A Naphthoquinone from Sinningia canescens Inhibits Inflammation and Fever in Mice

Abstract

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.

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Acknowledgments

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).

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Correspondence to Aleksander R. Zampronio.

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Fig. S1.

Effect of dichloromethane and hexane fractions of S. canescens on carrageenan (Cg)-induced paw edema, mechanical hyperalgesia, and lipopolysaccharide-induced fever. (a-d) Mice were treated with the dichloromethane fraction (DCM; 2.5 mg/kg), hexane fraction (HEX; 2.0 mg/kg), indomethacin (IND; 5 mg/kg), or vehicle (V) orally or dexamethasone (DEX; 1 mg/kg) subcutaneously. One hour after oral treatment or 30 min after subcutaneous treatment, the animals received Cg (300 μg/paw). Edema formation was evaluated for up to 4 h after the Cg injection (a, b), and the mechanical threshold was evaluated before any injection (BASAL) and 3 h after the Cg injection (c, d). (e, f) Animals were treated with the same doses of the fractions and IND orally and after 30 min received LPS (100 μg/kg, i.p.). Body temperature was measured up to 6 h after the LPS injection. The data are expressed as the mean ± SEM change in paw thickness (in micrometers) (a, b), mechanical threshold (in milligrams) (c, d), or body temperature (°C) (e, f) (n = 6-14). The data were analyzed using two-way ANOVA (a, b, e, f) or one-way ANOVA (c, d) followed by Bonferroni’s post hoc test. Symbols denote significant differences compared with the basal threshold, V/V-treated group (### p < 0.001), or V/CG- or V/LPS-treated group (*p < 0.05, **p < 0.01) (PDF 95 kb)

Fig. S2.

Fingerprint analysis of the DCM and HEX fractions obtained from the tubers of S. canescens. Figure shows the presence of MHD (1) identified by HPLC in HEX and DCM fractions. MHD was observed in both fractions at 54.1 min (PDF 87 kb)

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Lomba, L.A., Vogt, P.H., Souza, V.E.P. et al. A Naphthoquinone from Sinningia canescens Inhibits Inflammation and Fever in Mice. Inflammation 40, 1051–1061 (2017). https://doi.org/10.1007/s10753-017-0548-y

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KEY WORDS

  • Sinningia canescens
  • Gesneriaceae
  • inflammation
  • naphthoquinone
  • 6-methoxi-7-hidroxy-α-dunnione