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Crocin restores the balance of Th1/Th2 immune cell response in ConA-treated human lymphocytes

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Abstract

Background

Following antigen stimulation, naive CD4+ T cells differentiate into different T helper (Th) subsets characterized by lineage-specific transcriptional factors and cytokines. The balance between cytokines from Th1 and Th2 cells is disrupted in autoimmune disorders, asthma, and allergic reactions. Crocin, the major carotenoid of saffron, has anti-inflammatory properties. We investigated crocin modifying effects on the human lymphocytes proliferation and Th1/Th2 balance as a possible mechanism of its anti-inflammatory effects.

Methods

The human peripheral blood mononuclear cells were isolated using Ficoll density gradient centrifugation. MTT was used to evaluate the effect of 72-h treatment with different concentrations of crocin with or without ConA on lymphocytes proliferation. INF-γ/IL-4 cytokine secretion and T-bet/GATA-3 transcription factor expression ratios (as indicators of Th1/Th2 response status) were measured in non-stimulated and ConA-stimulated cells in the presence or absence of crocin by ELISA and RT-qPCR methods, respectively.

Results

The results showed crocin at a concentration of 50 μM and higher was toxic for human lymphocytes, and at a non-toxic concentration of 25 µM, it did not affect cell proliferation. The ratio of T-bet/GATA-3 and INF-γ/IL-4 was higher in the culture supernatant of ConA-stimulated cells compared to non-stimulated ones. Crocin-treated cells showed slightly lower T-bet/GATA-3 and INF-γ/IL-4 ratios compared to untreated cells. Crocin (25 μM) was also able to restore the increased ratio of Th1/Th2 immune response induced by ConA.

Conclusions

Crocin can alleviate inflammatory-stimulant effects of ConA on human lymphocytes by decreasing T-bet/GATA-3 and INF-γ/IL-4 ratios, which are indicative of restoring the balance of Th1/Th2 responses.

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Abbreviations

ConA:

Concanavalin A

Dex:

Dexamethasone

GATA-3:

GATA-binding protein 3

IFN-γ:

Interferon-γ

IL:

Interleukin

IRI:

Ischemia–reperfusion injury

OD:

Optical density

PBMNCs:

Peripheral Blood Mononuclear Cells

STAT:

Signaling transducer and activator of transcription

T-bet:

T-box protein expressed in T cells

Tfh:

T follicular helper

Th:

T helper

Ct:

Cycle threshold

TNF-α:

Tumor necrosis factor-α

References

  1. Zhu J. T helper cell differentiation, heterogeneity, and plasticity. Cold Spring Harb Perspect Biol. 2018;10:a030338.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2009;28:445–89.

    Article  CAS  Google Scholar 

  3. van Beek JJ, Rescigno M, Lugli E. A fresh look at the T helper subset dogma. Nat Immunol. 2021;22:104–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74:5–17.

    Article  CAS  PubMed  Google Scholar 

  5. Crane IJ, Forrester JV. Th1 and Th2 lymphocytes in autoimmune disease. Crit Rev Immunol. 2005;25:75–102.

    Article  CAS  PubMed  Google Scholar 

  6. Hasegawa T, Uga H, Mori A, Kurata H. Increased serum IL-17A and Th2 cytokine levels in patients with severe uncontrolled asthma. Eur Cytokine Netw. 2017;28:8–18.

    Article  CAS  PubMed  Google Scholar 

  7. Asayama K, Kobayashi T, D’Alessandro-Gabazza CN, Toda M, Yasuma T, Fujimoto H, et al. Protein S protects against allergic bronchial asthma by modulating Th1/Th2 balance. Allergy. 2020;75:2267–78.

    Article  CAS  PubMed  Google Scholar 

  8. Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH. Distinct effects of T-bet in TH1 lineage commitment and IFN-γ production in CD4 and CD8 T cells. Science. 2002;295:338–42.

    Article  CAS  PubMed  Google Scholar 

  9. Swain SL, Weinberg AD, English M, Huston G. IL-4 directs the development of Th2-like helper effectors. J Immunol. 1990;145:3796–806.

    CAS  PubMed  Google Scholar 

  10. Le Gros G, Ben-Sasson SZ, Seder R, Finkelman FD, Paul WE. Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med. 1990;172:921–9.

    Article  PubMed  Google Scholar 

  11. Cohen S. Cytokine profile data. Immunol Today. 2000;21:199.

    Article  CAS  PubMed  Google Scholar 

  12. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003;8:223–46.

    PubMed  Google Scholar 

  13. Wambre E, Bajzik V, DeLong JH, O’Brien K, Nguyen Q-A, Speake C, et al. A phenotypically and functionally distinct human TH2 cell subpopulation is associated with allergic disorders. Sci Transl Med. 2017. https://doi.org/10.1126/scitranslmed.aam9171.

    Article  PubMed  PubMed Central  Google Scholar 

  14. O’Grady JG. Corticosteroid-free strategies in liver transplantation. Drugs. 2006;66:1853–62.

    Article  PubMed  Google Scholar 

  15. Pongratz D. Therapeutic options in autoimmune inflammatory myopathies (dermatomyositis, polymyositis, inclusion body myositis). J Neurol. 2006;253:v64–5.

    Article  PubMed  CAS  Google Scholar 

  16. Rezzani R. Exploring cyclosporine A-side effects and the protective role-played by antioxidants: the morphological and immunohistochemical studies. Histol Histopathol. 2006;21(3):301–16.

    CAS  PubMed  Google Scholar 

  17. Zhang C, Beckermann B, Kallifatidis G, Liu Z, Rittgen W, Edler L, et al. Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma. Int J Oncol. 2006;29:1295–301.

    CAS  PubMed  Google Scholar 

  18. Pujades-Rodriguez M, Smith C, Hubbard R. Inhaled corticosteroids and the risk of fracture in chronic obstructive pulmonary disease. QJM. 2007;100:509–17.

    Article  CAS  PubMed  Google Scholar 

  19. Hu X-Y, Wu R-H, Logue M, Blondel C, Lai LYW, Stuart B, et al. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: a systematic review and meta-analysis. PLoS ONE. 2017;12:e0181780.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Ban NK, Thoa NTK, Linh TM, Van Kiem P, Nhiem NX, Tai BH, et al. Labdane-type diterpenoids from Vitex limonifolia and their antivirus activities. J Nat Med. 2018;72:290–7.

    Article  CAS  PubMed  Google Scholar 

  21. Jantan I, Ahmad W, Bukhari SNA. Corrigendum: Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. Front Plant Sci. 2018;9:1178.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Che L, Zhou Q, Liu Y, Hu L, Peng X, Wu C, et al. Flaxseed oil supplementation improves intestinal function and immunity, associated with altered intestinal microbiome and fatty acid profile in pigs with intrauterine growth retardation. Food Funct. 2019;10:8149–60.

    Article  CAS  PubMed  Google Scholar 

  23. Hosseinzadeh H, Karimi G, Niapoor M. Antidepressant effect of Crocus sativus L. stigma extracts and their constituents, crocin and safranal, in mice. I International Symposium on Saffron Biology and Biotechnology 6502003. pp. 435–45.

  24. Hosseinzadeh H, Noraei NB. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice. Phytother Res. 2009;23:768–74.

    Article  CAS  PubMed  Google Scholar 

  25. Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H. The effect of chronic administration of saffron (Crocus sativus) stigma aqueous extract on systolic blood pressure in rats. Jundishapur J Nat Pharm Prod. 2013;8:175.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Korani S, Korani M, Sathyapalan T, Sahebkar A. Therapeutic effects of Crocin in autoimmune diseases: a review. BioFactors. 2019;45:835–43.

    Article  CAS  PubMed  Google Scholar 

  27. Boskabady M, Tabatabaee A, Byrami G. The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs. Phytomedicine. 2012;19:904–11.

    Article  CAS  PubMed  Google Scholar 

  28. Byrami G, Boskabady MH, Jalali S, Farkhondeh T. The effect of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite in ovalbumin sensitized Guinea-pigs. J Ethnopharmacol. 2013;147:530–5.

    Article  PubMed  Google Scholar 

  29. Vijayabhargava K, Asad M. Effect of stigmas of Crocus sativus L. (saffron) on cell mediated and humoral immunity. Nat Prod J. 2011;1:151–5.

    CAS  Google Scholar 

  30. Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei A, Alavinejad A. The effect of Crocus sativus extract on human lymphocytes’ cytokines and T helper 2/T helper 1 balance. J Med Food. 2011;14:1538–45.

    Article  CAS  PubMed  Google Scholar 

  31. Zeinali M, Zirak MR, Rezaee SA, Karimi G, Hosseinzadeh H. Immunoregulatory and anti-inflammatory properties of Crocus sativus (Saffron) and its main active constituents: a review. Iran J Basic Med Sci. 2019;22:334.

    PubMed  PubMed Central  Google Scholar 

  32. Caballero-Ortega H, Pereda-Miranda R, Abdullaev FI. HPLC quantification of major active components from 11 different saffron (Crocus sativus L.) sources. Food Chem. 2007;100:1126–31.

    Article  CAS  Google Scholar 

  33. Pham TQ, Cormier F, Farnworth E, Tong VH, Van Calsteren M-R. Antioxidant properties of crocin from Gardenia jasminoides Ellis and study of the reactions of crocin with linoleic acid and crocin with oxygen. J Agric Food Chem. 2000;48:1455–61.

    Article  CAS  PubMed  Google Scholar 

  34. Ouyang W, Ranganath SH, Weindel K, Bhattacharya D, Murphy TL, William CS, et al. Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity. 1998;9:745–55.

    Article  CAS  PubMed  Google Scholar 

  35. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100:655–69.

    Article  CAS  PubMed  Google Scholar 

  36. Chakir H, Wang H, Lefebvre DE, Webb J, Scott FW. T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3. J Immunol Methods. 2003;278:157–69.

    Article  CAS  PubMed  Google Scholar 

  37. Yong J, Chen G-Q, Huang B, Wu S. Correlation between the ratio of T-bet/GATA-3 and the levels of IL-4 and IFN-γ in patients with allergic asthma. Mol Med Rep. 2011;4:663–6.

    PubMed  Google Scholar 

  38. Saito M, Takaku F, Hayashi M, Tanaka I, Abe Y, Nagai Y, et al. A role of valency of concanavalin A and its chemically modified derivatives in lymphocyte activation. Monovalent monomeric concanavalin A derivative can stimulate lymphocyte blastoid transformation. J Biol Chem. 1983;258:7499–505.

    Article  CAS  PubMed  Google Scholar 

  39. Bakshi HA, Hakkim FL, Sam S. Molecular mechanism of crocin induced caspase mediated MCF-7 cell death: in vivo toxicity profiling and ex vivo macrophage activation. Asian Pac J Cancer Prev. 2016;17:1499–506.

    Article  PubMed  Google Scholar 

  40. Mostafavinia SE, Khorashadizadeh M, Hoshyar R. Antiproliferative and proapoptotic effects of crocin combined with hyperthermia on human breast cancer cells. DNA Cell Biol. 2016;35:340–7.

    Article  CAS  PubMed  Google Scholar 

  41. Lu P, Lin H, Gu Y, Li L, Guo H, Wang F, et al. Antitumor effects of crocin on human breast cancer cells. Int J Clin Exp Med. 2015;8:20316.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Moradzadeh M, Kalani MR, Avan A. The antileukemic effects of saffron (Crocus sativus L,) and its related molecular targets: a mini review. J Cell Biochem. 2019;120:4732–8.

    Article  CAS  PubMed  Google Scholar 

  43. Xia D. Ovarian cancer HO-8910 cell apoptosis induced by crocin in vitro. Nat Prod Commun. 2015;10:1934578X1501000208.

    CAS  Google Scholar 

  44. Aung H, Wang C, Ni M, Fishbein A, Mehendale S, Xie J, et al. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol. 2007;29:175.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. D’Alessandro AM, Mancini A, Lizzi AR, De Simone A, Marroccella CE, Gravina GL, et al. Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer. Nutr Cancer. 2013;65:930–42.

    Article  PubMed  CAS  Google Scholar 

  46. Chen S, Zhao S, Wang X, Zhang L, Jiang E, Gu Y, et al. Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells. Transl Lung Cancer Res. 2015;4:775.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Feyzi R, Boskabady MH, Tamijani SMS, Rafatpanah H, Rezaei SA. The effect of safranal on Th1/Th2 cytokine balance. Iran J Immunol. 2016;13:263–73.

    PubMed  Google Scholar 

  48. Cohn L, Homer RJ, Niu N, Bottomly K. T helper 1 cells and interferon γ regulate allergic airway inflammation and mucus production. J Exp Med. 1999;190:1309–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Rabe SZT, Iranshahi M, Mahmoudi M. In vitro anti-inflammatory and immunomodulatory properties of umbelliprenin and methyl galbanate. J Immunotoxicol. 2016;13:209–16.

    Article  CAS  Google Scholar 

  50. Kohno S, Murata T, Sugiura A, Ito C, Iranshahi M, Hikita K, et al. Methyl galbanate, a novel inhibitor of nitric oxide production in mouse macrophage RAW264. 7 cells. J Nat Med. 2011;65:353–9.

    Article  CAS  PubMed  Google Scholar 

  51. Ghiasian M, Khamisabadi F, Kheiripour N, Karami M, Haddadi R, Ghaleiha A, et al. Effects of crocin in reducing DNA damage, inflammation, and oxidative stress in multiple sclerosis patients: a double-blind, randomized, and placebo-controlled trial. J Biochem Mol Toxicol. 2019;33: e22410.

    Article  CAS  PubMed  Google Scholar 

  52. Shoda LK, Young DL, Ramanujan S, Whiting CC, Atkinson MA, Bluestone JA, et al. A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity. 2005;23:115–26.

    Article  CAS  PubMed  Google Scholar 

  53. Tisch R, McDevitt H. Insulin-dependent diabetes mellitus. Cell. 1996;85:291–7.

    Article  CAS  PubMed  Google Scholar 

  54. Atkinson MA, Gianani R. The pancreas in human type 1 diabetes: providing new answers to age-old questions. Curr Opin Endocrinol Diabetes Obes. 2009;16:279–85.

    Article  PubMed  Google Scholar 

  55. Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001;358:221–9.

    Article  CAS  PubMed  Google Scholar 

  56. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Crocin attenuate Tumor Necrosis Factor-alpha (TNF-α) and interleukin-6 (IL-6) in streptozotocin-induced diabetic rat aorta. Cytokine. 2016;88:20–8.

    Article  CAS  PubMed  Google Scholar 

  57. Liu W, Sun Y, Cheng Z, Guo Y, Liu P, Wen Y. Crocin exerts anti-inflammatory and anti-arthritic effects on type II collagen-induced arthritis in rats. Pharm Biol. 2018;56:209–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Li L, Zhang H, Jin S, Liu C. Effects of crocin on inflammatory activities in human fibroblast-like synoviocytes and collagen-induced arthritis in mice. Immunol Res. 2018;66:406–13.

    Article  PubMed  Google Scholar 

  59. Li J, Lei H-T, Cao L, Mi Y-N, Li S, Cao Y-X. Crocin alleviates coronary atherosclerosis via inhibiting lipid synthesis and inducing M2 macrophage polarization. Int Immunopharmacol. 2018;55:120–7.

    Article  CAS  PubMed  Google Scholar 

  60. Frostegård J, Ulfgren A-K, Nyberg P, Hedin U, Swedenborg J, Andersson U, et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis. 1999;145:33–43.

    Article  PubMed  Google Scholar 

  61. Senapati S, Barnhart K. Managing endometriosis associated infertility. Clin Obstet Gynecol. 2011;54:720.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kjerulff KH, Erickson BA, Langenberg PW. Chronic gynecological conditions reported by US women: findings from the National Health Interview Survey, 1984 to 1992. Am J Public Health. 1996;86:195–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Szymanowski K, Niepsuj-Biniaś J, Dera-Szymanowska A, Wołuń-Cholewa M, Yantczenko A, Florek E, et al. An influence of immunomodulation on Th1 and Th2 immune response in endometriosis in an animal model. Biomed Res Int. 2013;2013:1–7.

    Article  Google Scholar 

  64. Liu Y, Qin X, Lu X. Crocin improves endometriosis by inhibiting cell proliferation and the release of inflammatory factors. Biomed Pharmacother. 2018;106:1678–85.

    Article  CAS  PubMed  Google Scholar 

  65. Marques VP, Gonçalves GM, Feitoza CQ, Cenedeze MA, Bertocchi APF, Damião MJ, et al. Influence of TH1/TH2 switched immune response on renal ischemia-reperfusion injury. Nephron Exp Nephrol. 2006;104:e48–56.

    Article  CAS  PubMed  Google Scholar 

  66. Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm Pharm Sci. 2005;8:387–93.

    CAS  PubMed  Google Scholar 

  67. Chen Y, Qi B, Xu W, Ma B, Li L, Chen Q, et al. Clinical correlation of peripheral CD4+-cell sub-sets, their imbalance and Parkinson’s disease. Mol Med Rep. 2015;12:6105–11.

    Article  CAS  PubMed  Google Scholar 

  68. Browne TC, McQuillan K, McManus RM, O’Reilly J-A, Mills KH, Lynch MA. IFN-γ production by amyloid β–specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer’s disease. J Immunol. 2013;190:2241–51.

    Article  CAS  PubMed  Google Scholar 

  69. Kustrimovic N, Comi C, Magistrelli L, Rasini E, Legnaro M, Bombelli R, et al. Parkinson’s disease patients have a complex phenotypic and functional Th1 bias: cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naive and drug-treated patients. J Neuroinflammation. 2018;15:1–17.

    Article  CAS  Google Scholar 

  70. Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA. Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytother Res. 2012;26(3):381–6.

    Article  CAS  PubMed  Google Scholar 

  71. Mohammadzadeh L, Hosseinzadeh H, Abnous K, Razavi BM. Neuroprotective potential of crocin against malathion-induced motor deficit and neurochemical alterations in rats. Environ Sci Pollut Res Int. 2018;25:4904–14.

    Article  CAS  PubMed  Google Scholar 

  72. Heidari S, Mehri S, Hosseinzadeh H. Memory enhancement and protective effects of crocin against D-galactose aging model in the hippocampus of Wistar rats. Iran J Basic Med Sci. 2017;20:1250.

    PubMed  PubMed Central  Google Scholar 

  73. Huber J, Ramos H, Gill M, Farrar J. Type I interferon reverses human Th2 commitment and stability by repressing GATA3 (9111). Am Assoc Immnol. 2010;185(2):813–7.

    CAS  Google Scholar 

  74. Dheda K, Huggett JF, Bustin SA, Johnson MA, Rook G, Zumla A. Validation of housekeeping genes for normalizing RNA expression in real-time PCR. Biotechniques. 2004;37:112–9.

    Article  CAS  PubMed  Google Scholar 

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Funding

The authors gratefully acknowledge the Vice-Chancellor of Research in Mashhad University of Medical Sciences, Mashhad, Iran (grant number 941443) for approval and financial support of this research.

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Authors and Affiliations

  1. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Hakimeh Abdi & Zahra Aganj

  2. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Hossein Hosseinzadeh

  3. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Fatemeh Mosaffa

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  1. Hakimeh Abdi
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  2. Zahra Aganj
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  4. Fatemeh Mosaffa
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Contributions

HHZ conceived the original idea, obtained the funding, and approved the final version of the manuscript. FM designed the research proposal and interpreted data, participated in revising the article, and supervised the project. HA carried out the experiments, was involved in analysis and interpretation of results and wrote the manuscript with support from FM. ZA carried out the experiments and was involved in the analysis and interpretation of results.

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Correspondence to Hossein Hosseinzadeh or Fatemeh Mosaffa.

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Abdi, H., Aganj, Z., Hosseinzadeh, H. et al. Crocin restores the balance of Th1/Th2 immune cell response in ConA-treated human lymphocytes. Pharmacol. Rep 74, 513–522 (2022). https://doi.org/10.1007/s43440-022-00362-3

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