Potential Regulation of NF‑κB by Curcumin in Coronavirus‑Induced Cytokine Storm and Lung Injury

Mina Gholami, Fatemeh Adibipour, Sanaz M. Valipour, Luis Ulloa, Majid Motaghinejad


The current pandemic coronavirus disease‑19 (COVID‑19) is still a global medical and economic emergency with over 244 million confirmed infections and over 4.95 million deaths by October 2021, in less than 2 years. Severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome coronavirus (MERS), and COVID‑19 are three recent coronavirus pandemics with major medical and economic implications. Currently, there is no effective treatment for these infections. One major pathological hallmark of these infections is the so‑called ‘cytokine storm,’ which depicts an unregulated production of inflammatory cytokines inducing detrimental inflammation leading to organ injury and multiple organ failure including severe pulmonary, cardiovascular, and kidney failure in COVID‑19. Several studies have suggested the potential of curcumin to inhibit the replication of some viruses similar to coronaviruses. Multiple experimental and clinical studies also reported the anti‑inflammatory potential of curcumin in multiple infectious and inflammatory disorders. Thus, we hypothesized that curcumin may provide antiviral and anti‑inflammatory effects for treating COVID‑19. Although these studies suggest that curcumin could serve as an adjuvant treatment for COVID‑19, its molecular mechanisms are still debated, especially its potential to modulate the toll‑like receptors/TIR‑domain‑containing adapter‑inducing interferon‑β/nuclear factor kappa‑light‑chain‑enhancer of activated B cells (TLR/TRIF/NF‑κB) pathway. The preliminary results showed that curcumin modulates the nuclear factor kappa‑light‑chain‑enhancer of activated B cells (NF‑κB) pathway, a common pathway controlling cytokine production in multiple infectious and inflammatory disorders. Here, we hypothesize and discuss whether curcumin treatment may provide antiviral and anti‑inflammatory clinical advantages for treating COVID‑19 by modulating the TLR/TRIF/NF‑κB pathway. We also review the current data on curcumin and discuss potential experimental and clinical studies that require defining its potential clinical implications in COVID‑19.


Coronaviruses; curcumin; cytokine storm; TLRs/TRIF/NF‑κB pathway

Full Text:



World Health Organization. Infection Prevention and Control

Guidance for Long‑term Care Facilities in the Context of

COVID‑19: Interim Guidance, 21 March 2020. World Health

Organization; 2020.

Rothan HA, Byrareddy SN. The epidemiology and pathogenesis

of coronavirus disease (COVID‑19) outbreak. J Autoimmun

:102433. doi: 10.1016/j.jaut. 2020.102433.

Satija N, Lal SK. The molecular biology of SARS coronavirus.

Ann N Y Acad Sci 2007;1102:26‑38.

Spencer K‑A, Dee M, Britton P, Hiscox JA. Role of

phosphorylation clusters in the biology of the coronavirus

infectious bronchitis virus nucleocapsid protein. Virology


Lai MM. Coronavirus: Organization, replication and expression

of genome. Ann Rev Microbiol 1990;44:303.

Prentice E, Denison MR. The Cell Biology of Coronavirus

Infection. The Nidoviruses. Springer Berlin/Heidelberg; 2001.

p. 609‑14.

de Wit E, Rasmussen AL, Falzarano D, Bushmaker T,

Feldmann F, Brining DL, et al. Middle East respiratory

syndrome coronavirus (MERS‑CoV) causes transient lower

respiratory tract infection in rhesus macaques. Proc Natl Acad

Sci 2013;110:16598‑603.

Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients

with coronavirus disease 2019 (COVID‑19). JAMA Cardiol


Xu L, Liu J, Lu M, Yang D, Zheng X. Liver injury during

highly pathogenic human coronavirus infections. Liver Int


Lau K‑K, Yu W‑C, Chu C‑M, Lau S‑T, Sheng B, Yuen K‑Y.

Possible central nervous system infection by SARS coronavirus.

Emerg Infect Dis 2004;10:342‑4.

Chu KH, Tsang WK, Tang CS, Lam MF, Lai FM, To KF, et al.

Acute renal impairment in coronavirus‑associated severe acute

respiratory syndrome. Kidney Int 2005;67:698‑705.

Zheng Y‑Y, Ma Y‑T, Zhang J‑Y, Xie X. COVID‑19 and the

cardiovascular system. Nat Rev Cardiol 2020;17:259‑60.

Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence

of comorbidities in the novel Wuhan coronavirus (COVID‑19)

infection: A systematic review and meta‑analysis. Int J Infect Dis

;10. doi: 10.1016/j.ijid. 2020.03.017

Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al.

Pathological findings of COVID‑19 associated with acute

respiratory distress syndrome. Lancet Respir Med 2020;8:420‑2.

Channappanavar R, Perlman S. Pathogenic human coronavirus

infections: Causes and consequences of cytokine storm and

immunopathology. Semin Immunopathol 2017;39:529‑39.

Huang KJ, Su IJ, Theron M, Wu YC, Lai SK, Liu CC, et al.

An interferon‐γ‐related cytokine storm in SARS patients. J Med

Virol 2005;75:185‑94.

Netea MG, van der Meer JW, van Deuren M, Kullberg BJ.

Proinflammatory cytokines and sepsis syndrome: Not enough, or

too much of a good thing? Trends Immunol 2003;24:254‑8.

Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M,

et al. Current concepts in the diagnosis and management of

cytokine release syndrome. Blood 2014;124:188‑95.

Shimabukuro‑Vornhagen A, Gödel P, Subklewe M, Stemmler HJ,

Schlößer HA, Schlaak M, et al. Cytokine release syndrome.

J Immunother Cancer 2018;6:56. doi: 10.1186/s40425‑0180343‑9.

Fitzgerald JC, Weiss SL, Maude SL, Barrett DM, Lacey SF,

Melenhorst JJ, et al. Cytokine release syndrome after chimeric

antigen receptor T cell therapy for acute lymphoblastic leukemia.

Crit Care Med 2017;45:e124‑31.

Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of

cytokine release syndrome associated with the CAR T cell

therapy tisagenlecleucel. J Hematol Oncol 2018;11:35. doi:


Park JH, Romero FA, Taur Y, Sadelain M, Brentjens RJ,

Hohl TM, et al. Cytokine release syndrome grade as a predictive

marker for infections in patients with relapsed or refractory

B‑cell acute lymphoblastic leukemia treated with chimeric

antigen receptor T cells. Clin Infect Dis 2018;67:533‑40.

Gauthier J, Turtle CJ. Insights into cytokine release syndrome

and neurotoxicity after CD19‑specific CAR‑T cell therapy. Curr

Res Transl Med 2018;66:50‑2.

Norelli M, Camisa B, Barbiera G, Falcone L, Purevdorj A,

Genua M, et al. Monocyte‑derived IL‑1 and IL‑6 are differentially

required for cytokine‑release syndrome and neurotoxicity due to

CAR T cells. Nat Med 2018;24:739‑48.

Maude SL, Barrett D, Teachey DT, Grupp SA. Managing

cytokine release syndrome associated with novel T cell‑engaging

therapies. Cancer J 2014;20:119‑22.

Teachey DT, Lacey SF, Shaw PA, Melenhorst JJ, Maude SL,

Frey N, et al. Identification of predictive biomarkers for cytokine

release syndrome after chimeric antigen receptor T‑cell therapy

for acute lymphoblastic leukemia. Cancer Discov 2016;6:664‑79.

Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR,

Katze MG. Into the eye of the cytokine storm. Microbiol Mol

Biol Rev 2012;76:16‑32.

Us D. [Cytokine storm in avian influenza]. Mikrobiyol Bul


Teijaro JR, Walsh KB, Rice S, Rosen H, Oldstone MB. Mapping

the innate signaling cascade essential for cytokine storm during

influenza virus infection. Proc Natl Acad Sci 2014;111:3799‑804.

Wang H, Ma S. The cytokine storm and factors determining the

sequence and severity of organ dysfunction in multiple organ

dysfunction syndrome. Am J Emerg Med 2008;26:711‑5.

Boomer JS, To K, Chang KC, Takasu O, Osborne DF,

Walton AH, et al. Immunosuppression in patients who die of

sepsis and multiple organ failure. JAMA 2011;306:2594‑605.

Liu T, Zhang L, Joo D, Sun S‑C. NF‑κB signaling in

inflammation. Signal Transduct Target Ther 2017;2:1‑9. doi:

1038/sigtrans. 2017.23.

Dash P, Thomas PG. Host detection and the stealthy phenotype

in influenza virus infection. Influenza Pathogenesis and Control.

Vol II. Springer; 2014. p. 121‑47.

Khanmohammadi S, Rezaei N. Role of Toll‐like receptors in the

pathogenesis of COVID‐19. J Med Virol 2021;93:2735‑9.

Onofrio L, Caraglia M, Facchini G, Margherita V, Placido SD,

Buonerba C. Toll‑like receptors and COVID‑19: A two‑faced

story with an exciting ending. Future Sci 2020;6:FSO605.

Zhang Y, Lu Y, Ma L, Cao X, Xiao J, Chen J, et al. Activation

of vascular endothelial growth factor receptor‑3 in macrophages

restrains TLR4‑NF‑κB signaling and protects against endotoxin

shock. Immunity 2014;40:501‑14.

Park S‑J, Youn H‑S. Isoliquiritigenin suppresses the

toll − interleukin‑1 receptor domain‑containing adapter

inducing interferon‑β (TRIF)‑dependent signaling pathway

of toll‑like receptors by targeting TBK1. J Agric Food Chem


O’Neill LA, Bowie AG. The family of five:

TIR‑domain‑containing adaptors in Toll‑like receptor signalling.

Nat Rev Immunol 2007;7:353‑64.

Aboudounya MM, Heads RJ. COVID‑19 and toll‑like receptor

(TLR4): SARS‑CoV‑2 may bind and activate TLR4 to

increase ACE2 expression, facilitating entry and causing

hyperinflammation. Mediators Inflamm 2021;2021:8874339. doi:


Brandão SC, Ramos JdOX, Dompieri LT, Godoi ET,

Figueiredo JL, Sarinho ESC, et al. Is toll‑like receptor 4

involved in the severity of COVID‑19 pathology in patients with

cardiometabolic comorbidities? Cytokine Growth Factor Rev


Bortolotti D, Gentili V, Rizzo S, Schiuma G, Beltrami S,

Strazzabosco G, et al. TLR3 and TLR7 RNA sensor activation

during SARS‑COV‑2 infection. Microorganisms 2021;9:1820.

doi: 10.3390/microorganisms9091820.

Zheng M, Karki R, Williams EP, Yang D, Fitzpatrick E, Vogel P,

et al. TLR2 senses the SARS‑CoV‑2 envelope protein to produce

inflammatory cytokines. Nat Immunol 2021;22:1‑10.

Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R.

Features, Evaluation and Treatment Coronavirus (COVID‑19).

Statpearls: StatPearls Publishing; 2022.

Lu H. Drug treatment options for the 2019‑new

coronavirus (2019‑nCoV). Biosci Trends 2020;14:69‑71.

Zorofchian Moghadamtousi S, Abdul Kadir H, Hassandarvish P,

Tajik H, Abubakar S, Zandi K. A review on antibacterial,

antiviral, and antifungal activity of curcumin. BioMed Res Int 2014;2014. doi: 10.1155/2014/186864.

Chen D‑Y, Shien J‑H, Tiley L, Chiou S‑S, Wang S‑Y,

Chang T‑J, et al. Curcumin inhibits influenza virus infection and

haemagglutination activity. Food Chem 2010;119:1346‑51.

Mathew D, Hsu W‑L. Antiviral potential of curcumin. J Funct

Foods 2018;40:692‑9.

Fan Z, Yao J, Li Y, Hu X, Shao H, Tian X. Anti‑inflammatory

and antioxidant effects of curcumin on acute lung injury in a

rodent model of intestinal ischemia reperfusion by inhibiting the

pathway of NF‑Kb. Int J Clin Exp Pathol 2015;8:3451‑9.

Lubbad A, Oriowo M, Khan I. Curcumin attenuates inflammation

through inhibition of TLR‑4 receptor in experimental colitis. Mol

Cell Biochem 2009;322:127‑35.

Jurenka JS. Anti‑inflammatory properties of curcumin, a major

constituent of Curcuma longa: A review of preclinical and

clinical research. Altern Med Rev 2009;14:141‑53.

Menon VP, Sudheer AR. Antioxidant and anti‑inflammatory

properties of curcumin. The Molecular Targets and Therapeutic Uses

of Curcumin in Health and Disease. Springer; 2007. p. 105‑25.

Ou JL, Mizushina Y, Wang SY, Chuang DY, Nadar M, Hsu WL.

Structure–activity relationship analysis of curcumin analogues on

anti‐influenza virus activity. FEBS J 2013;280:5829‑40.

Yadav V, Mishra K, Singh D, Mehrotra S, Singh V.

Immunomodulatory effects of curcumin. Immunopharmacol

Immunotoxicol 2005;27:485‑97.

Zahedipour F, Hosseini SA, Sathyapalan T, Majeed M,

Jamialahmadi T, Al‐Rasadi K, et al. Potential effects of

curcumin in the treatment of COVID‐19 infection. Phytother Res


Soni VK, Mehta A, Ratre YK, Tiwari AK, Amit A, Singh RP,

et al. Curcumin, a traditional spice component, can hold the

promise against COVID‑19? Eur J Pharmacol 2020;886:173551.

doi: 10.1016/j.ejphar. 2020.173551.

Babaei F, Nassiri‐Asl M, Hosseinzadeh H. Curcumin (a

constituent of turmeric): New treatment option against

COVID‐19. Food Sci Nutr 2020;8:5215‑27.

Rocha FA, de Assis MR. Curcumin as a potential treatment for

COVID‐19. Phytother Res 2020;34:2085‑7.

Wang S, Lv W, Zhang H, Liu Y, Li L, Jefferson JR, et al. Aging

exacerbates impairments of cerebral blood flow autoregulation

and cognition in diabetic rats. Geroscience 2020;42:1387‑410.

Velavan TP, Meyer CG. The Covid‑19 epidemic. Trop Med Int

Health 2020;25:278‑80.

Okabayashi T, Kariwa H, Yokota Si, Iki S, Indoh T, Yokosawa N,

et al. Cytokine regulation in SARS coronavirus infection compared

to other respiratory virus infections. J Med Virol 2006;78:417‑24.

Yi Y, Lagniton PN, Ye S, Li E, Xu R‑H. COVID‑19: What has

been learned and to be learned about the novel coronavirus

disease. Int J Biol Sci 2020;16:1753‑66.

Thiel V, Weber F. Interferon and cytokine responses to

SARS‑coronavirus infection. Cytokine Growth Factor Rev


Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus

infections and immune responses. J Med Virol 2020;92:424‑32.

Wang S, Zhang Y, Lui S, Peng H, Mackey V. Coronaviruses

and the associated potential therapeutics for the viral infections.

J Infect Dis Ther 2020;8. Available from: https://www.





Viral‑Infections.pdf. [Last accessed on 2022 Mar 30].

Ye Q, Wang B, Mao J. Cytokine storm in COVID‑19 and

treatment. J Infect 2020;80:607‑13.

Ma L, Song K, Huang Y. Coronavirus disease 2019 (COVID‑19)

and cardiovascular complications. J Cardiothorac Vasc Anesth


Minoia F, Davì S, Alongi A, Ravelli A. Criteria for Cytokine

Storm Syndromes. Cytokine Storm Syndrome. Springer Berlin/

Heidelberg; 2019. p. 61‑79.

Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. COVID‑19:

Pathogenesis, cytokine storm and therapeutic potential of

interferons. Cytokine Growth Factor Rev 2020;85:104502. doi:

1016/j.meegid. 2020.104502.

Schulert GS, Zhang K. Genetics of Acquired Cytokine Storm

Syndromes. Cytokine Storm Syndrome. Springer Berlin/

Heidelberg; 2019. p. 113‑29.

Ye Q, Wang B, Mao J. The pathogenesis and treatment of

theCytokine Storm’in COVID‑19. J Infect 2020;80:607‑13.

Gupta KK, Khan MA, Singh SK. Constitutive inflammatory

cytokine storm: A major threat to human health. J Interferon

Cytokine Res 2020;40:19‑23.

Kawai T, Akira S. Signaling to NF‑κB by Toll‑like receptors.

Trends Mol Med 2007;13:460‑9.

Wang Q‑W, Su Y, Sheng J‑T, Gu L‑M, Zhao Y, Chen X‑X,

et al. Anti‑influenza a virus activity of rhein through regulating

oxidative stress, TLR4, Akt, MAPK, and NF‑κB signal

pathways. PloS One 2018;13:e0191793. doi: 10.1371/journal.

pone. 0191793.

Planz O. Influenza viruses and intracellular signalling pathways.

Berl Munch Tierarztl Wochenschrift 2006;119:101‑11.

Walsh KB, Teijaro JR, Wilker PR, Jatzek A, Fremgen DM,

Das SC, et al. Suppression of cytokine storm with a sphingosine

analog provides protection against pathogenic influenza virus.

Proc Natl Acad Sci 2011;108:12018‑23.

Xi‑zhi JG, Thomas PG. New fronts emerge in the

influenza cytokine storm. Semin Immunopathol Berlin/

Heidelberg 2017;39:541‑50.

Zhang X, Wu K, Wang D, Yue X, Song D, Zhu Y, et al.

Nucleocapsid protein of SARS‑CoV activates interleukin‑6

expression through cellular transcription factor NF‑κB. Virology


DeDiego ML, Nieto‑Torres JL, Jimenez‑Guardeño JM,

Regla‑Nava JA, Castaño‑Rodriguez C, Fernandez‑Delgado R,

et al. Coronavirus virulence genes with main focus on

SARS‑CoV envelope gene. Virus Res 2014;194:124‑37.

Dosch SF, Mahajan SD, Collins AR. SARS coronavirus spike

protein‑induced innate immune response occurs via activation of

the NF‑κB pathway in human monocyte macrophages in vitro.

Virus Res 2009;142:19‑27.

DeDiego ML, Nieto‑Torres JL, Regla‑Nava JA,

Jimenez‑Guardeño JM, Fernandez‑Delgado R, Fett C, et al.

Inhibition of NF‑κB‑mediated inflammation in severe acute

respiratory syndrome coronavirus‑infected mice increases

survival. J Virol 2014;88:913‑24.

Yuk J‑M, Jo E‑K. Toll‑like receptors and innate immunity.

J Bacteriol Virol 2011;41:225‑35.

Trinchieri G, Sher A. Cooperation of Toll‑like receptor signals in

innate immune defence. Nat Rev Immunol 2007;7:179‑90.

Turvey SE, Broide DH. Innate immunity. J Allergy Clin Immunol


Leaphart CL, Cavallo J, Gribar SC, Cetin S, Li J, Branca MF,

et al. A critical role for TLR4 in the pathogenesis of necrotizing

enterocolitis by modulating intestinal injury and repair.

J Immunol 2007;179:4808‑20.

Greenhill CJ, Rose‑John S, Lissilaa R, Ferlin W, Ernst M, Hertzog PJ, et al. IL‑6 trans‑signaling modulates

TLR4‑dependent inflammatory responses via STAT3. J Immunol


Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H,

et al. Role of adaptor TRIF in the MyD88‑independent toll‑like

receptor signaling pathway. Science 2003;301:640‑3.

Takeda K, Akira S. TLR signaling pathways. Semin Immunol

Berlin/Heidelberg 2004;16:3‑9.

Kircheis R, Haasbach E, Lueftenegger D, Heyken WT, Ocker M,

Planz O. NF‑κB pathway as a potential target for treatment of

critical stage COVID‑19 patients. Front Immunol 2020;11:3446.

Kandasamy M. NF‑κB signalling as a pharmacological target

in COVID‑19: Potential roles for IKKβ inhibitors. Naunyn

Schmiedebergs Arch Pharmacol 2021;394:561‑7.

Cheng Y‑F, Guo L, Xie Y‑S, Liu Y‑S, Zhang J, Wu Q‑W, et al.

Curcumin rescues aging‑related loss of hippocampal synapse

input specificity of long term potentiation in mice. Neurochem

Res 2013;38:98‑107.

Zhao J, Yu S, Zheng W, Feng G, Luo G, Wang L, et al.

Curcumin improves outcomes and attenuates focal cerebral

ischemic injury via antiapoptotic mechanisms in rats. Neurochem

Res 2010;35:374‑9.

Panchal HD, Vranizan K, Lee CY, Ho J, Ngai J, Timiras PS.

Early anti‑oxidative and anti‑proliferative curcumin effects on

neuroglioma cells suggest therapeutic targets. Neurochem Res


Cole GM, Teter B, Frautschy SA. Neuroprotective effects of

curcumin. The Molecular Targets and Therapeutic Uses of

Curcumin in Health and Disease. Springer; Berlin/Heidelberg

p. 197‑212.

Motaghinejad M, Karimian M, Motaghinejad O, Shabab B,

Yazdani I, Fatima S. Protective effects of various dosage of

curcumin against morphine induced apoptosis and oxidative stress

in rat isolated hippocampus. Pharmacol Rep 2015;67:230‑5.

Shojaii A, Motaghinejad M, Norouzi S, Motevalian M.

Evaluation of anti‑inflammatory and analgesic activity of the

extract and fractions of Astragalus hamosus in animal models.

Iran J Pharm Res 2015;14:263‑9.

Aggarwal BB, Harikumar KB. Potential therapeutic effects of

curcumin, the anti‑inflammatory agent, against neurodegenerative,

cardiovascular, pulmonary, metabolic, autoimmune and neoplastic

diseases. Int J Biochem Cell Biol 2009;41:40‑59.

Darvesh AS, Carroll RT, Bishayee A, Novotny NA,

Geldenhuys WJ, Van der Schyf CJ. Curcumin and

neurodegenerative diseases: A perspective. Expert Opin Invest

Drugs 2012;21:1123‑40.

Motaghinejad M, Motevalian M, Fatima S, Hashemi H,

Gholami M. Curcumin confers neuroprotection against

alcohol‑induced hippocampal neurodegeneration via

CREB‑BDNF pathway in rats. Biomed Pharmacother


Huang H‑C, Chang P, Dai X‑L, Jiang Z‑F. Protective effects

of curcumin on amyloid‑β‑induced neuronal oxidative damage.

Neurochem Res 2012;37:1584‑97.

Akram M, Shahab‑Uddin AA, Usmanghani K, Hannan A,

Mohiuddin E, Asif M. Curcuma longa and curcumin: A review

article. Rom J Biol Plant Biol 2010;55:65‑70.

Xiao X, Yang M, Sun D, Sun S. Curcumin protects

against sepsis‑induced acute lung injury in rats. J Surg Res


Sandur SK, Ichikawa H, Pandey MK, Kunnumakkara AB,

Sung B, Sethi G, et al. Role of pro‑oxidants and

antioxidants in the anti‑inflammatory and apoptotic effects

of curcumin (diferuloylmethane). Free Radic Biol Med


Yang M, Lee G, Si J, Lee S‑J, You HJ, Ko G. Curcumin shows

antiviral properties against norovirus. Molecules 2016;21:1401.

doi: 10.3390/molecules21101401.

Nandakumar DN, Nagaraj VA, Vathsala PG, Rangarajan P,

Padmanaban G. Curcumin‑artemisinin combination therapy for

malaria. Antimicro Agents Chemother 2006;50:1859‑60.

Isacchi B, Bergonzi MC, Grazioso M, Righeschi C, Pietretti A,

Severini C, et al. Artemisinin and artemisinin plus curcumin

liposomal formulations: Enhanced antimalarial efficacy against

Plasmodium berghei‑infected mice. Eur J Pharm Biopharm


Rao TS, Basu N, Siddiqui H. Anti‑inflammatory activity of

curcumin analogues. Indian J Med Res 2013;137:574‑8.

Araujo C, Leon L. Biological activities of curcuma longa L.

Mem Inst Oswaldo Cruz 2001;96:723‑8.

Sordillo PP, Helson L. Curcumin suppression of cytokine

release and cytokine storm. A potential therapy for patients with

Ebola and other severe viral infections. In Vivo 2015;29:1‑4.

Ni H, Jin W, Zhu T, Wang J, Yuan B, Jiang J, et al. Curcumin

modulates TLR4/NF‑κB inflammatory signaling pathway

following traumatic spinal cord injury in rats. J Spinal Cord

Med 2015;38:199‑206.

Dai J, Gu L, Su Y, Wang Q, Zhao Y, Chen X, et al. Inhibition

of curcumin on influenza A virus infection and influenzal

pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and

NF‑κB pathways. Int Immunopharmacol 2018;54:177‑87.

Strimpakos AS, Sharma RA. Curcumin: Preventive and

therapeutic properties in laboratory studies and clinical trials.

Antioxid Redox Signal 2008;10:511‑46.