Skip to main content
SpringerLink
Log in

Dietary amaranths modulate the immune response via balancing Th1/Th2 and Th17/Treg response in collagen-induced arthritis

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Imbalance between Th1/Th2 and Th17/Treg is crucial in RA progression. Various dietary factors can modulate the disease severity by restoring the balance in differentiation of CD4+ T cell subsets. Dietary amaranths hold an important part of diet as vegetables, where commonly consumed species includes Amaranthus cruentus (Ac), Amaranthus viridis (Av), and Amaranthus hybridus (Ah). The present study focuses on to evaluate whether these dietary amaranths can modulate the immune activation in collagen-induced arthritis. For in vivo study, Female Wistar rats were immunized with type II collagen and after immunization period, rats were separately supplemented with cooked Ac, Av, and Ah at 500 mg/100 g bwt concentration mixed with standard rat feed for 60 days. HPTLC fingerprint analysis identified peaks for compounds in these three amaranths. The results showed a protective role of immunomodulation in Th1/Th2 response of the three dietary amaranths, by significantly augmenting lymphocyte activation with increased IL-4 secretion, but decreased IFN-γ by cultured spleen lymphocytes subjected to collagen-induced inflammation. Moreover, Th17/Treg imbalance created by increase in IL-17 and decrease in IL-10 was significantly balanced by the three dietary supplemented groups. Furthermore, Th1/Th2 status reflected from Tbet/GATA3 ratio and Th17/Treg status reflected from RORγt/FOXP3 ratio was significantly decreased in the three dietary amaranth supplemented groups. Thus, dietary amaranths provide an immune-modulating role by keeping the balance between Th1/Th2 and Th17/Treg response in collagen-induced inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

Th1:

T helper 1 cell

Th2:

T helper 2 cell

Th17:

T helper 17 cell

Treg:

T regulatory cell

Tbet:

T box transcription factor

GATA3:

GATA3 binding protein

FOXP3:

Forkhead box P3

RORγt:

Retinoic acid related orphan receptor γt

Con A:

Concanavalin A

References

  1. Blunden G, Yang M, Janicsak MI, Carbot-Cuervo A (1999) Betaine distribution in the Amaranthaceae. Biochem Syst Ecol 27:87–92

    Article  CAS  Google Scholar 

  2. Tyszka-Czochara M, Pasko P, Zagrodzki P, Gajdzik E, Wietecha-Posluszny R, Gorinstein S (2016) Selenium supplementation of amaranth sprouts influences betacyanin content and improves anti-inflammatory properties via NFκB in murine RAW 264.7 macrophages. Biol Trace Elem Res 169:320–330. https://doi.org/10.1007/s12011-015-0429-x

    Article  CAS  PubMed  Google Scholar 

  3. Gandhi P, Khan Z, Niraj K (2011) In vitro assay of anti-proliferative potential of Amaranthus cruentus aqueous extract on human peripheral blood lymphocytes. Curr Trends Biotechnol Chem Res 1:42–48

    Google Scholar 

  4. Larbie C, Appiah-Opong R, Acheampong F, Tuffour I, Uto T, Torkornoo D et al (2015) Anti-proliferative effect of Amaranthus viridis linn. On human leukemic cell lines: a preliminary study. Int J Biol Pharma Res 6:236

    Google Scholar 

  5. Adewale A, Olorunju AE (2013) Modulatory of effect of fresh Amaranthus caudatus and Amaranthus hybridus aqueous leaf extracts on detoxify enzymes and micronuclei formation after exposure to sodium arsenite. Pharmacognosy Res 5:300–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gaafar T, Farid R, Raafat H, Bayoumi F, Gerges B (2015) The TH17/Treg imbalance in rheumatoid arthritis and relation to disease activity. J Clin Cell Immunol 6:381

    Article  Google Scholar 

  7. Boissier MC, Assier E, Falgarone G, Bessis N (2008) Shifting the imbalance from Th1/Th2 to Th17/treg: the changing rheumatoid arthritis paradigm. Joint Bone Spine 75:373–375

    Article  CAS  PubMed  Google Scholar 

  8. Jäger A, Kuchroo VK (2010) Effector and regulatory T cell subsets in autoimmunity and tissue inflammation. Scand J Immunol 72(3):173–184

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wan YY, Flavell RA (2008) TGF-beta and regulatory T cell in immunity and autoimmunity. J Clin Immunol 28:647–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Boniface K, Moynet D, Mossalayi MD (2013) Role of Th17 cells in the pathogenesis of rheumatoid arthritis. World J Rheumatol 3(3):25–31

    Article  Google Scholar 

  11. Mateen S, Zafar A, Moin S, Khan AQ, Zubair S (2016) Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clin Chim Acta 455:161–171

    Article  CAS  PubMed  Google Scholar 

  12. El-Gamal YM, Elmasry OA, El-Ghoneimy DH, Islam M (2011) Immunomodulatory effects of food. Egypt J Pediatr Allergy Immunol 9(1):3–13

    Google Scholar 

  13. Paul V, Verma S, Sushma PA (2012) Effect of cooking and processing methods on oxalate content of green leafy vegetables and pulses. Asian J. Food Agro-Ind 5:311–314

    Google Scholar 

  14. Brand DD, Rosloniec LKA (2007) Collagen induced arthritis. Nat Protoc 2:1269–1275

    Article  CAS  PubMed  Google Scholar 

  15. Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Britti D, Maio MD, Caputi AP (2001) Absence of endogeneous interleukin-10 enhances the evolution of murine type II Collagen-Induced Arthritis. Eur Cytokine Netw 12(4):568–580

    CAS  PubMed  Google Scholar 

  16. Wang J, Zhang Q, Jin S, He D, Zhao S, Liu S (2008) Genistein modulate immune responses in collagen-induced rheumatoid arthritis model. Maturitas 59:405–412

    Article  CAS  PubMed  Google Scholar 

  17. Peter J, Aswathy IS, Sabu V, Krishnan S, Helen A (2018) Ameliorative efficacy of dietary amaranth species on JAK/STAT signaling in collagen induced arthritis. Indian J Sci Res 20(1):12–19

    CAS  Google Scholar 

  18. Cope AP, Schulze-Koops H, Aringer M (2007) The central role of T cells in rheumatoid arthritis. Clin Exp Rheumatol Clin Exp Rheumatol 25(46):S4–S11

    CAS  PubMed  Google Scholar 

  19. Niu Q, Cai B, Huang ZC, Shi YY, Wang LL (2012) Disturbed Th17/Treg balance in patient with rheumatoid arthritis. Rheumatol Int 32:2731–2736

    Article  CAS  PubMed  Google Scholar 

  20. Kennedy A, Schmidt EM, Cribbs AP, Penn H, Amjadi P, Syed K (2014) A novel upstream enhancer of FOXP3, sensitive to methylation-induced silencing, exhibits dysregulated methylation in rheumatoid arthritis Treg cells. Eur J Immunol 44:2968–2978

    Article  CAS  PubMed  Google Scholar 

  21. Kaminogawa S, Nanno M (2004) Modulation of immune functions by foods. eCAM 1(3):241–250

    PubMed  Google Scholar 

  22. Suffo AKL, Ashish R, Tedonkeng PE, Kuiate JR (2016) Effect of processing methods on chemical composition and antioxidant activities of two Amaranthus sp. harvested in west region of cameroons. J Nutr Food Sci 6:477

    Google Scholar 

  23. Silvaa RO, Sousaa FBM, Damascenoa SRB, Carvalhoa NS, Silvaa VG, Oliveirab FRMA, Sousac DP, Aragãod KS, Barbosaa ALR, Freitasb RM, Medeiros JVR (2014) Phytol, a diterpene alcohol, inhibits the inflammatory response by reducing cytokine production and oxidative stress. Fundam Clin Pharmacol. https://doi.org/10.1111/fcp.12049

    Article  Google Scholar 

  24. Salvamani S, Gunasekaran B, Shukor MY, Abu Bakar MZ, Ahmad SA (2016) Phytochemical investigation, hypocholesterolemic and anti-atherosclerotic effects of Amaranthus viridis leaf extract in hypercholesterolemia-induced rabbits. RSC Adv 6:32685–32696

    Article  CAS  Google Scholar 

  25. Kumari S, Elancheran R, Devi R (2018) Phytochemical screening, antioxidant, antityrosinase, and antigenotoxic potential of Amaranthus viridis extract. Indian J Pharmacol 50:130–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Peter K, Gandhi P (2017) Rediscovering the therapeutic potential of Amaranthus species: a review. Egypt J Basic Appl Sci 4:196–205

    Article  Google Scholar 

Download references

Funding

This study was financially supported by Kerala State Council for Science Technology and Environment (KSCSTE), Thiruvananthapuram, Kerala, India (No. 001/FSHP/12/CSTE).

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthapuram, Kerala, 695581, India

    Jasmine Peter, Vidya Sabu, I. S. Aswathy, Santhi Krishnan, S. S. Lal Preethi, Monisha Simon & A. Helen

Authors
  1. Jasmine Peter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vidya Sabu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. S. Aswathy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Santhi Krishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. S. Lal Preethi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monisha Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Helen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JP, VS and HA designed, performed, analyzed the data and wrote the manuscript. AIS and SK contributed significantly to the analysis of the study. LSS and MS contribute to the manuscript preparation.

Corresponding author

Correspondence to A. Helen.

Ethics declarations

Conflicts of interest

The authors declare that there is no conflict of interest.

Ethical approval

The animal use protocol was reviewed and approved by Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) (Registration Number 218/CPCSEA) IAEC-KU-6/2014-15-BC-AH (27) according to the Government of India accepted principles for laboratory animal use and care.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peter, J., Sabu, V., Aswathy, I.S. et al. Dietary amaranths modulate the immune response via balancing Th1/Th2 and Th17/Treg response in collagen-induced arthritis. Mol Cell Biochem 472, 57–66 (2020). https://doi.org/10.1007/s11010-020-03783-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-020-03783-x

Keywords

Search

Navigation