Original Article

The effect of carvacrol on respiratory syncytial virus infection in mice model: caution in the use of herbal medicines


Background and Objectives: Respiratory syncytial virus (RSV) is one of the most common viruses associated with acute lower respiratory tract infections in infants, young children, and the elderly. Due to a lack of effective anti-viral drugs or vaccines, using an immunomodulatory strategy is probably the best option to decrease the burden of RSV disease. Here, we studied carvacrol as a known immunomodulator on RSV infection outcome in a mice model.
Materials and Methods: Balb/c mice were infected by intranasal inoculation of RSV-A2, and treatment started daily 24 h after infection. Mice were sacrificed on day five after infection and experimental analyses were performed to study airway immune cell influx, CD4 and CD8 subtypes, cytokine/chemokine secretion, lung histopathology, and viral load.
Results: Results showed that using carvacrol enhanced immune cell influx, cytokine/chemokine production, and virus titer, and aggravated lung pathology. Our result showed that carvacrol administration increased viral titer compared to the RSV-PBS group. Also, carvacrol significantly induced IFN-γ production and did not induce IL-10 production. Besides, carvacrol non-significantly increased lymphocytes and monocytes count but did not affect the neutrophil count.
Conclusion: Carvacrol at the concentration of 80 (mg/kg) did not show immunomodulatory activity to alleviate the RSV infection outcome. Further research is needed to uncover the effects of the carvacrol intervention on virus replication and immune responses following RSV infection. Many herbal remedies in use contain carvacrol. However, the use of herbal remedies to treat viral respiratory infections such as RSV has to be performed with caution.

1. Schmidt ME, Varga SM. Modulation of the host immune response by respiratory syncytial virus proteins. J Microbiol 2017;55:161-171.
2. van Drunen Littel-van den Hurk S , Mapletoft JW, Arsic N, Kovacs‐Nolan J. Immunopathology of RSV infection: prospects for developing vaccines without this complication. Rev Med Virol 2007;17:5-34.
3. Straliotto SM, Siqueira MM, Machado V, Maia TM. Respiratory viruses in the pediatric intensive care unit: prevalence and clinical aspects. Mem Inst Oswaldo Cruz 2004;99:883-887.
4. Scheltema NM, Gentile A, Lucion F, Nokes DJ, Munywoki PK, Madhi SA, et al. Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series. Lancet Glob Health 2017;5(10):e984-e991.
5. Piedimonte G, Simoes EA. Respiratory syncytial virus and subsequent asthma: one step closer to unravelling the Gordian knot? Eur Respir J 2002;20:515-517.
6. Collins PL, Melero JA. Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years. Virus Res 2011;162:80-99.
7. Rosenberg HF, Domachowske JB. Inflammatory responses to respiratory syncytial virus (RSV) infection and the development of immunomodulatory pharmacotherapeutics. Curr Med Chem 2012;19:1424-1431.
8. Tahamtan A, Askari FS, Bont L, Salimi V. Disease severity in respiratory syncytial virus infection: role of host genetic variation. Rev Med Virol 2019;29(2):e2026.
9. Tahamtan A, Samieipoor Y, Nayeri FS, Rahbarimanesh AA, Izadi A, Rashidi-Nezhad A, et al. Effects of cannabinoid receptor type 2 in respiratory syncytial virus infection in human subjects and mice. Virulence 2018;9:217-230.
10. Hayatdavoudi P, Khajavi Rad A, Rajaei Z, Hadjzadeh MA. Renal injury, nephrolithiasis and Nigella sativa: a mini review. Avicenna J Phytomed 2016;6:1-8.
11. Friedman M. Chemistry and multibeneficial bioactivities of carvacrol (4-isopropyl-2-methylphenol), a component of essential oils produced by aromatic plants and spices. J Agric Food Chem 2014;62:7652-7670.
12. Lima Mda S, Quintans-Júnior LJ, de Santana WA, Kaneto CM, Pereira Soares MB , Villarreal CF. Anti-inflammatory effects of carvacrol: evidence for a key role of interleukin-10. Eur J Pharmacol 2013;699:112-117.
13. Feng X, Jia A. Protective effect of carvacrol on acute lung injury induced by lipopolysaccharide in mice.
Inflammation 2014;37:1091-1101.
14. Kianmehr M, Rezaee A, Mahmoudi M, Ghorani V, Boskabady MH. T helper cells subtypes and their cytokine gene expression affected by carvacrol in sensitized mice administered during sensitization period. J Cell Biochem 2019;120:5343-5354.
15. Salimi V, Hennus MP, Mokhtari-Azad T, Shokri F, Janssen R, Hodemaekers HM, et al. Opioid receptors control viral replication in the airways. Crit Care Med 2013;41:205-214.
16. Shirey KA, Pletneva LM, Puche AC, Keegan AD, Prince GA, Blanco JC, et al. Control of RSV-induced lung injury by alternatively activated macrophages is IL-4Ralpha-, TLR4-, and IFN-beta -dependent. Mucosal Immunol 2010;3:291-300.
17. de Carvalho FO, Silva ÉR, Gomes IA, Santana HSR, do Nascimento Santos DKD, de Oliveira Souza GP, et al. Anti‐inflammatory and antioxidant activity of carvacrol in the respiratory system: a systematic review and meta‐analysis. Phytother Res 2020;34:2214-2229.
18. Rajabli N, Williamson L, Nimmer PS, Kelly-Worden M, Bange JS, Ho Y, et al. The dangers of sublethal carvacrol exposure: increases in virulence of Bacillus cereus during endophthalmitis. Int J Biochem Mol Biol 2018;9:11-21.
19. Stojanović NM, Stevanović M, Randjelović P, Mitić K, Petrović V, Sokolović D, et al. Low dose of carvacrol prevents rat pancreas tissue damage after L-arginine application, while higher doses cause pancreatic tissue impairment. Food Chem Toxicol 2019;128:280-285.
20. Alunno A, Carubbi F, Rodríguez-Carrio J. Storm, typhoon, cyclone or hurricane in patients with COVID-19? beware of the same storm that has a different origin. RMD Open 2020;6(1):e001295.
21. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020;395:473-475.
22. Mahmoodi M, Amiri H, Ayoobi F, Rahmani M, Taghipour Z, Ghavamabadi RT, et al. Carvacrol ameliorates experimental autoimmune encephalomyelitis through modulating pro-and anti-inflammatory cytokines. Life Sci 2019;219:257-263.
23. Guimarães AG, Xavier MA, de Santana MT, Camargo EA, Santos CA, Brito FA, et al. Carvacrol attenuates mechanical hypernociception and inflammatory response. Naunyn Schmiedebergs Arch Pharmacol 2012;385:253-263.
24. Khazdair MR, Anaeigoudari A, Hashemzehi M, Mohebbati R. Neuroprotective potency of some spice herbs, a literature review. J Tradit Complement Med 2018;9:98-105.
25. Yang Y. Use of herbal drugs to treat COVID-19 should be with caution. Lancet 2020;395:1689-1690.
26. Wang Y, Zeng X, Zhao Y, Chen W, Chen YZ. The pros and cons of traditional Chinese medicines in the treatment of COVID-19. Pharmacol Res 2020;157:104873.
IssueVol 13 No 5 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v13i5.7438
Human respiratory syncytial virus; Carvacrol; Immunomodulation; Interferon-gamma; Interleukin-10

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Faraji-Zonouz M, Khodakhah F, Tavakoli F, Tahamtan A, Tavakoli-Yaraki M, Rezaie F, Mokhatri-Azad T, Salimi V. The effect of carvacrol on respiratory syncytial virus infection in mice model: caution in the use of herbal medicines. Iran J Microbiol. 2021;13(5):712-717.