A Naphthoquinone from Sinningia canescens Inhibits Inflammation and Fever in Mice
- 204 Downloads
We previously showed that plants from the genus Sinningia are a source of antiinflammatory and analgesic compounds with different mechanisms of action. The present study evaluated the antiinflammatory, antinociceptive, and antipyretic effects of a crude extract (CE) from Sinningia canescens, its fractions, and 6-methoxy-7-hydroxy-α-dunnione (MHD) in mice. These effects were evaluated using carrageenan (Cg)-induced paw edema, acetic acid- and formalin-induced nociception, mechanical hyperalgesia, lipopolysaccharide (LPS)-induced fever, and plasma cytokine levels. The CE and dichloromethane and hexane fractions reduced Cg-induced paw edema and hyperalgesia, LPS-induced fever, and plasma tumor necrosis factor-α (TNF-α) levels. The CE also reduced acetic acid-induced writhing and the second phase of formalin-induced nociception but did not alter thermal nociception or motor performance. Partition with solvents showed that the antiinflammatory, antihyperalgesic, and antipyretic activities were present in dichoromethane and hexane fractions, and the major compound isolated from these fractions was MHD. Oral and intraplantar MHD administration reduced paw edema. Oral MHD administration also reduced prostaglandin E2-induced hyperalgesia but did not alter hyperalgesia that was induced by dopamine and dibutyryl cyclic adenosine monophosphate. Treatment with glibenclamide, a KATP channel blocker, did not alter the analgesic effect of MHD. Lipopolysaccharide-induced fever and TNF-α, interleukin-1β, and interleukin-6 levels were inhibited by MHD. Altogether, these data suggest that the CE has antiinflammatory, analgesic, and antipyretic activity, and these actions are at least partially related to MHD. These results also suggest that MHD acts by blocking cytokine synthesis and/or blocking prostaglandin activity.
KEY WORDSSinningia canescens Gesneriaceae inflammation naphthoquinone 6-methoxi-7-hidroxy-α-dunnione
This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 304668/2011-7 and 473873/2011-7). Lomba, L.A. is the recipient of a scholarship from Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were conducted.
- 3.Barbosa, F.L., L.S. Mori, D. Riva, M.E. Stefanello, and A.R. Zampronio. 2013. Antinociceptive and anti-inflammatory activities of the ethanolic extract, fractions and 8-methoxylapachenol from Sinningia allagophylla tubers. Basic & Clinical Pharmacology & Toxicology 113 (1): 1–7. doi: 10.1111/bcpt.12051.CrossRefGoogle Scholar
- 8.Cunha, T.M., W.A. Verri Jr., J.S. Silva, S. Poole, F.Q. Cunha, and S.H. Ferreira. 2005. A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proceedings of the National Academy of Sciences of the United States of America 102: 1755–1760.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.DiMartino, M. J., Campbell, G. K. Jr., Wolff C. E, Hanna, N. 1987. The pharmacology of arachidonic acid-induced rat paw edema. (0065-4299).Google Scholar
- 14.Dormond, O., M. Bezzi, A. Mariotti, and C. Ruegg. 2002. Prostaglandin E-2 promotes integrin alpha(V)beta(3)-dependent endothelial cell adhesion, Rac-activation, and spreading through cAMP/PKA-dependent signaling. The Journal of Biological Chemistry 277 (48): 45838–45846. doi: 10.1074/jbc.M209213200.CrossRefPubMedGoogle Scholar
- 17.Kassuya, C.A., A. Cremoneze, L.F. Barros, A.S. Simas, R. Lapa Fda, R. Mello-Silva, M.E. Stefanello, and A.R. Zampronio. 2009. Antipyretic and anti-inflammatory properties of the ethanolic extract, dichloromethane fraction and costunolide from Magnolia ovata (Magnoliaceae). Journal of Ethnopharmacology 124 (3): 369–376.CrossRefPubMedGoogle Scholar
- 18.Koster, R, M Anderson, and EJ De Beer. 1959. Acetic acid-induced analgesic screening: Fed Proc.Google Scholar
- 23.Parmentier, J.H., M.M. Muthalif, A.E. Saeed, and K.U. Malik. 2001. Phospholipase D activation by norepinephrine is mediated by 12(s)-, 15(s)-, and 20-hydroxyeicosatetraenoic acids generated by stimulation of cytosolic phospholipase a2. tyrosine phosphorylation of phospholipase d2 in response to norepinephrine. The Journal of Biological Chemistry 276 (19): 15704–15711. doi: 10.1074/jbc.M011473200.CrossRefPubMedGoogle Scholar
- 25.Rudaya, A.Y., A.A. Steiner, J.R. Robbins, A.S. Dragic, and A.A. Romanovsky. 2005. Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the dose and ambient temperature. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 289 (5): R1244–R1252.CrossRefPubMedGoogle Scholar
- 27.Scott, P.A., G.H. Kingsley, C.M. Smith, E.H. Choy, and D.L. Scott. 2007. Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials. Annals of the Rheumatic Diseases 66 (10): 1296–1304. doi: 10.1136/ard.2006.068650.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Souza, G.V., A.S. Simas, A.L. Bastos-Pereira, G.R. Frois, J.L. Ribas, M.H. Verdan, C.A. Kassuya, M.E. Stefanello, and A.R. Zampronio. 2015. Antinociceptive activity of the ethanolic extract, fractions, and aggregatin D isolated from Sinningia aggregata tubers. PloS One 10 (2): e0117501. doi: 10.1371/journal.pone.0117501.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Tanaka, S., S. Nishiumi, M. Nishida, Y. Mizushina, K. Kobayashi, A. Masuda, T. Fujita, et al. 2010. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-kappaB activation. Clinical and Experimental Immunology 160 (2): 283–292. doi: 10.1111/j.1365-2249.2009.04083.CrossRefPubMedPubMedCentralGoogle Scholar