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2000
Volume 19, Issue 1
  • ISSN: 2772-2708
  • E-ISSN: 2772-2716

Abstract

Carrageenan, a naturally occurring polysaccharide derived from red seaweed, has been utilized extensively in the food industry as a stabilizer, thickener, and emulsifier due to its unique gel-forming properties. This versatile compound exists in various forms, including kappa, iota, and lambda, each with distinct characteristics suitable for different applications. Its widespread use as a food additive has raised concerns regarding its safety, particularly its potential inflammatory effects on the gastrointestinal tract. While carrageenan has been deemed safe for consumption by regulatory agencies in small amounts, studies have suggested its association with intestinal inflammation and gastrointestinal disturbances, particularly in susceptible individuals. Animal models, including rodents and non-human primates, have been employed to investigate the inflammatory response induced by carrageenan ingestion. These models have provided valuable insights into the molecular mechanisms underlying its pro-inflammatory properties. At the molecular level, carrageenan is believed to trigger inflammation by activating toll-like receptor 4 (TLR4) signaling pathways, leading to the production of pro-inflammatory cytokines and the recruitment of immune cells to the site of exposure. Furthermore, carrageenan-induced inflammation may disrupt the intestinal barrier function, facilitating the translocation of luminal antigens and exacerbating immune responses. This review provides a comprehensive examination of the current understanding of carrageenan's role in inflammation, encompassing its diverse applications in the food industry, safety concerns, experimental findings from animal models, and molecular mechanisms underlying its pro-inflammatory effects.

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References

  1. TobacmanJ.K. Review of harmful gastrointestinal effects of carrageenan in animal experiments.Environ. Health Perspect.20011091098399410.1289/ehp.0110998311675262
    [Google Scholar]
  2. BaydiZ. LimamiY. KhalkiL. ZaidN. NayaA. MtairagE.M. OudghiriM. ZaidY. An update of research animal models of inflammatory bowel disease.Sci World J2021202111210.1155/2021/747954034938152
    [Google Scholar]
  3. PadovaniB.N. Abrantes do AmaralM. FéneroC.M. ParedesL.C. Boturra de BarrosG.J. XavierI.K. HiyaneM.I. GhirottoB. FeijóoC.G. Saraiva CâmaraN.O. TakiishiT. Different wild type strains of zebrafish show divergent susceptibility to TNBS-induced intestinal inflammation displaying distinct immune cell profiles.Curr Res Immunol20223132210.1016/j.crimmu.2021.12.00335496825
    [Google Scholar]
  4. ChudnovskiyA. PasqualG. VictoraG.D. Studying interactions between dendritic cells and T cells in vivo.Curr. Opin. Immunol.201958243010.1016/j.coi.2019.02.00230884422
    [Google Scholar]
  5. LimamiY. LegerD.Y. LiagreB. PécoutN. VianaM. Ibuprofen-loaded calcium phosphate granules: A new bone substitute for local relieving symptoms of osteoarthritis.Eur. J. Pharm. Sci.202115810567910.1016/j.ejps.2020.10567933346009
    [Google Scholar]
  6. MarhoumeF.Z. AboufatimaR. ZaidY. LimamiY. DuvalR.E. LaadraouiJ. BelbachirA. ChaitA. BagriA. Antioxidant and polyphenol-rich ethanolic extract of Rubia tinctorum L. prevents urolithiasis in an ethylene glycol experimental model in rats.Molecules2021264100510.3390/molecules2604100533672875
    [Google Scholar]
  7. NdayambajeM. WahnouH. SowM. ChgariO. HabyarimanaT. KarkouriM. LimamiY. NayaA. OudghiriM. Exploring the multifaceted effects of Ammi visnaga: Subchronic toxicity, antioxidant capacity, immunomodulatory, and anti-inflammatory activities.J Toxicol Environ Health A202487415016510.1080/15287394.2023.2289430
    [Google Scholar]
  8. BouchabH. EssadekS. El KamouniS. MoustaidK. EssamadiA. AndreolettiP. Cherkaoui-MalkiM. El KebbajR. NasserB. AAntioxidant effects of argan oil and olive oil against iron-induced oxidative stress: In vivo and in vitro approaches.Molecules20232815592410.3390/molecules28155924
    [Google Scholar]
  9. Tahri-JouteyM. SaihF.E. El KebbajR. GondcailleC. VamecqJ. LatruffeN. LizardG. SavaryS. NasserB. Cherkaoui-MalkiM. AndreolettiP. Protective effect of nopal cactus (Opuntia ficus-indica) seed oil against short-term lipopolysaccharides-induced inflammation and peroxisomal functions dysregulation in mouse brain and liver.Int. J. Mol. Sci.202223191184910.3390/ijms23191184936233157
    [Google Scholar]
  10. BouchabH. IshaqA. El KebbajR. NasserB. SaretzkiG. Protective effect of argan oil on DNA damage in vivo and in vitro.Biomarkers202126542543310.1080/1354750X.2021.1905068
    [Google Scholar]
  11. BhattacharyyaS. DudejaP.K. TobacmanJ.K. Tumor necrosis factor α-induced inflammation is increased but apoptosis is inhibited by common food additive carrageenan.J. Biol. Chem.201028550395113952210.1074/jbc.M110.15968120937806
    [Google Scholar]
  12. GuoZ. WeiY. ZhangY. XuY. ZhengL. ZhuB. YaoZ. Carrageenan oligosaccharides: A comprehensive review of preparation, isolation, purification, structure, biological activities and applications.Algal Res.20226110259310.1016/j.algal.2021.102593
    [Google Scholar]
  13. UdoT. MummaletiG. MohanA. SinghR.K. KongF. Current and emerging applications of carrageenan in the food industry.Food Res. Int.2023173Pt 211336910.1016/j.foodres.2023.11336937803710
    [Google Scholar]
  14. NicklinS. MillerK. Intestinal uptake and immunological effects of carrageenan—current concepts.Food Addit. Contam.19896442543610.1080/026520389093738012676614
    [Google Scholar]
  15. BorsaniB. De SantisR. PericoV. PenaginiF. PendezzaE. DililloD. BosettiA. ZuccottiG.V. D’AuriaE. The role of carrageenan in inflammatory bowel diseases and allergic reactions: Where do we stand?Nutrients20211310340210.3390/nu1310340234684400
    [Google Scholar]
  16. KomisarskaP. PinyosinwatA. SaleemM. SzczukoM. Carrageenan as a potential factor of inflammatory bowel diseases.Nutrients2024169136710.3390/nu1609136738732613
    [Google Scholar]
  17. LuY.C. YehW.C. OhashiP.S. LPS/TLR4 signal transduction pathway.Cytokine200842214515110.1016/j.cyto.2008.01.00618304834
    [Google Scholar]
  18. ParkB.S. LeeJ.O. Recognition of lipopolysaccharide pattern by TLR4 complexes.Exp. Mol. Med.20134512e66e6610.1038/emm.2013.9724310172
    [Google Scholar]
  19. MukherjeeS. KarmakarS. BabuS.P. TLR2 and TLR4 mediated host immune responses in major infectious diseases: A review.Braz J Infect Dis.201620219320410.1016/j.bjid.2015.10.011
    [Google Scholar]
  20. MolteniM. GemmaS. RossettiC. The role of toll-like receptor 4 in infectious and noninfectious inflammation.Mediators Inflamm.201620161910.1155/2016/697893627293318
    [Google Scholar]
  21. VaureC.Ã. LiuY. A comparative review of toll-like receptor 4 expression and functionality in different animal species.Front. Immunol.2014531610.3389/fimmu.2014.0031625071777
    [Google Scholar]
  22. HuangQ.Q. PopeR.M. The role of Toll-like receptors in rheumatoid arthritis.Curr. Rheumatol. Rep.200911535736410.1007/s11926‑009‑0051‑z19772831
    [Google Scholar]
  23. LiH. SunB. Toll‐like receptor 4 in atherosclerosis.J. Cell. Mol. Med.2007111889510.1111/j.1582‑4934.2007.00011.x17367503
    [Google Scholar]
  24. RogeroM. CalderP. Obesity, inflammation, toll-like receptor 4 and fatty acids.Nutrients201810443210.3390/nu1004043229601492
    [Google Scholar]
  25. KawaiT. AutieriM.V. ScaliaR. Adipose tissue inflammation and metabolic dysfunction in obesity.Am. J. Physiol. Cell Physiol.20213203C375C39110.1152/ajpcell.00379.202033356944
    [Google Scholar]
  26. McKernanK. VargheseM. PatelR. SingerK. Role of TLR4 in the induction of inflammatory changes in adipocytes and macrophages.Adipocyte20209121222210.1080/21623945.2020.176067432403975
    [Google Scholar]
  27. HeidariA. YazdanpanahN. RezaeiN. The role of Toll-like receptors and neuroinflammation in Parkinson’s disease.J. Neuroinflammat202219113510.1186/s12974‑022‑02496‑w35668422
    [Google Scholar]
  28. DiSabatoD.J. QuanN. GodboutJ.P. Neuroinflammation: The devil is in the details.J. Neurochem.2016139Suppl. 213615310.1111/jnc.1360726990767
    [Google Scholar]
  29. BoukhvalovaM.S. KastrukoffL. BlancoJ.C.G. Alzheimer’s disease and multiple sclerosis: A possible connection through the viral demyelinating neurodegenerative trigger (vDENT).Front. Aging Neurosci.202315120485210.3389/fnagi.2023.120485237396655
    [Google Scholar]
  30. LiJ. YangF. WeiF. RenX. The role of toll-like receptor 4 in tumor microenvironment.Oncotarget2017839666566666710.18632/oncotarget.1910529029545
    [Google Scholar]
  31. Urban-WojciukZ. KhanM.M. OylerB.L. FåhraeusR. Marek-TrzonkowskaN. Nita-LazarA. HuppT.R. GoodlettD.R. The role of TLRs in anti-cancer immunity and tumor rejection.Front. Immunol.201910238810.3389/fimmu.2019.0238831695691
    [Google Scholar]
  32. BorthakurA. BhattacharyyaS. DudejaP.K. TobacmanJ.K. Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells.Am. J. Physiol. Gastrointest. Liver Physiol.20072923G829G83810.1152/ajpgi.00380.200617095757
    [Google Scholar]
  33. UllahM.O. SweetM.J. MansellA. KellieS. KobeB. TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target.J. Leukoc. Biol.20161001274510.1189/jlb.2RI1115‑531R27162325
    [Google Scholar]
  34. LiuT. ZhangL. JooD. SunS.C. NF-κB signaling in inflammation.Signal Transduct. Target. Ther.2017211702310.1038/sigtrans.2017.2329158945
    [Google Scholar]
  35. TravisM.A. SheppardD. TGF-β activation and function in immunity.Annu. Rev. Immunol.2014321518210.1146/annurev‑immunol‑032713‑12025724313777
    [Google Scholar]
  36. BarthC.R. FunchalG.A. LuftC. de OliveiraJ.R. PortoB.N. DonadioM.V.F. Carrageenan‐induced inflammation promotes ROS generation and neutrophil extracellular trap formation in a mouse model of peritonitis.Eur. J. Immunol.201646496497010.1002/eji.20154552026786873
    [Google Scholar]
  37. GuillotinF. FortierM. PortesM. DematteiC. MoustyE. NouvellonE. MercierE. CheaM. LetouzeyV. GrisJ.C. BouvierS. Vital NETosis vs. suicidal NETosis during normal pregnancy and preeclampsia.Front. Cell Dev. Biol.202310109903810.3389/fcell.2022.109903836684420
    [Google Scholar]
  38. LopesA.H. SilvaR.L. FonsecaM.D. GomesF.I. MaganinA.G. RibeiroL.S. MarquesL.M.M. CunhaF.Q. Alves-FilhoJ.C. ZamboniD.S. LopesN.P. FranklinB.S. GombaultA. RamalhoF.S. QuesniauxV.F.J. CouillinI. RyffelB. CunhaT.M. Molecular basis of carrageenan-induced cytokines production in macrophages.Cell Commun. Signal.202018114110.1186/s12964‑020‑00621‑x32894139
    [Google Scholar]
  39. LiJ. AipireA. LiJ. ZhuH. WangY. GuoW. LiX. YangJ. LiuC. λ-Carrageenan improves the antitumor effect of dendritic cellbased vaccine.Oncotarget2017818299963000710.18632/oncotarget.1561028404904
    [Google Scholar]
  40. VargaftigB.B. FouqueF. ChignardM. DumareyC. Carrageenan-induced activation of human platelets is independent of phospholipase A2 and of formation of thromboxanes.J. Pharm. Pharmacol.201132174074510.1111/j.2042‑7158.1980.tb13058.x6110720
    [Google Scholar]
  41. HatmiM. RandonJ. FailiA. VargaftigB.B. Carrageenan‐induced activation of human platelets is dependent on the phospholipase C Pathway.Br. J. Haematol.199383227027510.1111/j.1365‑2141.1993.tb08282.x8457475
    [Google Scholar]
  42. MyersM.J. DeaverC.M. LewandowskiA.J. Molecular mechanism of action responsible for carrageenan-induced inflammatory response.Mol. Immunol.2019109384210.1016/j.molimm.2019.02.02030851635
    [Google Scholar]
  43. HernándezC. SeguraR.M. FonollosaA. CarrascoE. FranciscoG. SimóR. Interleukin‐8, monocyte chemoattractant protein‐1 and IL‐10 in the vitreous fluid of patients with proliferative diabetic retinopathy.Diabet. Med.200522671972210.1111/j.1464‑5491.2005.01538.x15910622
    [Google Scholar]
  44. SinghS. AnshitaD. RavichandiranV. MCP-1: Function, regulation, and involvement in disease.Int. Immunopharmacol.2021101Pt B10759810.1016/j.intimp.2021.10759834233864
    [Google Scholar]
  45. ShangQ. SunW. ShanX. JiangH. CaiC. HaoJ. LiG. YuG. Carrageenan-induced colitis is associated with decreased population of anti-inflammatory bacterium, Akkermansia muciniphila, in the gut microbiota of C57BL/6J mice.Toxicol. Lett.2017279879510.1016/j.toxlet.2017.07.90428778519
    [Google Scholar]
  46. MiY. ChinY.X. CaoW.X. ChangY.G. LimP.E. XueC.H. TangQ.J. Native κ-carrageenan induced-colitis is related to host intestinal microecology.Int. J. Biol. Macromol.202014728429410.1016/j.ijbiomac.2020.01.07231926226
    [Google Scholar]
  47. MarshallE.A. TelkarN. LamW.L. Functional role of the cancer microbiome in the solid tumour niche.Curr Res Immunol202121610.1016/j.crimmu.2021.01.00135492394
    [Google Scholar]
  48. WuW. ZhouJ. XuanR. ChenJ. HanH. LiuJ. NiuT. ChenH. WangF. Dietary κ-carrageenan facilitates gut microbiota-mediated intestinal inflammation.Carbohydr. Polym.202227711883010.1016/j.carbpol.2021.11883034893247
    [Google Scholar]
  49. ForderA. StewartG.L. TelkarN. LamW.L. GarnisC. New insights into the tumour immune microenvironment of nasopharyngeal carcinoma.Curr Res Immunol2022322222710.1016/j.crimmu.2022.08.00936118267
    [Google Scholar]
  50. McKimJ.M.Jr BaasH. RiceG.P. WilloughbyJ.A.Sr WeinerM.L. BlakemoreW. Effects of carrageenan on cell permeability, cytotoxicity, and cytokine gene expression in human intestinal and hepatic cell lines.Food Chem. Toxicol.20169611010.1016/j.fct.2016.07.00627424122
    [Google Scholar]
  51. AshrafS. MappP.I. ShahtaheriS.M. WalshD.A. Effects of carrageenan induced synovitis on joint damage and pain in a rat model of knee osteoarthritis.Osteoarthritis Cartilage201826101369137810.1016/j.joca.2018.07.00130031926
    [Google Scholar]
  52. EssadekS. GondcailleC. SavaryS. SamadiM. VamecqJ. LizardG. El KebbajR. LatruffeN. BenaniA. NasserB. Cherkaoui-MalkiM. AndreolettiP. Two argan oil phytosterols, schottenol and spinasterol, attenuate oxidative stress and restore lps-dysregulated peroxisomal functions in Acox1−/− and wild-type BV-2 microglial cells.Antioxidants202312116810.3390/antiox1201016836671029
    [Google Scholar]
  53. SammonsM.J. RavalP. DaveyP.T. RogersD. ParsonsA.A. BinghamS. Carrageenan-induced thermal hyperalgesia in the mouse: Role of nerve growth factor and the mitogen-activated protein kinase pathway.Brain Res.20008761-2485410.1016/S0006‑8993(00)02596‑810973592
    [Google Scholar]
  54. KocherL. AntonF. ReehP.W. HandwerkerH.O. The effect of carrageenan-induced inflammation on the sensitivity of unmyelinated skin nociceptors in the rat.Pain198729336337310.1016/0304‑3959(87)90051‑03614971
    [Google Scholar]
  55. ArunO. CanbayO. CelebiN. SahinA. KonanA. AtillaP. AyparU. The analgesic efficacy of intra-articular acetaminophen in an experimental model of carrageenan-induced arthritis.Pain Res. Manag.2013185e63e6710.1155/2013/14839224093120
    [Google Scholar]
  56. NeugebauerV. Arthritis Model, Kaolin-Carrageenan-Induced Arthritis (Knee).Encyclopedia of Pain. GebhartG.F. SchmidtR.F. Berlin, HeidelbergSpringer Berlin Heidelberg201319019610.1007/978‑3‑642‑28753‑4_283
    [Google Scholar]
  57. SurB. KangS. KimM. OhS. Inhibition of carrageenan/kaolin-induced arthritis in rats and of inflammatory cytokine expressions in human IL-1β-stimulated fibroblast-like synoviocytes by a benzylideneacetophenone derivative.Inflammation201942392893610.1007/s10753‑018‑0947‑830565030
    [Google Scholar]
  58. GhorbanzadehB. MansouriM.T. HemmatiA.A. NaghizadehB. MardS.A. RezaieA. A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats.Indian J. Pharmacol.201547329229810.4103/0253‑7613.15712726069367
    [Google Scholar]
  59. Van DammeN. Van HeckeA. RemueE. Van den BusscheK. MooreZ. GefenA. VerhaegheS. BeeckmanD. Physiological processes of inflammation and edema initiated by sustained mechanical loading in subcutaneous tissues: A scoping review.Wound Repair Regen.202028224226510.1111/wrr.12777
    [Google Scholar]
  60. Vargas-RuizR. Montiel-RuizR.M. Herrera-RuizM. González-CortazarM. Ble-GonzálezE.A. Jiménez-AparicioA.R. Jiménez-FerrerE. ZamilpaA. Effect of phenolic compounds from Oenothera rosea on the kaolin-carrageenan induced arthritis model in mice.J. Ethnopharmacol.202025311271110.1016/j.jep.2020.11271132097698
    [Google Scholar]
  61. SurB. KimM. VillaT. OhS. Phytoceramide alleviates the carrageenan/kaolin-induced arthritic symptoms by modulation of inflammation.Biomol. Ther.202331553654310.4062/biomolther.2023.03137381800
    [Google Scholar]
  62. WahnouH. NdayambajeM. OuadghiriZ. BenayadS. ElattarH. ChgariO. NayaA. ZaidY. OudghiriM. Artemisia herba-alba: Antioxidant capacity and efficacy in preventing chronic arthritis in vivo.Inflammopharmacology20243231855187010.1007/s10787‑024‑01463‑638607503
    [Google Scholar]
  63. ZhangY.Q. TsaiY.C. MonieA. HungC.F. WuT.C. Carrageenan as an adjuvant to enhance peptide-based vaccine potency.Vaccine201028325212521910.1016/j.vaccine.2010.05.06820541583
    [Google Scholar]
  64. ChenX. HanW. ZhaoX. TangW. WangF. Epirubicin-loaded marine carrageenan oligosaccharide capped gold nanoparticle system for pH-triggered anticancer drug release.Sci. Rep.201991675410.1038/s41598‑019‑43106‑931043709
    [Google Scholar]
  65. WakabayashiK. InagakiT. FujimotoY. FukudaY. Induction by degraded carrageenan of colorectal tumors in rats.Cancer Lett.19784317117610.1016/S0304‑3835(78)94237‑4647659
    [Google Scholar]
  66. HassimottoN.M.A. MoreiraV. NascimentoN.G. SoutoP.C.M.C. TeixeiraC. LajoloF.M. Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside.BioMed Res. Int.2013201311010.1155/2013/14671623484081
    [Google Scholar]
  67. de Siqueira PatriotaL.L. de Brito Marques RamosD. e SilvaM.G. dos SantosA.C.L.A. SilvaY.A. PaivaP.M.G. PontualE.V. de AlbuquerqueL.P. MendesR.L. NapoleãoT.H. Inhibition of Carrageenan-Induced Acute Inflammation in Mice by the Microgramma vacciniifolia Frond Lectin (MvFL).Polymers2022148160910.3390/polym1408160935458359
    [Google Scholar]
  68. AlvesC.F. AlvesV.B.F. de AssisI.P. Clemente-NapimogaJ.T. Uber-BucekE. Dal-SeccoD. CunhaF.Q. RehderV.L.G. NapimogaM.H. Anti-inflammatory activity and possible mechanism of extract from <I>Mikania laevigata</I> in carrageenan-induced peritonitis.J. Pharm. Pharmacol.20096181097110410.1211/jpp/61.08.001419703354
    [Google Scholar]
  69. HagimoriM. KamiyaS. YamaguchiY. ArakawaM. Improving frequency of thrombosis by altering blood flow in the carrageenan-induced rat tail thrombosis model.Pharmacol. Res.200960432032310.1016/j.phrs.2009.04.01019394423
    [Google Scholar]
  70. YokomoriR. ShiraiT. TsukijiN. OishiS. SasakiT. TakanoK. Suzuki-InoueK. C-type lectin-like receptor-2 (CLEC-2) is a key regulator of kappa-carrageenan-induced tail thrombosis model in mice.Platelets2023341228194110.1080/09537104.2023.228194138010137
    [Google Scholar]
  71. ZengS. YiR. TanF. SunP. ChengQ. ZhaoX. Lactobacillus plantarum HFY05 Attenuates carrageenan-induced thrombosis in mice by regulating NF-κB pathway-associated inflammatory responses.Front. Nutr.2022981389910.3389/fnut.2022.813899
    [Google Scholar]
  72. ArslanR. BorZ. BektasN. MeriçliA.H. OzturkY. Antithrombotic effects of ethanol extract of Crataegus orientalis in the carrageenan-induced mice tail thrombosis model.Thromb. Res.2011127321021310.1016/j.thromres.2010.11.02821183208
    [Google Scholar]
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  • Article Type:
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Keyword(s): Animal models; arthritis; cancer; carrageenan; colitis; inflammation; pain; peritonitis; thrombosis; TLR4
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