Cymbopogon citratus mitigates neurobehavioral impairments via inhibition of oxidative stress and inflammatory changes in mice submitted to complete Freund adjuvant



Cymbopogon citratus aqueous leaf extract (CYC) otherwise known as lemongrass tea is used for achy joints (rheumatism) and central nervous system disorders in ethnomedicine. This study was designed to investigate the effects of CYC on neurobehavioral, oxidative, and inflammatory changes produced by complete Freund adjuvant (CFA) in male Swiss mice.


The mice were allotted into 6 groups (n = 6). The animals in group 1 received saline (control), group 2 also had saline (CFA-control), groups 3–5 received CYC (50, 100, or 200 mg/kg), whereas group 6 were given celecoxib (20 mg/kg) orally for 14 consecutive days. Mice in groups 2–6 also received 0.1 mL injection of CFA (10 mg/mL) into the left hind paw 30 min earlier on day 1. The paw volumes were measured on days 0, 7, and 14. Neurobehavioral changes were evaluated on day 14. Thereafter, the left hind paw tissues were processed for estimation of malondialdehyde, nitrite, glutathione, tumor necrosis factor-alpha, and interleukin-6 contents.


The increase in paw volume and weight produced by CFA was reduced by CYC (p < 0.05). CYC attenuated postural instability, anxiety, depression, memory deficits, and nociceptive responses in CFA-mice. The CFA-induced increases in malondialdehyde and pro-inflammatory cytokines accompanied by decreased glutathione contents in mouse hind paw were attenuated by CYC (p < 0.05).


The findings that CYC reduces inflammatory edema, neurological deficits, nociception, biomarkers of oxidative stress, and release of inflammatory cytokines in CFA-treated mice further supports its acclaimed benefit in arthritic pain in ethnomedicine.

This is a preview of subscription content, access via your institution.

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

Data availability

Data set supporting the findings and conclusion of this article is included as tables and figures attached to the main manuscript.



Rheumatoid arthritis


Complete Freund adjuvant


Tumor necrosis factor-alpha





C. citratus :

Cymbopogon citratus


Central nervous system


Ellman reagent [5′,5′-Dithiobis- (2-nitrobenzoate)]


Thiobarbituric acid


Trichloroacetic acid


Walk beam test


Tail suspension test






  1. 1.

    McCoy JM, Wicks JR, Audoly LP. The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis. J Clin Invest. 2002;110:651–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    García-González A, Gaxiola-Robles R, Zenteno-Savín T. Oxidative stress in patients with rheumatoid arthritis. Rev Investig Clin. 2015;67:46–53.

    Google Scholar 

  3. 3.

    Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum Dis Clin N Am. 2001;27:269–81.

    CAS  Article  Google Scholar 

  4. 4.

    Vant LH, Verdurmen J, Ten MH, van Dorsselaer S, Beekman A, de Graaf R. The association between arthritis and psychiatric disorders; results from a longitudinal population-based study. J Psychosom Res. 2010;68:187–93.

    Article  Google Scholar 

  5. 5.

    Devi PR, Kumari SK, Kokilavani C. Effect of vitex negundo leaf extract on the free radicals scavengers in complete Freund’s adjuvant induced arthritic rats. IJCB. 2007;22:143–7.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Wruck CJ, Fragoulis A, Gurzynski A, Brandenburg LO, Kan YW, Chan K, et al. Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice. Ann Rheum Dis. 2011;70:844–50.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Filippin L, Vercelino IR, Marroni NP, Xavier RM. Redox signalling and the inflammatory response in rheumatoid arthritis. Clin Exp Immunol. 2008;152:415–22.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Kargutkar S, Brijesh S. Anti-rheumatic activity of ananas comosus fruit peel extractin a complete freund’s adjuvant rat model. Pharm Biol. 2016;54:2616–22.

    PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Pearson CM, Wood FD. Studies of polyarthritis and other lesions induced in ratsby injection of mycobacterial adjuvant. General clinical and pathological characteristics and some modifying factors. Arthritis Rheum. 1959;2:440–59.

    Article  Google Scholar 

  10. 10.

    Omorogbe O, Ajayi AM, Ben-Azu B, Oghwere EE, Adebesin A, Aderibigbe AO, et al. Jobelyn® attenuates inflammatory responses and neurobehavioural deficits associated with complete Freund-adjuvant-induced arthritis in mice. Biomed Pharmacother. 2018;98:585–93.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Sizova L. Approaches to the treatment of early rheumatoid arthritis with disease modifying antirheumatic drugs. Br J Clin Pharmacol. 2008;66:173–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Yudoh K, Karasawa R, Masuko K, Kato T. Water-soluble fullerene (C60) inhibitsthe development of arthritis in the rat model of arthritis. Int J Nanomedicine. 2009;4:217–25.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Frech TM, Clegg DO. The utility of nutraceuticals in the treatment of osteoarthritis. Curr Rheumatol Rep. 2007;9:25–30.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  14. 14.

    Figueirinha A, Paranhos A, Perez-Alonso J, Santos-buelga C, Batista M. Cymbopogon citratus leaves: characterisation of flavonoids by HPLC-PDA-ESI/MS/MS and anapproach to their potential as a source of bioactive polyphenols. Food Chem. 2008;110:718–28.

    CAS  Article  Google Scholar 

  15. 15.

    Asaolu MF, Oyeyemi OA, Olanlokun JO. Chemical compositions, phytochemical constituents and in vitro biological activity of various extracts of Cymbopogon citratus. Pak J Nutr. 2009;8:1920–2.

    CAS  Article  Google Scholar 

  16. 16.

    Gupta PK, Rithu BS, Shruthi A, Lokur AV, Raksha M. Phytochemical screening and qualitative analysis of Cymbopogon citratus. J Pharmacogn Phytochem. 2019;8(4):3338–43.

    Google Scholar 

  17. 17.

    Quintans-Júnior LJ, Guimarães AG, Santana MT, Araújo BES, Moreira FV, Bonjardim LR, et al. Citral reduces nociceptive and inflammatory response in rodents. Braz J Pharm. 2011;21:497–502.

    Article  CAS  Google Scholar 

  18. 18.

    Carlini E, Contar DD, Silva-Filho AR, da Silveira-Filho NG, Frochtengarten ML, Bueno OF. Pharmacology of lemongrass (Cymbopogon citratus Stapf). I. Effects of teas prepared from the leaves on laboratory animals. J Ethnopharmacol. 1986;17:37–64.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  19. 19.

    Carbajal D, Casaco A, Arruzazabala L, Gonzalez R, Tolon Z. Pharmacological study of Cymbopogon citratus leaves. J Ethnopharmacol. 1989;25:103–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Blanco MM, Costa A, Freire AO, Santos JG Jr, Costa M. Neurobehavioral effect of essential oil of Cymbopogon citratus in mice. Phytomedicine. 2009;16:265–70.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Leite JR, Seabra ML, Maluf E, Assolant K, Suchecki D, Tufik S, et al. Pharmacology of lemongrass (Cymbopogon citratus Stapf). III. Assessment of eventual toxic, hypnotic and anxiolytic effects on humans. J Ethnopharmacol. 1986;17:75–83.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Yang Z, Xi J, Li J, Qu W. Biphasic effect of citral, a flavoring and scenting agent, on spatial learning and memory in rats. Pharmacol Biochem Behav. 2009;93:391–6.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Umukoro S, Adeyinka HA, Ben-Azu B, Ajayi MA. Lemon grass tea enhances memory function and attenuates scopolamine-induced amnesia in mice via inhibition of oxidative stress and acetyl-cholinesterase activity. Int J Geogr Inf Syst. 2018;24:1–14.

    Google Scholar 

  24. 24.

    Sforcin JM, Amaral JT, Femandes A, Sousa JPB, Bastos JK. Lemongrass effects on IL-1 and IL-6 production by macrophages. Nat Prod Res. 2009;23:1151–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  25. 25.

    Figueirinha A, Cruz MT, Francisco V, Lopes MC, Batista MT. Anti-inflammatory activity of Cymbopogon citratus leaf infusion in lipopolysaccharide-stimulated dendritic cells: contribution of the polyphenols. J Med Food. 2010;13:681–90.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Umukoro S, Ogboh ST, Omorogbe O, Adekeye AA, Olatunde MO. Evidence for the involvement of monoaminergic pathways in the antidepressant-like activity of Cymbopogon citratus in mice. Drug Res. 2017;67:1–6.

    Article  Google Scholar 

  27. 27.

    Hilber. An unsteady platform test for measuring static equilibrium in mice. J Neurosci Methods. 1999;88:201–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Bourin M, Hascoet M. The mouse light/dark box test. Eur J Pharmacol. 2003;463:55–65.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  29. 29.

    Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method forscreening antidepressants in mice. Psychopharmacology. 1985;85:367–70.

    CAS  Article  Google Scholar 

  30. 30.

    Casadesus G, Webber KM, Atwood CS, Pappolla MA, Perry G, Bowen RL, et al. Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice. Biochim Biophys Acta. 1762;2006:447–52.

    Google Scholar 

  31. 31.

    Bianchi C, Franceschini J. Experimental observation on Haffner’s method for testing analgesic drugs. Br J Pharmacol. 1954;9:280–4.

    CAS  Google Scholar 

  32. 32.

    Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582:6778.

    Google Scholar 

  33. 33.

    Okhawa H, Ohishi N, Yagi E. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351–8.

    Article  Google Scholar 

  34. 34.

    Green LC, Tannenbaum SR, Goldman P. Nitrate synthesisin the germ free and conventional rat. Science. 1981;212:56–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Newbould BB. Chemotherapy of arthritis induced in rats by mycobaterial adjuvant. Br J Pharmacol Chemother. 1963;21:127–36.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Zhanli X, Dai J, Yang A, Wu Y. A role for bradykinin in the development of anti-collagen antibody-induced arthritis. Rheumatology (Oxford). 2014;53:1301–6.

    Article  CAS  Google Scholar 

  37. 37.

    Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MNM. The crucial roles of inflammatory mediators in inflammation: a review. Vet World 2018; 11: 627–635.

  38. 38.

    Viana GS, Vale TG, Pinho RS, Matos FJ. Antinociceptive effect of the essential oil from Cymbopogon citratus in mice. J Ethnopharmacol. 2000;70:323–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  39. 39.

    Lorenzetti BB, Souza GE, Sarti SJ, Santos FD, Ferreira SH. Myrcene mimics the peripheral analgesic activity of lemongrass tea. J Ethnopharmacol. 1991;34:43–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Meenapriya M, Priya J. Effect of lemongrass oil on rheumatoid arthritis. Pharm Sci Res. 2017;9:237–9.

    Google Scholar 

  41. 41.

    Bartolini M, Candela M, Brugni M, Catena L, Mari F, Pomponio G, et al. Are behaviour and motor performances of rheumatoid arthritis patients influenced by subclinical cognitive impairments? A clinical and neuroimaging study. Clin Exp Rheumatol. 2002;20:491–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Geenen R, Newman S, Bossema ER, Vriezekolk JE, Boelen PA. Psychological interventions for patients with rheumatic diseases and anxiety or depression. Best Pract Res Clin Rheumatol. 2012;26:305–19.

    PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Millecamps M, Jourdan D, Leger S, Etienne M, Eschalier A, Ardid D. Circadian pattern of spontaneous behavior in monarthritic rats: a novel global approach to evaluation of chronic pain and treatment effectiveness. Arthritis Rheum. 2005;52:3470–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  44. 44.

    Shin SOY, Katz P, Wallhagen M, Julia L. Cognitive impairment in persons with rheumatoid arthritis. Arthritis Care Res. 2012;64:1144–50.

    Article  Google Scholar 

  45. 45.

    Appenzeller S, Bertolo MB, Costallat LT. Cognitive impairment in rheumatoid arthritis. Methods Find Exp Clin Pharmacol. 2004;26:339–43.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Valentin AP, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinergic anti-inflammatory pathway: a missing link in Neuroimmunomodulation. Mol Med. 2003;9:125–34.

    Article  Google Scholar 

  47. 47.

    Martelli D, McKinley MJ, McAllen RM. The cholinergic anti-inflammatory pathway: a critical review. Auton Neurosci. 2014;182:65–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    Bohanec GP, Logar D, Tomsic M, Rozman B, Dolzan V. Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients. Dis Markers. 2009;26:41–8.

    Article  Google Scholar 

  49. 49.

    Kunsch C, Sikorski JA, Sundell CL. Oxidative stress and the use of antioxidants for the treatment of rheumatoid arthritis. Curr Med Chem Immunol Endocr Metab Agents. 2005;5:249–58.

    CAS  Article  Google Scholar 

  50. 50.

    Nourmohammadi I, Athari-Nikazm S, Vafa MR, Bidari A, Jazayeri S, Hoshyarrad A, et al. Effects of antioxidant supplementations on oxidative stress in rheumatoid arthritis patients. J Biol Sci. 2010;10:63–6.

    CAS  Article  Google Scholar 

  51. 51.

    Fandohan P, Gnonlonfn B, Laleye A, Gbenou JD, Darboux R, Moudachirou M. Toxicity and gastric tolerance of essential oils from Cymbopogon citratus, Ocimum gratissimum and Ocimum basilicum in Wistar rats. Food Chem Toxicol. 2008;46:2493–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

Download references


Authors thank the technical staff of the Department of Pharmacology and Therapeutics, University of Ibadan for their assistance.

Author information




This study was carried out in collaboration with all authors. SU and BBA designed the work; AMA, BBA, AA and MA carried out the lab work; AMA and BBA did the statistical analyses; and SU, AA, and BBA wrote the first and final drafts of the manuscripts.

Corresponding author

Correspondence to Benneth Ben-Azu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval and consent to participate

The experimental procedures were performed in accordance with the NIH Ethical Guidelines for the Care and Use of Laboratory Animals (Publication No. 85-23, revised 1985) as well as the University of Ibadan’s Ethics on the Use and Care of Laboratory Animals guidelines (UI/ACUREC 2018).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Umukoro, S., Ben-Azu, B., Ajayi, A.M. et al. Cymbopogon citratus mitigates neurobehavioral impairments via inhibition of oxidative stress and inflammatory changes in mice submitted to complete Freund adjuvant. Nutrire 46, 3 (2021).

Download citation


  • Cymbogogon citratus
  • Neurological deficits
  • Inflammatory cytokines
  • Oxidative stress
  • Complete Freund adjuvant