Skip to main content

Advertisement

Log in

Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis in rats

  • Article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Astaxanthin (ATX), a natural xanthophyll carotenoid, has shown to exert significant protective effects against various diseases via its antioxidant and anti-inflammatory properties. However, its potential role in arthritis is still not reported. Therefore, the aim of the present study was to investigate the potential anti-arthritic properties of ATX against complete Freund’s adjuvant (CFA)-induced arthritis rats.

Methods

Adjuvant arthritis was induced by single intraplantar injection of complete Freund’s adjuvant (CFA) in the left hind paw of adult female Wistar rats. ATX (25, 50 and 100 mg/kg) and indomethacin (5 mg/kg) were given orally from days 14 to 28. The anti-arthritic activity was evaluated through various nociceptive behavioral tests (mechanical allodynia, mechanical hyperalgesia, cold allodynia, and thermal hyperalgesia), paw edema assessment, and arthritis scores. Serum tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and cyclic citrullinated peptide (CCP) antibody levels were assessed. Moreover, malondialdehyde (MDA), nitrite, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were also evaluated.

Results

Oral administration of ATX (50 and 100 mg/kg) exhibited significant anti-arthritic activity via enhancing the nociceptive threshold, reducing paw edema and improving arthritis scores. Moreover, ATX treatment also markedly suppressed inflammatory and oxidative mediators in adjuvant-administered rats.

Conclusions

Our findings suggest that ATX possesses potential anti-arthritic activity, which could be attributed to its anti-inflammatory and antioxidant properties.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Lan Z, Wei M, Chen L, Xie G, Liu X, Zhang X. Role of sinomenine on complete freund’s adjuvant-induced arthritis in rats. IUBMB Life. 2016;68:429–35.

    CAS  PubMed  Google Scholar 

  2. Chang Y, Jia X, Wei F, Wang C, Sun X, Xu S, et al. CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage. Sci Rep. 2016;6:26239.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Mazzucchelli R, Fernandez EP, Crespí-Villarías N, Quirós-Donate J, Vadillo AG, Espinosa M, et al. Trends in hip fracture in patients with rheumatoid arthritis: results from the Spanish National Inpatient Registry over a 17-year period (1999–2015). TREND-AR study. RMD Open. 2018;4:e000671.

    PubMed  PubMed Central  Google Scholar 

  4. Umar S, Sarwar AHMG, Umar K, Ahmad N, Sajad M, Ahmad S, et al. Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis. Cell Immunol. 2013;284:51–9.

    CAS  PubMed  Google Scholar 

  5. Veselinovic M, Barudzic N, Vuletic M, Zivkovic V, Tomic-Lucic A, Djuric D, et al. Oxidative stress in rheumatoid arthritis patients: relationship to diseases activity. Mol Cell Biochem. 2014;391:225–32.

    CAS  PubMed  Google Scholar 

  6. Quiñonez-Flores CM, González-Chávez SA, Del Río Nájera D, Pacheco-Tena C. Oxidative stress relevance in the pathogenesis of the rheumatoid arthritis: a systematic review. BioMed Res Int. 2016;13(Supplement):1–14.

    Google Scholar 

  7. Fang Q, Guo S, Zhou H, Han R, Wu P, Han C. Astaxanthin protects against early burn-wound progression in rats by attenuating oxidative stress-induced inflammation and mitochondria-related apoptosis. Sci Rep. 2017;7:41440.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Yeh P-T, Huang H-W, Yang C-M, Yang W-S, Yang C-H. Astaxanthin inhibits expression of retinal oxidative stress and inflammatory mediators in streptozotocin-induced diabetic rats. PLoS One. 2016;11:e0146438.

    PubMed  PubMed Central  Google Scholar 

  9. Yamagishi R, Aihara M. Neuroprotective effect of astaxanthin against rat retinal ganglion cell death under various stresses that induce apoptosis and necrosis. Mol Vis. 2014;20:1796–805.

    PubMed  PubMed Central  Google Scholar 

  10. Xue X-L, Han X-D, Li Y, Chu X-F, Miao W-M, Zhang J-L, et al. Astaxanthin attenuates total body irradiation-induced hematopoietic system injury in mice via inhibition of oxidative stress and apoptosis. Stem Cell Res Ther. 2017;8:7.

    PubMed  PubMed Central  Google Scholar 

  11. Farruggia C, Kim M-B, Bae M, Lee Y, Pham TX, Yang Y, et al. Astaxanthin exerts anti-inflammatory and antioxidant effects in macrophages in NRF2-dependent and independent manners. J Nutr Biochem. 2018;62:202–9.

    CAS  PubMed  Google Scholar 

  12. Lee S, Bai S, Lee K, Namkoong S, Na H, Ha K, et al. Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I(kappa)B kinase-dependent NF-kappaB activation. Mol Cells. 2003;16:97–105.

    CAS  PubMed  Google Scholar 

  13. Ito N, Saito H, Seki S, Ueda F, Asada T. Effects of composite supplement containing astaxanthin and sesamin on cognitive functions in people with mild cognitive impairment: a randomized, double-blind, placebo-controlled trial. J Alzheimer’s Dis. 2018;62:1767–75.

    CAS  Google Scholar 

  14. Mashhadi NS, Zakerkish M, Mohammadiasl J, Zarei M, Mohammadshahi M, Haghighizadeh MH. Astaxanthin improves glucose metabolism and reduces blood pressure in patients with type 2 diabetes mellitus. Asia Pac J Clin Nutr. 2018;27:341–6.

    CAS  PubMed  Google Scholar 

  15. Imai A, Oda Y, Ito N, Seki S, Nakagawa K, Miyazawa T, et al. Effects of dietary supplementation of astaxanthin and sesamin on daily fatigue: a randomized, double-blind, placebo-controlled, two-way crossover study. Nutrients. 2018;10:281.

    PubMed Central  Google Scholar 

  16. Kupcinskas L, Lafolie P, Lignell Å, Kiudelis G, Jonaitis L, Adamonis K, et al. Efficacy of the natural antioxidant astaxanthin in the treatment of functional dyspepsia in patients with or without Helicobacter pylori infection: a prospective, randomized, double blind, and placebo-controlled study. Phytomedicine. 2008;15:391–9.

    CAS  PubMed  Google Scholar 

  17. Barrios V, Escobar C, Cicero AFG, Burke D, Fasching P, Banach M, et al. A nutraceutical approach (Armolipid Plus) to reduce total and LDL cholesterol in individuals with mild to moderate dyslipidemia: review of the clinical evidence. Atheroscler Suppl. 2017;24:1–15.

    PubMed  Google Scholar 

  18. Group CS. Carotenoids in age-related maculopathy Italian study (CARMIS): two-year results of a randomized study. Eur J Ophthalmol. 2012;22:216–25.

    Google Scholar 

  19. Arora R, Kuhad A, Kaur I, Chopra K. Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats. Eur J Pain. 2015;19:940–52.

    CAS  PubMed  Google Scholar 

  20. Preuss HG, Echard B, Yamashita E, Perricone NV. High dose astaxanthin lowers blood pressure and increases insulin sensitivity in rats: are these effects interdependent? Int J Med Sci. 2011;8:126–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ali EA, Barakat BM, Hassan R. Antioxidant and angiostatic effect of Spirulina Platensis suspension in complete Freund’s adjuvant-induced arthritis in rats. PLoS One. 2015;10:e0121523.

    PubMed  PubMed Central  Google Scholar 

  22. Kuhad A, Chopra K. Tocotrienol attenuates oxidative–nitrosative stress and inflammatory cascade in experimental model of diabetic neuropathy. Neuropharmacology. 2009;57:456–62.

    CAS  PubMed  Google Scholar 

  23. Mittal R, Kumar A, Singh DP, Bishnoi M, Nag TC. Ameliorative potential of rutin in combination with nimesulide in STZ model of diabetic neuropathy: targeting Nrf2/HO-1/NF-kB and COX signalling pathway. Inflammopharmacology. 2018;26:755–68.

    CAS  PubMed  Google Scholar 

  24. Marwaha L, Bansal Y, Singh R, Saroj P, Sodhi RK, Kuhad A. Niflumic acid, a TRPV1 channel modulator, ameliorates stavudine-induced neuropathic pain. Inflammopharmacology. 2016;24:319–34.

    CAS  PubMed  Google Scholar 

  25. Taksande BG, Gawande DY, Chopde CT, Umekar MJ, Kotagale NR. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats. Biomed Pharmacother. 2017;86:271–8.

    CAS  PubMed  Google Scholar 

  26. Wills E. Mechanisms of lipid peroxide formation in animal tissues. Biochem J. 1966;99:667–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Anal Biochem. 1982;126:131–8.

    CAS  PubMed  Google Scholar 

  28. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82:70–7.

    CAS  PubMed  Google Scholar 

  29. Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys. 1978;186:189–95.

    CAS  PubMed  Google Scholar 

  30. Bansal Y, Singh R, Saroj P, Sodhi RK, Kuhad A. Naringenin protects against oxido-inflammatory aberrations and altered tryptophan metabolism in olfactory bulbectomized-mice model of depression. Toxicol Appl Pharmacol. 2018;355:257–68.

    CAS  PubMed  Google Scholar 

  31. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–75.

    CAS  PubMed  Google Scholar 

  32. Jiang X, Yan Q, Liu F, Jing C, Ding L, Zhang L, et al. Chronic trans-astaxanthin treatment exerts antihyperalgesic effect and corrects co-morbid depressive like behaviors in mice with chronic pain. Neurosci Lett. 2018;662:36–43.

    CAS  PubMed  Google Scholar 

  33. Sharma K, Sharma D, Sharma M, Sharma N, Bidve P, Prajapati N, et al. Astaxanthin ameliorates behavioral and biochemical alterations in in vitro and in vivo model of neuropathic pain. Neurosci Lett. 2018;674:162–70.

    CAS  PubMed  Google Scholar 

  34. Datta S, Kundu S, Ghosh P, De S, Ghosh A, Chatterjee M. Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis. Clin Rheumatol. 2014;33:1557–64.

    PubMed  Google Scholar 

  35. Kim EY, Moudgil KD. Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines. Cytokine. 2017;98:87–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen Z, Bozec A, Ramming A, Schett G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat Rev Rheumatol. 2018;15:9–17.

    Google Scholar 

  37. Altomonte L, Zoli A, Mirone L, Scolieri P, Magaro M. Serum levels of interleukin-1b, tumour necrosis factor-a and interleukin-2 in rheumatoid arthritis. Correlation with disease activity. Clin Rheumatol. 1992;11:202–5.

    CAS  PubMed  Google Scholar 

  38. Tetta C, Camussi G, Modena V, Di Vittorio C, Baglioni C. Tumour necrosis factor in serum and synovial fluid of patients with active and severe rheumatoid arthritis. Ann Rheum Dis. 1990;49:665–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Brzustewicz E, Bryl E. The role of cytokines in the pathogenesis of rheumatoid arthritis–Practical and potential application of cytokines as biomarkers and targets of personalized therapy. Cytokine. 2015;76:527–36.

    CAS  PubMed  Google Scholar 

  40. Mateen S, Moin S, Shahzad S, Khan AQ. Level of inflammatory cytokines in rheumatoid arthritis patients: correlation with 25-hydroxy vitamin D and reactive oxygen species. PLoS ONE. 2017;12:e0178879.

    PubMed  PubMed Central  Google Scholar 

  41. Feng Y, Chu A, Luo Q, Wu M, Shi X, Chen Y. The protective effect of astaxanthin on cognitive function via inhibition of oxidative stress and inflammation in the brains of chronic T2DM rats. Front Pharmacol. 2018;9:748.

    PubMed  PubMed Central  Google Scholar 

  42. Park DR, Ko R, Kwon SH, Min B, Yun SH, Kim MH, et al. FlexPro MD, a Mixture of Krill Oil, Astaxanthin, and Hyaluronic Acid, Suppresses Lipopolysaccharide-Induced Inflammatory Cytokine Production Through Inhibition of NF-κB. J Med Food. 2016;19:1196–203.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Altindag O, Karakoc M, Kocyigit A, Celik H, Soran N. Increased DNA damage and oxidative stress in patients with rheumatoid arthritis. Clin Biochem. 2007;40:167–71.

    CAS  PubMed  Google Scholar 

  44. Mateen S, Moin S, Khan AQ, Zafar A, Fatima N. Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis. PLoS ONE. 2016;11:e0152925.

    PubMed  PubMed Central  Google Scholar 

  45. Phull A-R, Nasir B, ul Haq I, Kim SJ. Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid arthritis. Chem Biol Interact. 2018;281:121–36.

    CAS  PubMed  Google Scholar 

  46. Bi J, Cui R, Li Z, Liu C, Zhang J. Astaxanthin alleviated acute lung injury by inhibiting oxidative/nitrative stress and the inflammatory response in mice. Biomed Pharmacother. 2017;95:974–82.

    CAS  PubMed  Google Scholar 

  47. Park JS, Chyun JH, Kim YK, Line LL, Chew BP. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab. 2010;7:18.

    Google Scholar 

  48. Zhu X, Chen Y, Chen Q, Yang H, Xie X. Astaxanthin promotes Nrf2/ARE signaling to alleviate renal fibronectin and collagen IV accumulation in diabetic rats. J Diabetes Res. 2018;18:1–7.

    CAS  Google Scholar 

  49. Niu T, Xuan R, Jiang L, Wu W, Zhen Z, Song Y, et al. Astaxanthin induces the Nrf2/HO-1 antioxidant pathway in human umbilical vein endothelial cells by generating trace amounts of ROS. J Agric Food Chem. 2018;66:1551–9.

    CAS  PubMed  Google Scholar 

  50. Mallya R, Berry H, Hamilton E, Mace B, Pepys M. Correlation of clinical parameters of disease activity in rheumatoid arthritis with serum concentration of C-reactive protein and erythrocyte sedimentation rate. J Rheumatol. 1982;9:224–8.

    CAS  PubMed  Google Scholar 

  51. Matsuno H, Yudoh K, Nakazawa F, Koizumi F. Relationship between histological findings and clinical findings in rheumatoid arthritis. Pathol Int. 2002;52:527–33.

    PubMed  Google Scholar 

  52. Plant MJ, Williams AL, O’Sullivan MM, Lewis PA, Coles EC, Jessop JD. Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis. Arthritis Rheum. 2000;43:1473–7.

    CAS  PubMed  Google Scholar 

  53. Kim K-W, Kim B-M, Moon H-W, Lee S-H, Kim H-R. Role of C-reactive protein in osteoclastogenesis in rheumatoid arthritis. Arthritis Res Ther. 2015;17:41.

    PubMed  PubMed Central  Google Scholar 

  54. Rhodes B, Fürnrohr BG, Vyse TJ. C-reactive protein in rheumatology: biology and genetics. Nat Rev Rheumatol. 2011;7:282–9.

    CAS  PubMed  Google Scholar 

  55. Vossenaar ER, van Venrooij WJ. Anti-CCP antibodies, a highly specific marker for (early) rheumatoid arthritis. Clin Appl Immunol Rev. 2004;4:239–62.

    CAS  Google Scholar 

  56. Xu J, Gao H, Zhang L, Chen C, Yang W, Deng Q, et al. A combination of flaxseed oil and astaxanthin alleviates atherosclerosis risk factors in high fat diet fed rats. Lipids Health Dis. 2014;13:63.

    PubMed  PubMed Central  Google Scholar 

  57. Li Y, Kakkar R, Wang J. In vivo and in vitro approach to anti-arthritic and anti-inflammatory effect of crocetin by alteration of nuclear factor-E2-related factor 2/hem oxygenase (HO)-1 and NF-κB expression. Front Pharmacol. 2018;9:1341.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Ambati R, Phang S-M, Ravi S, Aswathanarayana R. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications—a review. Mar Drugs. 2014;12:128–52.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

All the authors acknowledge the funding provided by the University Grants Commission (UGC), New Delhi, India. Grant Number is F.38-11/2016/(SA-III).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kanwaljit Chopra.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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

Kumar, A., Dhaliwal, N., Dhaliwal, J. et al. Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis in rats. Pharmacol. Rep 72, 104–114 (2020). https://doi.org/10.1007/s43440-019-00022-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43440-019-00022-z

Keywords

Navigation