Trans-anethole, the major constituent of the essential oil of anise, improves the antiarthritic effects of methotrexate in rats

Authors

DOI:

https://doi.org/10.33448/rsd-v11i10.32582

Keywords:

Natural product; Inflammation; Arthritis; Oxidative stress.

Abstract

The aim of this study was to evaluate the effect of trans-anethole in combination with methotrexate, compared to monotherapy with trans-anethole or methotrexate, on inflammatory parameters and oxidative stress of arthritic rats. The experimental model of arthritis induced by Freund's complete adjuvant (AIA) in rats was used. Treatment with trans-anethole and methotrexate, in combination or monotherapy, was started on the day of AIA induction and continued for 21 days. The association of anethole (62.5 mg/Kg) to methotrexate (6 mg/Kg) therapy was able to further reduce both the oxidative stress induced by arthritis and the inflammatory events that characterize the disease, as demonstrated by the following indicators: 1) decrease in the edema of the hind legs, in the score of secondary lesions, in the recruitment of leukocytes to the articular cavity and in the plasma myeloperoxidase activity; 2) increase in plasma content of reduced thiols and total antioxidant capacity; 3) diminution of protein carbonylation in plasma, liver and kidneys; 4) decrease in lipid peroxidation in the liver; 5) reduction in the hepatic ROS content; 6) enhancement of the activity of the antioxidant enzymes and GSH/GSSG ratio. In general, the combination anethole + methotrexate presented a substantially higher effect than the monotherapy with anethole or methotrexate (at the same doses). The data obtained in this work allow us to conclude that the use of trans-anethole in combination with methotrexate suppressed arthritic progression in rats, with the main advantage of reduction of methotrexate dose, attenuating adverse effects caused by high dose therapy.

References

Alam, J., Jantan, I., & Bukhari, S. (2017). Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy. Biomedicine & Pharmacotherapy, 92, 615–633.

Ames, F. Q., Bracht, L., Schneider, L., Rocha, B. A., Santos, G. A., Lima, E. P., Rocha, E., Cuman, R., & Bersani-Amado, C. A. (2020). Anti-inflammatory Effect of Low-Dose Anethole and Ibuprofen Combination Is Accompanied by Partial Prevention of Hepatic Metabolic Changes in Arthritic Rats. Inflammation, 43(5), 1680–1691.

Batlouni, M. (2010). Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects. Arquivos Brasileiros de Cardiologia, 94, 556-563.

Bauerova, K., Paulovicova, E., Mihalova, D., Drafi, F., Strosova, M., Mascia, C., ... & Ponist, S. (2010). Combined methotrexate and coenzyme Q₁₀ therapy in adjuvant-induced arthritis evaluated using parameters of inflammation and oxidative stress. Acta Biochimica Polonica, 57(3).

Blumenthal, K. G., Lai, K. H., Huang, M., Wallace, Z. S., Wickner, P. G., & Zhou, L. (2017). Adverse and Hypersensitivity Reactions to Prescription Nonsteroidal Anti-Inflammatory Agents in a Large Health Care System. The journal of allergy and clinical immunology. In practice, 5(3), 737–743.e3.

Bradley, P. P., Priebat, D. A., Christensen, R. D., & Rothstein, G. (1982). Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. Journal of investigative dermatology, 78(3), 206-209.

Buege, J. A., & Aust, S. D. (1978). Microsomal lipid peroxidation. Methods in enzymology, 52, 302–310.

Chainy, G. B., Manna, S. K., Chaturvedi, M. M., & Aggarwal, B. B. (2000). Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF-kappaB, AP-1, JNK, MAPKK and apoptosis. Oncogene, 19(25), 2943–2950.

Chan, E. S., & Cronstein, B. N. (2013). Mechanisms of action of methotrexate. Bulletin of the NYU Hospital for Joint Diseases, 71(suppl 1), S5.

Comar, J. F., de Sá-Nakanishi, A. B., de Oliveira, A. L., Wendt, M. M. N., Amado, C. A. B., Iwamoto, E. L. I., ... & Bracht, A. (2013). Oxidative state of the liver of rats with adjuvant-induced arthritis. Free Radical Biology and Medicine, 58, 144-153.

Correa, V. G., de Sá-Nakanishi, A. B., Gonçalves, G. A., Barros, L., Ferreira, I., Bracht, A., & Peralta, R. M. (2019). Yerba mate aqueous extract improves the oxidative and inflammatory states of rats with adjuvant-induced arthritis. Food & function, 10(9), 5682–5696.

Daoussis, D., Panoulas, V. F., Antonopoulos, I., John, H., Toms, T. E., Wong, P., ... & Kitas, G. D. (2010). Cardiovascular risk factors and not disease activity, severity or therapy associate with renal dysfunction in patients with rheumatoid arthritis. Annals of the rheumatic diseases, 69(3), 517-521.

Erel O. (2004). A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical biochemistry, 37(4), 277–285.

Firestein G. S. (2003). Evolving concepts of rheumatoid arthritis. Nature, 423(6937), 356–361.

Fitsiou, E., Mitropoulou, G., Spyridopoulou, K., Tiptiri-Kourpeti, A., Vamvakias, M., Bardouki, H., ... & Pappa, A. (2016). Phytochemical profile and evaluation of the biological activities of essential oils derived from the Greek aromatic plant species Ocimum basilicum, Mentha spicata, Pimpinella anisum and Fortunella margarita. Molecules, 21(8), 1069.

Freire, R. S., Morais, S. M., Catunda-Junior, F. E., & Pinheiro, D. C. (2005). Synthesis and antioxidant, anti-inflammatory and gastroprotector activities of anethole and related compounds. Bioorganic & medicinal chemistry, 13(13), 4353–4358.

Gaies, E., Jebabli, N., Trabelsi, S., Salouage, I., Charfi, R., Lakhal, M., & Klouz, A. (2012). Methotrexate side effects: review article. Journal of Drug Metabolism & Toxicology, 3(4), 1-5.

Gomes, R. K. S., Pires, F. A., Nobre, M. R. C., Marchi, M. F. D. S., & Rickli, J. C. K. (2017). Impact of rheumatoid arthritis in the public health system in Santa Catarina, Brazil: a descriptive and temporal trend analysis from 1996 to 2009. Revista Brasileira de Reumatologia, 57, 204-209.

Hissin, P. J., & Hilf, R. (1976). A fluorometric method for determination of oxidized and reduced glutathione in tissues. Analytical biochemistry, 74(1), 214–226.

Levine, R. L., Garland, D., Oliver, C. N., Amici, A., Climent, I., Lenz, A. G., Ahn, B. W., Shaltiel, S., & Stadtman, E. R. (1990). Determination of carbonyl content in oxidatively modified proteins. Methods in enzymology, 186, 464–478.

Marklund, S., & Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European journal of biochemistry, 47(3), 469–474.

McCarberg, B., & Tenzer, P. (2013). Complexities in the pharmacologic management of osteoarthritis pain. Current medical research and opinion, 29(5), 539–548.

McGarry, T., Biniecka, M., Veale, D. J., & Fearon, U. (2018). Hypoxia, oxidative stress and inflammation. Free radical biology & medicine, 125, 15–24.

Moradi, J., Abbasipour, F., Zaringhalam, J., Maleki, B., Ziaee, N., Khodadoustan, A., & Janahmadi, M. (2014). Anethole, a Medicinal Plant Compound, Decreases the Production of Pro-Inflammatory TNF-α and IL-1β in a Rat Model of LPS-Induced Periodontitis. Iranian journal of pharmaceutical research : IJPR, 13(4), 1319–1325.

Mota, L. M. H. D., Cruz, B. A., Brenol, C. V., Pereira, I. A., Rezende-Fronza, L. S., Bertolo, M. B., ... & Pinheiro, G. D. R. C. (2013). Guidelines for the drug treatment of rheumatoid arthritis. Revista brasileira de reumatologia, 53, 158-183.

Ritter, A. M., Ames, F. Q., Otani, F., de Oliveira, R. M., Cuman, R. K., & Bersani-Amado, C. A. (2014). Effects of anethole in nociception experimental models. Evidence-based complementary and alternative medicine: eCAM, 2014, 345829.

Ritter, A., Hernandes, L., da Rocha, B. A., Estevão-Silva, C. F., Wisniewski-Rebecca, E. S., Cezar, J., Caparroz-Assef, S. M., Cuman, R., & Bersani-Amado, C. A. (2017). Anethole reduces inflammation and joint damage in rats with adjuvant-induced arthritis. Inflammation research : official journal of the European Histamine Research Society ... [et al.], 66(8), 725–737.

Rodrigues Siqueira, I., Fochesatto, C., da Silva Torres, I. L., Dalmaz, C., & Alexandre Netto, C. (2005). Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats. Life sciences, 78(3), 271–278.

Rosenthale M. E. (1970). A comparative study of the Lewis and Sprague Dawley rat in adjuvant arthritis. Archives internationales de pharmacodynamie et de therapie, 188(1), 14–22.

Sá-Nakanishi, A. B., Soni-Neto, J., Moreira, L. S., Gonçalves, G. A., Silva, F., Bracht, L., Bersani-Amado, C. A., Peralta, R. M., Bracht, A., & Comar, J. F. (2018). Anti-Inflammatory and Antioxidant Actions of Methyl Jasmonate Are Associated with Metabolic Modifications in the Liver of Arthritic Rats. Oxidative medicine and cellular longevity, 2018, 2056250.

Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry, 25(1), 192–205.

Segal, R., Yaron, M., & Tartakovsky, B. (1990). Methotrexate: mechanism of action in rheumatoid arthritis. Seminars in arthritis and rheumatism, 20(3), 190–200.

Senatore, F., Oliviero, F., Scandolera, E., Taglialatela-Scafati, O., Roscigno, G., Zaccardelli, M., & De Falco, E. (2013). Chemical composition, antimicrobial and antioxidant activities of anethole-rich oil from leaves of selected varieties of fennel [Foeniculum vulgare Mill. ssp. vulgare var. azoricum (Mill.) Thell]. Fitoterapia, 90, 214–219.

Silva, M. A., Ishii-Iwamoto, E. L., Bracht, A., Caparroz-Assef, S. M., Kimura, E., Cuman, R. K., & Bersani-Amado, C. A. (2005). Efficiency of combined methotrexate/chloroquine therapy in adjuvant-induced arthritis. Fundamental & clinical pharmacology, 19(4), 479–489.

Stamp, L. K., Chapman, P. T., O'Donnell, J. L., Zhang, M., James, J., Frampton, C., Barclay, M. L., Kennedy, M. A., & Roberts, R. L. (2010). Polymorphisms within the folate pathway predict folate concentrations but are not associated with disease activity in rheumatoid arthritis patients on methotrexate. Pharmacogenetics and genomics, 20(6), 367–376.

Tak, P. P., Zvaifler, N. J., Green, D. R., & Firestein, G. S. (2000). Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases. Immunology today, 21(2), 78–82.

Tawfik, M. K. (2015). Combination of coenzyme Q10 with methotrexate suppresses Freund's complete adjuvant-induced synovial inflammation with reduced hepatotoxicity in rats: Effect on oxidative stress and inflammation. International Immunopharmacology, 24(1), 80-87.

Wessels, J. A. M., Huizinga, T. W. J., & Guchelaar, H. J. (2008). Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology, 47(3), 249-255.

Winder, C. V., Wax, J., & Been, M. A. (1957). Rapid foot volume measurements on unanesthetized rats, and the question of a phenylbutazone effect on anaphylactoid edema. Archives internationales de pharmacodynamie et de therapie, 112(1-2), 174–187.

Wisniewski-Rebecca, E. S., Rocha, B. A., Wiirzler, L. A., Cuman, R. K., Velazquez-Martinez, C. A., & Bersani-Amado, C. A. (2015). Synergistic effects of anethole and ibuprofen in acute inflammatory response. Chemico-Biological Interactions, 242, 247-253.

Yang, J. F., Yang, C. H., Chang, H. W., Yang, C. S., Wang, S. M., Hsieh, M. C., & Chuang, L. Y. (2010). Chemical composition and antibacterial activities of Illicium verum against antibiotic-resistant pathogens. Journal of medicinal food, 13(5), 1254-1262.

Zimmerman, M. C., Clemens, D. L., Duryee, M. J., Sarmiento, C., Chiou, A., Hunter, C. D., ... & Anderson, D. R. (2017). Direct antioxidant properties of methotrexate: inhibition of malondialdehyde-acetaldehyde-protein adduct formation and superoxide scavenging. Redox biology, 13, 588-593.

Downloads

Published

27/07/2022

How to Cite

BONETTI, C. I. .; MOREIRA , J. J. da S. .; ROCHA, E. M. T. da .; MOREIRA, E. S. .; COMAR, J. F. .; SÁ-NAKANISHI, A. B. de .; BRACHT, A. .; BERSANI-AMADO, C. A. .; BRACHT, L. . Trans-anethole, the major constituent of the essential oil of anise, improves the antiarthritic effects of methotrexate in rats. Research, Society and Development, [S. l.], v. 11, n. 10, p. e197111032582, 2022. DOI: 10.33448/rsd-v11i10.32582. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/32582. Acesso em: 18 nov. 2024.

Issue

Section

Health Sciences