):959–970.
   PubMed Web of Science ®Google Scholar
• Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117(20):10970–10975.
   PubMed Web of Science ®Google Scholar
• Mehta P, McAuley DF, Brown M, HLH Across Specialty Collaboration, UK, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–1034.
   PubMed Web of Science ®Google Scholar
• Stasi C, Fallani S, Voller F, et al. Treatment for COVID-19: an overview. Eur J Pharmacol. 2020;889:173644.
   PubMed Web of Science ®Google Scholar
• Liu P, Chen W, Chen J-P. Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manis javanica). Viruses. 2019;11(11):979.
   PubMed Web of Science ®Google Scholar
• Dos Anjos F, Simões JLB, Assmann CE, et al. Potential therapeutic role of purinergic receptors in cardiovascular disease mediated by SARS-CoV-2. J Immunol Res. 2020;2020:8632048.
   PubMed Web of Science ®Google Scholar
• Burnstock G. Purinergic signalling: from discovery to current developments. Exp Physiol. 2014;99(1):16–34.
   PubMed Web of Science ®Google Scholar
• Abbracchio MP, Burnstock G. Purinergic signalling: pathophysiological roles. Jpn J Pharmacol. 1998;78(2):113–145.
   PubMedGoogle Scholar
• Arulkumaran N, Unwin RJ, Tam FWK. A potential therapeutic role for P2X7 receptor (P2X7R) antagonists in the treatment of inflammatory diseases. Expert Opin Investig Drugs. 2011;20(7):897–915.
   PubMed Web of Science ®Google Scholar
• Iba T, Levy JH, Levi M, et al. Coagulopathy of coronavirus disease 2019. Crit Care Med. 2020;48(9):1358–1364.
   PubMed Web of Science ®Google Scholar
• Burnstock G. P2X ion channel receptors and inflammation. Purinergic Signal. 2016;12(1):59–67.
   PubMed Web of Science ®Google Scholar
• Di Virgilio F. P2X receptors and inflammation. Curr Med Chem. 2015;22(7):866–877.
   PubMed Web of Science ®Google Scholar
• Surprenant A, North RA. Signaling at purinergic P2X receptors. Annu Rev Physiol. 2009;71:333–359.
   PubMed Web of Science ®Google Scholar
• Haskó G, Kuhel DG, Chen J-F, et al. Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J. 2000;14(13):2065–2074.
   PubMed Web of Science ®Google Scholar
• Hasko G, Szabó C, Németh ZH, et al. Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice. J Immunol. 1996;157(10):4634–4640.
   PubMed Web of Science ®Google Scholar
• Csóka B, Németh ZH, Virág L, et al. A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli. Blood. 2007;110(7):2685–2695.
   PubMed Web of Science ®Google Scholar
• Csóka B, Himer L, Selmeczy Z, et al. Adenosine A2A receptor activation inhibits T helper 1 and T helper 2 cell development and effector function. FASEB J. 2008;22(10):3491–3499.
   PubMed Web of Science ®Google Scholar
• Sitkovsky MV. Use of the A2A adenosine receptor as a physiological immunosuppressor and to engineer inflammation in vivo. Biochem Pharmacol. 2003;65(4):493–501.
   PubMed Web of Science ®Google Scholar
• Kitakaze M, Minamino T, Node K, et al. Adenosine and cardioprotection in the diseased heart. Jpn Circ J. 1999;63(4):231–243.
   PubMedGoogle Scholar
• Lee JE, Bokoch G, Liang BT. A novel cardioprotective role of RhoA: new signaling mechanism for adenosine. FASEB J. 2001;15(11):1886–1894.
   PubMed Web of Science ®Google Scholar
• Liang BT, Jacobson KA. A physiological role of the adenosine A3 receptor: sustained cardioprotection. Proc Natl Acad Sci U S A. 1998;95(12):6995–6999.
   PubMed Web of Science ®Google Scholar
• Dougherty C, Barucha J, Schofield PR, et al. Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor. FASEB J. 1998;12(15):1785–1792.
   PubMed Web of Science ®Google Scholar
• Longhi MS, Moss A, Jiang ZG, et al. Purinergic signaling during intestinal inflammation. J Mol Med (Berl). 2017;95(9):915–925.
   PubMed Web of Science ®Google Scholar
• Haskó G, Csóka B, Németh ZH, et al. A(2B) adenosine receptors in immunity and inflammation. Trends Immunol. 2009;30(6):263–270.
   PubMed Web of Science ®Google Scholar
• Milne GR, Palmer TM. Anti-inflammatory and immunosuppressive effects of the A2A adenosine receptor. Sci World J. 2011;11:320–339.
   Web of Science ®Google Scholar
• Guerrero A. A2A adenosine receptor agonists and their potential therapeutic applications. An update. Curr Med Chem. 2018;25(30):3597–3612.
   PubMed Web of Science ®Google Scholar
• Németh ZH, Lutz CS, Csóka B, et al. Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol. 2005;175(12):8260–8270.
   PubMed Web of Science ®Google Scholar
• Csóka B, Németh ZH, Rosenberger P, et al. A2B adenosine receptors protect against sepsis-induced mortality by dampening excessive inflammation. J Immunol. 2010;185(1):542–550.
   PubMed Web of Science ®Google Scholar
• Csóka B, Selmeczy Z, Koscsó B, et al. Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J. 2012;26(1):376–386.
   PubMed Web of Science ®Google Scholar
• Koscsó B, Csóka B, Selmeczy Z, et al. Adenosine augments IL-10 production by microglial cells through an A2B adenosine receptor-mediated process. J Immunol. 2012;188(1):445–453.
   PubMed Web of Science ®Google Scholar
• Csóka B, Koscsó B, Töro G, et al. A2B adenosine receptors prevent insulin resistance by inhibiting adipose tissue inflammation via maintaining alternative macrophage activation. Diabetes. 2014;63(3):850–866.
   PubMed Web of Science ®Google Scholar
• Koscsó B, Csóka B, Kókai E, et al. Adenosine augments IL-10-induced STAT3 signaling in M2c macrophages. J Leukoc Biol. 2013;94(6):1309–1315.
   PubMed Web of Science ®Google Scholar
• Polosa R, Holgate ST. Adenosine receptors as promising therapeutic targets for drug development in chronic airway inflammation. Curr Drug Targets. 2006;7(6):699–706.
   PubMed Web of Science ®Google Scholar
• Zhong H, Belardinelli L, Maa T, et al. A(2B) adenosine receptors increase cytokine release by bronchial smooth muscle cells. Am J Respir Cell Mol Biol. 2004;30(1):118–125.
   PubMed Web of Science ®Google Scholar
• Zhong H, Belardinelli L, Maa T, et al. Synergy between A2B adenosine receptors and hypoxia in activating human lung fibroblasts. Am J Respir Cell Mol Biol. 2005;32(1):2–8.
   PubMed Web of Science ®Google Scholar
• Zhong H, Wu Y, Belardinelli L, et al. A2B adenosine receptors induce IL-19 from bronchial epithelial cells, resulting in TNF-alpha increase. Am J Respir Cell Mol Biol. 2006;35(5):587–592.
   PubMed Web of Science ®Google Scholar
• Feoktistov I, Biaggioni I. Role of adenosine A(2B) receptors in inflammation. Adv Pharmacol. 2011;61:115–144.
   PubMedGoogle Scholar
• Vivas D, Roldán V, Esteve-Pastor MA, et al. Recommendations on antithrombotic treatment during the COVID-19 pandemic. Position statement of the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology. Rev Esp Cardiol. 2020; 73:749–757.
   Web of Science ®Google Scholar
• Mabley J, Soriano F, Pacher P, et al. The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide, is protective in two murine models of colitis. Eur J Pharmacol. 2003;466(3):323–329.
   PubMed Web of Science ®Google Scholar
• Haskó G, Németh ZH, Vizi ES, et al. An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-gamma production and prevents lethality in endotoxemic mice. Eur J Pharmacol. 1998;358(3):261–268.
   PubMed Web of Science ®Google Scholar
• Szabó C, Scott GS, Virág L, et al. Suppression of macrophage inflammatory protein (MIP)-1alpha production and collagen-induced arthritis by adenosine receptor agonists. Br J Pharmacol. 1998;125(2):379–387.
   PubMed Web of Science ®Google Scholar
• Ohta A, Gorelik E, Prasad SJ, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A. 2006;103(35):13132–13137.
   PubMed Web of Science ®Google Scholar
• Németh ZH, Csóka B, Wilmanski J, et al. Adenosine A2A receptor inactivation increases survival in polymicrobial sepsis. J Immunol. 2006;176(9):5616–5626.
   PubMed Web of Science ®Google Scholar
• Tsuda M, Tozaki-Saitoh H, Inoue K. Pain and purinergic signaling. Brain Res Rev. 2010;63(1–2):222–232.
   PubMedGoogle Scholar
• Ruiz-Rodríguez VM, Cortes-García JD, de Jesús Briones-Espinoza M, et al. P2X4 receptor as a modulator in the function of P2X receptor in CD4+ T cells from peripheral blood and adipose tissue. Mol Immunol. 2019;112:369–377.
   PubMed Web of Science ®Google Scholar
• Bo X, Kim M, Nori SL, et al. Tissue distribution of P2X4 receptors studied with an ectodomain antibody. Cell Tissue Res. 2003;313(2):159–165.
   PubMed Web of Science ®Google Scholar
• Turner CM, Vonend O, Chan C, et al. The pattern of distribution of selected ATP-sensitive P2 receptor subtypes in normal rat kidney: an immunohistological study. Cells Tissues Organs. 2003;175(2):105–117.
   PubMed Web of Science ®Google Scholar
• Antonioli L, Blandizzi C, Fornai M, et al. P2X4 receptors, immunity, and sepsis. Curr Opin Pharmacol. 2019;47:65–74.
   PubMed Web of Science ®Google Scholar
• Csóka B, Németh ZH, Szabó I, et al. Macrophage P2X4 receptors augment bacterial killing and protect against sepsis. JCI Insight. 2018;3(11):e99431.
   PubMed Web of Science ®Google Scholar
• Ferrari D, Pizzirani C, Adinolfi E, et al. The P2X 7 receptor: a key player in IL-1 processing and release. J Immunol. 2007;179(12):8569.3–8569.
   Web of Science ®Google Scholar
• Chen Q, Wu H, Qin S, et al. The P2X7 receptor involved in gp120-induced cell injury in BV2 microglia. Inflammation. 2016;39(5):1814–1826.
   PubMed Web of Science ®Google Scholar
• Wang H, Hong L-J, Huang J-Y, et al. P2RX7 sensitizes Mac-1/ICAM-1-dependent leukocyte-endothelial adhesion and promotes neurovascular injury during septic encephalopathy. Cell Res. 2015;25(6):674–690.
   PubMed Web of Science ®Google Scholar
• Mecha M, Feliú A, Iñigo PM, et al. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors. Neurobiol Dis. 2013;59:141–150.
   PubMed Web of Science ®Google Scholar
• Tewari M, Varghese RK, Menon M, et al. Astrocytes mediate HIV‐1 tat‐induced neuronal damage via ligand‐gated ion channel P2X7R. J Neurochem. 2015; 132:464–476.
   PubMed Web of Science ®Google Scholar
• Zhou F, Liu X, Gao L, et al. HIV-1 Tat enhances purinergic P2Y4 receptor signaling to mediate inflammatory cytokine production and neuronal damage via PI3K/Akt and ERK MAPK pathways. J Neuroinflammation. 2019;16(1):71.
   PubMedGoogle Scholar
• Pingle SC, Jajoo S, Mukherjea D, et al. Activation of the adenosine A1 receptor inhibits HIV-1 tat-induced apoptosis by reducing nuclear factor-kappaB activation and inducible nitric-oxide synthase. Mol Pharmacol. 2007;72(4):856–867.
   PubMed Web of Science ®Google Scholar
• Guerra AN, Fisette PL, Pfeiffer ZA, et al. Purinergic receptor regulation of LPS-induced signaling and pathophysiology. J Endotoxin Res. 2003;9(4):256–263.
   PubMedGoogle Scholar
• Lopes RD, Heizer G, Aronson R, et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med. 2019;380(16):1509–1524.
   PubMed Web of Science ®Google Scholar
• Wang D, Yang X-H, Zhang J-D, et al. Compared efficacy of clopidogrel and ticagrelor in treating acute coronary syndrome: a meta-analysis. BMC Cardiovasc Disord. 2018;18:1–7.
   PubMed Web of Science ®Google Scholar
• Lazarowski ER, Boucher RC. UTP as an extracellular signaling molecule. News Physiol Sci. 2001;16:1–5.
   PubMedGoogle Scholar
• Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18–22.
   PubMed Web of Science ®Google Scholar
• Mao L, Wang M, Chen S, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan. China: a retrospective case series study. JAMA Neurol. 2020;77(6):683–690.
   PubMed Web of Science ®Google Scholar
• Jin Y, Yang H, Ji W, et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses. 2020;12(4):372.
   PubMed Web of Science ®Google Scholar
• Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med. 2020; 8(6):e46–e47.
   PubMed Web of Science ®Google Scholar
• Cicko S, Köhler TC, Ayata CK, et al. Extracellular ATP is a danger signal activating P2X7 receptor in a LPS mediated inflammation (ARDS/ALI). Oncotarget. 2018;9(55):30635–30648.
   PubMedGoogle Scholar
• Monção-Ribeiro LC, Cagido VR, Lima-Murad G, et al. Lipopolysaccharide-induced lung injury: role of P2X7 receptor. Respir Physiol Neurobiol. 2011;179(2–3):314–325.
   PubMed Web of Science ®Google Scholar
• Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1–23.
   PubMedGoogle Scholar
• Di Virgilio F, Tang Y, Sarti AC, et al. A rationale for targeting the P2X7 receptor in coronavirus disease 19. Br J Pharmacol. 2020;177(21):4990–4994.
   PubMed Web of Science ®Google Scholar
• Li G, He X, Zhang L, et al. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J Autoimmun. 2020;112:102463.
   PubMed Web of Science ®Google Scholar
• Geiger JD, Khan N, Murugan M, et al. Possible role of adenosine in COVID-19 pathogenesis and therapeutic opportunities. Front Pharmacol. 2020;11:594487.
   PubMed Web of Science ®Google Scholar
• Salvatore CA, Jacobson MA, Taylor HE, et al. Molecular cloning and characterization of the human A3 adenosine receptor. Proc Natl Acad Sci U S A. 1993;90(21):10365–10369.
   PubMed Web of Science ®Google Scholar
• Chunn JL, Young HWJ, Banerjee SK, et al. Adenosine-dependent airway inflammation and hyperresponsiveness in partially adenosine deaminase-deficient mice. J Immunol. 2001;167(8):4676–4685.
   PubMed Web of Science ®Google Scholar
• Blackburn MR, Lee CG, Young HWJ, et al. Adenosine mediates IL-13–induced inflammation and remodeling in the lung and interacts in an IL-13–adenosine amplification pathway. J Clin Invest. 2003;112(3):332–344.
   PubMed Web of Science ®Google Scholar
• Sharma AK, Linden J, Kron IL, et al. Protection from pulmonary ischemia-reperfusion injury by adenosine A2A receptor activation. Respir Res.  2009;10:1–9.
   PubMed Web of Science ®Google Scholar
• Gonzales JN, Gorshkov B, Varn MN, et al. Protective effect of adenosine receptors against lipopolysaccharide-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2014;306(6):L497–L507.
   PubMed Web of Science ®Google Scholar
• Falcone C, Caracciolo M, Correale P, et al. Can adenosine fight COVID-19 acute respiratory distress syndrome? JCM. 2020;9(9):3045.
   Google Scholar
• Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
   PubMed Web of Science ®Google Scholar
• Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
   PubMed Web of Science ®Google Scholar
• Monji F, Siddiquee AA-M, Hashemian F. Can pentoxifylline and similar xanthine derivatives find a niche in COVID-19 therapeutic strategies? A ray of hope in the midst of the pandemic. Eur J Pharmacol. 2020;887:173561.
   PubMed Web of Science ®Google Scholar
• Haskó G, Cronstein B. Methylxanthines and inflammatory cells. Handb Exp Pharmacol. 2011;200:457–468.
   Google Scholar
• Tilley SL. Methylxanthines in asthma. Handb Exp Pharmacol. 2011;200:439–456.
   Google Scholar
• Fredholm BB, Irenius E, Kull B, et al. Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells. Biochem Pharmacol. 2001;61(4):443–448.
   PubMed Web of Science ®Google Scholar
• Fredholm BB, Bättig K, Holmén J, et al. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999;51(1):83–133.
   PubMed Web of Science ®Google Scholar
• Yegutkin GG. Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta. 2008;1783(5):673–694.
   PubMed Web of Science ®Google Scholar
• Mustafa SJ, Nadeem A, Fan M, et al. Effect of a specific and selective A(2B) adenosine receptor antagonist on adenosine agonist AMP and allergen-induced airway responsiveness and cellular influx in a mouse model of asthma. J Pharmacol Exp Ther. 2007;320(3):1246–1251.
   PubMed Web of Science ®Google Scholar
• Meiners I, Hauschildt S, Nieber K, et al. Pentoxyphylline and propentophylline are inhibitors of TNF-alpha release in monocytes activated by advanced glycation endproducts. J Neural Transm (Vienna). 2004;111(3):441–447.
   PubMed Web of Science ®Google Scholar
• Pouya FD, Nemati M, Asl ER, et al. The combination effects of theophylline and corticosteroids in COVID-19. Health Biotechnol Biopharma. 2020;4(3):1–5.
   Google Scholar
• Liu Y, Zhou LJ, Wang J, et al. TNF-α differentially regulates synaptic plasticity in the hippocampus and spinal cord by microglia-dependent mechanisms after peripheral nerve injury. J Neurosci. 2017;37(4):871–881.
   PubMed Web of Science ®Google Scholar
• Link AA, Kino T, Worth JA, et al. Ligand-activation of the adenosine A2a receptors inhibits IL-12 production by human monocytes. J Immunol. 2000;164(1):436–442.
   PubMed Web of Science ®Google Scholar
• González-Espinoza L, Rojas-Campos E, Medina-Pérez M, et al. Pentoxifylline decreases serum levels of tumor necrosis factor alpha, interleukin 6 and C-reactive protein in hemodialysis patients: results of a randomized double-blind, controlled clinical trial. Nephrol Dial Transplant. 2012;27(5):2023–2028.
   PubMed Web of Science ®Google Scholar
• Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71(15):762–768.
   PubMed Web of Science ®Google Scholar
• Conti P, Ronconi G, Caraffa AL, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020; 34:1.
   PubMed Web of Science ®Google Scholar
• DiNicolantonio JJ, Barroso-Aranda J. Harnessing adenosine A2A receptors as a strategy for suppressing the lung inflammation and thrombotic complications of COVID-19: Potential of pentoxifylline and dipyridamole. Med Hypotheses. 2020;143:110051.
   Google Scholar
• Di Virgilio F, Vuerich M. Purinergic signaling in the immune system. Auton Neurosci. 2015;191:117–123.
   PubMed Web of Science ®Google Scholar
• Johnston-Cox HA, Yang D, Ravid K. Physiological implications of adenosine receptor-mediated platelet aggregation. J Cell Physiol. 2011;226(1):46–51.
   PubMed Web of Science ®Google Scholar
• Macatangay BJC, Jackson EK, Abebe KZ, et al. A randomized, placebo-controlled, pilot clinical trial of dipyridamole to decrease human immunodeficiency virus-associated chronic inflammation. J Infect Dis. 2020;221(10):1598–1606.
   PubMed Web of Science ®Google Scholar
• Liu X, Li Z, Liu S, et al. Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. Acta Pharm Sin B. 2020;10(7):1205–1215.
   PubMed Web of Science ®Google Scholar
• Ben-Chetrit E, Bergmann S, Sood R. Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatology (Oxford). 2006;45(3):274–282.
   PubMed Web of Science ®Google Scholar
• Leung YY, Yao Hui LL, Kraus VB. Colchicine-Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. 2015;45(3):341–350.
   PubMed Web of Science ®Google Scholar
• Chia EW, Grainger R, Harper JL. Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis: a rationale for use of low-dose colchicine. Br J Pharmacol. 2008;153(6):1288–1295.
   PubMed Web of Science ®Google Scholar
• Li Z, Davis GS, Mohr C, et al. Inhibition of LPS-induced tumor necrosis factor-alpha production by colchicine and other microtubule disrupting drugs. Immunobiology. 1996;195(4–5):624–639.
   PubMed Web of Science ®Google Scholar
• Kiraz S, Ertenli I, Arici M, et al. Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Clin Exp Rheumatol. 1998;16:721–724.
   PubMed Web of Science ®Google Scholar
• Takenouchi T, Sugama S, Iwamaru Y, et al. Modulation of the ATP-induced release and processing of IL-1beta in microglial cells. Crit Rev Immunol. 2009;29(4):335–345.
   PubMed Web of Science ®Google Scholar
• Marques-Da-Silva C, Chaves MM, Castro NG, et al. Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: Implications for its therapeutic action. Br J Pharmacol. 2011;163(5):912–926.
   PubMed Web of Science ®Google Scholar
• Deftereos SG, Giannopoulos G, Vrachatis DA, GRECCO-19 Investigators, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial. JAMA Netw Open. 2020;3(6):e2013136.
   PubMed Web of Science ®Google Scholar
• Misawa T, Takahama M, Kozaki T, et al. Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat Immunol. 2013;14(5):454–460.
   PubMed Web of Science ®Google Scholar
• Robertson S, Martínez GJ, Payet CA, et al. Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation. *2016;130:1237–1246.
   Google Scholar
• Martínez GJ, Robertson S, Barraclough J, et al. Colchicine acutely suppresses local cardiac production of inflammatory cytokines in patients with an acute coronary syndrome. J Am Heart Assoc. 2015;4:e002128.
   PubMed Web of Science ®Google Scholar
• Chen IY, Moriyama M, Chang MF, et al. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol. 2019;10:50.
   PubMed Web of Science ®Google Scholar
• Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol. 2001;9(3):113–114.
   PubMed Web of Science ®Google Scholar
• Grailer JJ, Canning BA, Kalbitz M, et al. Critical role for the NLRP3 inflammasome during acute lung injury. J Immunol. 2014;192(12):5974–5983.
   PubMed Web of Science ®Google Scholar
• Li D, Ren W, Jiang Z, et al. Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury. Mol Med Rep. 2018;18:4399–4409.
   PubMed Web of Science ®Google Scholar
• Dolinay T, Kim YS, Howrylak J, et al. Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med. 2012;185(11):1225–1234.
   PubMed Web of Science ®Google Scholar
• Jones HD, Crother TR, Gonzalez-Villalobos RA, et al. The NLRP3 inflammasome is required for the development of hypoxemia in LPS/mechanical ventilation acute lung injury. Am J Respir Cell Mol Biol. 2014;50(2):270–280.
   PubMed Web of Science ®Google Scholar
• Papadopoulos C, Patoulias D, Teperikidis E, et al. Colchicine as a potential therapeutic agent against cardiovascular complications of COVID-19: an exploratory review. SN Compr Clin Med. 2020;2(9):1419–1429.
   Google Scholar
• Vrachatis DA, Giannopoulos GV, Giotaki SG, et al. Impact of colchicine on mortality in patients with COVID-19: a meta-analysis. Hellenic J Cardiol. 2021:S1109–S9666.
   Web of Science ®Google Scholar
• Piantoni S, Andreoli L, Colombo E, et al. Response to: “Correspondence on ‘Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome’” by Kawada. Ann Rheum Dis. 2021;79:1286–1289.
   Web of Science ®Google Scholar
• Della-Torre E, Della-Torre F, Kusanovic M, et al. Treating COVID-19 with colchicine in community healthcare setting. Clin Immunol. 2020;217:108490.
   PubMed Web of Science ®Google Scholar
• Yue Q, Liu T, Cheng Z. Protective effect of colchicine on LPS-Induced lung injury in rats via inhibition of P-38, ERK1/2, and JNK activation. Pharmacology. 2020;105(11–12):639–644.
   PubMed Web of Science ®Google Scholar
• Tynan RJ, Weidenhofer J, Hinwood M, et al. A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia. Brain Behav Immun. 2012;26(3):469–479.
   PubMed Web of Science ®Google Scholar
• Chen CY, Yeh YW, Kuo SC, et al. Differences in immunomodulatory properties between venlafaxine and paroxetine in patients with major depressive disorder. Psychoneuroendocrinology. 2018;87:108–118.
   PubMed Web of Science ®Google Scholar
• Jha MK, Trivedi MH. Personalized antidepressant selection and pathway to novel treatments: clinical utility of targeting inflammation. IJMS. 2018;19(1):233.
   Google Scholar
• Nagata K, Imai T, Yamashita T, et al. Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief. Mol Pain. 2009;5:20–8069.
   PubMed Web of Science ®Google Scholar
• Hempel C, Nörenberg W, Sobottka H, et al. The phenothiazine-class antipsychotic drugs prochlorperazine and trifluoperazine are potent allosteric modulators of the human P2X7 receptor. Neuropharmacology. 2013;75:365–379.
   PubMed Web of Science ®Google Scholar
• Dao-Ung P, Skarratt KK, Fuller SJ, et al. Paroxetine suppresses recombinant human P2X7 responses. Purinergic Signal. 2015;11(4):481–490.
   PubMed Web of Science ®Google Scholar
• Yamashita T, Yamamoto S, Zhang J, et al. Duloxetine inhibits microglial P2X4 receptor function and alleviates neuropathic pain after peripheral nerve injury. PLoS One. 2016;11(10):e0165189.
   PubMed Web of Science ®Google Scholar
• Kubera M, Simbirtsev A, Mathison R, et al. Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice. Psychiatry Res. 2000;96(3):255–266.
   PubMed Web of Science ®Google Scholar
• Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357–1366.
   PubMed Web of Science ®Google Scholar
• He JH, Liu RP, Peng YM, et al. Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation. J Neuroinflammation. 2021;18:1–14.
   PubMed Web of Science ®Google Scholar
• Kubera M, Roman A, Basta-Kaim A, et al. Effect of acute and repeated treatment with mirtazapine on the immunity of noradrenaline transporter knockout C57BL/6J mice. Pharmacol Biochem Behav. 2006;85(4):813–819.
   PubMed Web of Science ®Google Scholar
• Kabiri M, Hemmatpour A, Zare F, et al. Paroxetine modulates immune responses by activating a JAK2/STAT3 signaling pathway. J Biochem Mol Toxicol. 2020;34(5):e22464.
   PubMed Web of Science ®Google Scholar
• Zhe Q, Sulei W, Weiwei T, et al. Effects of Jiaotaiwan on depressive-like behavior in mice after lipopolysaccharide administration. Metab Brain Dis. 2017;32(2):415–426.
   PubMed Web of Science ®Google Scholar
• Köhler CA, Freitas TH, Stubbs B, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol. 2018;55:4195–4206.
   PubMed Web of Science ®Google Scholar
• Hojyo S, Uchida M, Tanaka K, et al. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020;40:1–7.
   PubMed Web of Science ®Google Scholar
• Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect. 2020;80(6):607–613.
   PubMed Web of Science ®Google Scholar
• Hoertel N, Sánchez-Rico M, Vernet R, et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study. Mol Psychiatry. 2021;1–14.
   Web of Science ®Google Scholar
• Gulbins E, Palmada M, Reichel M, et al. Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs. Nat Med. 2013;19(7):934–938.
   PubMed Web of Science ®Google Scholar
• Carpinteiro A, Edwards MJ, Hoffmann M, et al. Pharmacological inhibition of acid sphingomyelinase prevents uptake of SARS-CoV-2 by epithelial cells. Cell Rep Med. 2020;1(8):100142.
   PubMedGoogle Scholar
• Lenze EJ, Mattar C, Zorumski CF, et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial. JAMA. 2020;324(22):2292–2300.
   PubMed Web of Science ®Google Scholar
• Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020; :583: 1–13.
   Web of Science ®Google Scholar
• Zimniak M, Kirschner L, Hilpert H, et al. The serotonin reuptake inhibitor fluoxetine inhibits SARS-CoV-2 in human lung tissue. Sci Rep. 2021;11:5890.
   PubMed Web of Science ®Google Scholar
• Abdulqawi R, Dockry R, Holt K, et al. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015;385(9974):1198–1205.
   PubMed Web of Science ®Google Scholar
• Abu-Zaid A, Aljaili A, Althaqib A, et al. Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough: a systematic review and meta-analysis of randomized controlled trials. Ann Thorac Med. 2021;16(2):127–140.
   PubMed Web of Science ®Google Scholar
• Cattaneo M. The platelet P2 receptors. Platelets. Academic Press; 2019;35:259–277.
   Google Scholar
• Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev. 2007;87(2):659–797.
   PubMed Web of Science ®Google Scholar
• Shinoda M, Feng B, Gebhart GF. Peripheral and central P2X receptor contributions to colon mechanosensitivity and hypersensitivity in the mouse. Gastroenterology. 2009;137(6):2096–2104.
   PubMed Web of Science ®Google Scholar
• Teixeira JM, Oliveira MCG, Parada CA, et al. Peripheral mechanisms underlying the essential role of P2X7 receptors in the development of inflammatory hyperalgesia. Eur J Pharmacol. 2010;644(1–3):55–60.
   PubMed Web of Science ®Google Scholar
• Prado FC, Araldi D, Vieira AS, et al. Neuronal P2X3 receptor activation is essential to the hyperalgesia induced by prostaglandins and sympathomimetic amines released during inflammation. Neuropharmacology. 2013;67:252–258.
   PubMed Web of Science ®Google Scholar
• Tempest HV, Dixon AK, Turner WH, et al. P2X2 and P2X3 receptor expression in human bladder urothelium and changes in interstitial cystitis. BJU Int. 2004;93:1344–1348.
   PubMed Web of Science ®Google Scholar
• Ding S, Zhu L, Tian Y, et al. P2X3 receptor involvement in endometriosis pain via ERK signaling pathway. PLoS One. 2017;12(9):e0184647.
   PubMed Web of Science ®Google Scholar
• Teixeira JM, Bobinski F, Parada CA, et al. P2X3 and P2X2/3 receptors play a crucial role in articular hyperalgesia development through inflammatory mechanisms in the knee joint experimental synovitis. Mol Neurobiol. 2017;54(8):6174–6186.
   PubMed Web of Science ®Google Scholar
• Ford AP, Undem BJ. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders. Front Cell Neurosci. 2013;7:267.
   PubMed Web of Science ®Google Scholar
• Khakh BS, North RA. Alan North R. P2X receptors as cell-surface ATP sensors in health and disease. Nature. 2006;442(7102):527–532.
   PubMed Web of Science ®Google Scholar
• Smith JA, Kitt M, Sher M, et al. 2 Dose-escalation study with AF-219, a P2X3 antagonist for the treatment of chronic cough. D23. Symptoms matter cough, dyspnea, fatigue qual. Life.; American Thoracic Society. Am J Respiratory Critical Care Med. 2016;193:A6524–A6524.
   Web of Science ®Google Scholar
• Canning BJ, Chang AB, Bolser DC, et al. Anatomy and neurophysiology of cough: CHEST guideline and expert panel report. Chest. 2014;146:1633–1648.
   PubMed Web of Science ®Google Scholar
• De Maio A, Hightower LE. COVID-19, acute respiratory distress syndrome (ARDS), and hyperbaric oxygen therapy (HBOT): what is the link? Cell Stress Chaperones. 2020;25(5):717–720.
   PubMed Web of Science ®Google Scholar
• Grant MC, Geoghegan L, Arbyn M, et al. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): a systematic review and meta-analysis of 148 studies from 9 countries. PLoS One. 2020;15(6):e0234765.
   PubMed Web of Science ®Google Scholar
• Goërtz YMJ, Van Herck M, Delbressine JM, et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020; 6:00542–02020.
   PubMedGoogle Scholar
• Song WJ, Hui CKM, Hull JH, et al. Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses. Lancet Respir Med. 2021;9(5):533–544.
   PubMed Web of Science ®Google Scholar
• Ferri N, Corsini A, Bellosta S. Pharmacology of the new P2Y12 receptor inhibitors: insights on pharmacokinetic and pharmacodynamic properties. Drugs. 2013;73(15):1681–1709.
   PubMed Web of Science ®Google Scholar
• Baqi Y, Müller CE. Antithrombotic P2Y12 receptor antagonists: recent developments in drug discovery. Drug Discov Today. 2019;24(1):325–333.
   PubMed Web of Science ®Google Scholar
• McFadyen JD, Schaff M, Peter K. Current and future antiplatelet therapies: emphasis on preserving haemostasis. Nat Rev Cardiol. 2018;15(3):181–191.
   PubMed Web of Science ®Google Scholar
• Le Duc D, Schulz A, Lede V, et al. P2Y receptors in immune response and inflammation. Adv Immunol. 2017;136:85–121.
   PubMed Web of Science ®Google Scholar
• Mansour A, Bachelot-Loza C, Nesseler N, et al. P2Y12 inhibition beyond thrombosis: effects on inflammation. IJMS. 2020;21(4):1391.
   Google Scholar
• Haynes SE, Hollopeter G, Yang G, et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci. 2006;9(12):1512–1519.
   PubMed Web of Science ®Google Scholar
• Muniz VS, Baptista-dos-Reis R, Benjamim CF, et al. Purinergic P2Y12 receptor activation in eosinophils and the schistosomal host response. PLoS One. 2015;10(10):e0139805.
   PubMed Web of Science ®Google Scholar
• Kronlage M, Song J, Sorokin L, et al. Autocrine purinergic receptor signaling is essential for macrophage chemotaxis. Sci Signal. 2010;3(132):ra55.
   PubMed Web of Science ®Google Scholar
• Vemulapalli H, Albayati S, Patwa VC, et al. ADP exerts P2Y 12-dependent and P2Y 12-independent effects on primary human T cell responses to stimulation. J Cell Commun Signal. 2019;14:1–16.
   Web of Science ®Google Scholar
• Turner MD, Nedjai B, Hurst T, et al. Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta. 2014;1843(11):2563–2582.
   PubMed Web of Science ®Google Scholar
• Assinger A, Schrottmaier WC, Salzmann M, et al. Platelets in sepsis: an update on experimental models and clinical data. Front Immunol. 2019;10:1687.
   PubMed Web of Science ®Google Scholar
• Mathew P. Platelets in thrombotic and non-thrombotic disorders. J Pediatr Hematol Oncol. 2003;25(6):510.
   PubMedGoogle Scholar
• Liverani EE, Kilpatrick LY, Tsygankov A, et al. The role of P2Y12 receptor and activated platelets during inflammation. Curr Drug Targets. 2014;15(7):720–728.
   PubMed Web of Science ®Google Scholar
• Wang X, Deng H, Li T, et al. Clopidogrel reduces lipopolysaccharide-induced inflammation and neutrophil-platelet aggregates in an experimental endotoxemic model. J Biochem Mol Toxicol. 2019;33(4):e22279.
   PubMed Web of Science ®Google Scholar
• Sexton TR, Zhang G, Macaulay TE, et al. Ticagrelor reduces thromboinflammatory markers in patients with pneumonia. JACC Basic Transl Sci. 2018;3(4):435–449.
   PubMedGoogle Scholar
• Hagiwara S, Iwasaka H, Hasegawa A, et al. Adenosine diphosphate receptor antagonist clopidogrel sulfate attenuates LPS-induced systemic inflammation in a rat model. Shock. 2011;35(3):289–292.
   PubMed Web of Science ®Google Scholar
• Thomas MR, Outteridge SN, Ajjan RA, et al. Platelet P2Y12 inhibitors reduce systemic inflammation and its prothrombotic effects in an experimental human model. Arterioscler Thromb Vasc Biol. 2015;35(12):2562–2570.
   PubMed Web of Science ®Google Scholar
• Lussana F, Di Marco F, Terraneo S, et al. Effect of prasugrel in patients with asthma: results of PRINA, a randomized, double‐blind, placebo‐controlled, cross‐over study. J Thromb Haemost. 2015;13(1):136–141.
   PubMed Web of Science ®Google Scholar
• Tsai M-J, Ou S-M, Shih C-J, et al. Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study. Intensive Care Med. 2015;41(5):806–813.
   PubMed Web of Science ®Google Scholar
• Yuan G, Wahlqvist ML, He G, et al. Natural products and anti-inflammatory activity. J Clin Nutr. 2006;15:143–152.
   Google Scholar
• Pacheco PAF, Diogo RT, Magalhães BQ, et al. Plant natural products as source of new P2 receptors ligands. Fitoterapia. 2020;146:104709.
   PubMed Web of Science ®Google Scholar
• Adinolfi E, Giuliani AL, De Marchi E, et al. The P2X7 receptor: a main player in inflammation. Biochem Pharmacol. 2018;151:234–244.
   PubMed Web of Science ®Google Scholar
• Frutuoso V, da S, Monteiro MM, et al. Analgesic and anti-inflammatory activity of the aqueous extract of Rheedia longifolia planch & triana. Mem Inst Oswaldo Cruz. 2007;102(1):91–96.
   PubMed Web of Science ®Google Scholar
• Santos JAA, Fidalgo-Neto AA, Faria RX, et al. Effect of Rheedia longifolia leaf extract and fractions on the P2X7 receptor in vitro: novel antagonists? J Med Food. 2011;14(9):920–929.
   PubMed Web of Science ®Google Scholar
• Nuka E, Ohnishi K, Terao J, et al. ATP/P2X7 receptor signaling as a potential anti-inflammatory target of natural polyphenols. PLoS One. 2018;13(9):e0204229.
   PubMed Web of Science ®Google Scholar
• Li M, Shi A, Pang H, et al. Safety, tolerability, and pharmacokinetics of a single ascending dose of baicalein chewable tablets in healthy subjects. J Ethnopharmacol. 2014;156:210–215.
   PubMed Web of Science ®Google Scholar
• Berman AY, Motechin RA, Wiesenfeld MY, et al. The therapeutic potential of resveratrol: a review of clinical trials. Oncology. 2017;1:1–9.
   Web of Science ®Google Scholar
• Ramírez-Garza SL, Laveriano-Santos EP, Marhuenda-Muñoz M, et al. Health effects of resveratrol: results from human intervention trials. Nutrients. 2018;10(12):1892.
   Web of Science ®Google Scholar
• Tu Y, Gong C, Ding L, et al. A high concentration of fatty acids induces TNF-α as well as NO release mediated by the P2X4 receptor, and the protective effects of puerarin in RAW264.7 cells. Food Funct. 2017;8(12):4336–4346.
   PubMed Web of Science ®Google Scholar
• Zheng Q-H, Li X-L, Mei Z-G, et al. Efficacy and safety of puerarin injection in curing acute ischemic stroke: a meta-analysis of randomized controlled trials. Medicine. 2017;96:e5803.
   PubMed Web of Science ®Google Scholar
• Izhaki I. Emodin – a secondary metabolite with multiple ecological functions in higher plants. New Phytol. 2002;155(2):205–217.
   Web of Science ®Google Scholar
• Zhang Q, Hu F, Guo F, et al. Emodin attenuates adenosine triphosphate-induced pancreatic ductal cell injury in vitro via the inhibition of the P2X7/NLRP3 signaling pathway. Oncol Rep. 2019;42(4):1589–1597.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Tao X, Xia S, et al. Emodin attenuated severe acute pancreatitis via the P2X ligand-gated ion channel 7/NOD-like receptor protein 3 signaling pathway. Oncol Rep. 2019;41(1):270–278.
   PubMed Web of Science ®Google Scholar
• Zhou Y-X, Xia W, Yue W, et al. Rhein: a review of pharmacological activities. Evid Based Complement Alternat Med. 2015;2015:578107.
   PubMed Web of Science ®Google Scholar
• Hu F, Xing F, Zhu G, et al. Rhein antagonizes P2X 7 receptor in rat peritoneal macrophages. Sci Rep. 2015;5:1–15.
   Web of Science ®Google Scholar