A Naphthoquinone from Sinningia canescens Inhibits Inflammation and Fever in Mice.
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 KATPchannel 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.
Department of Pharmacology, Biological Sciences Section, Federal University of Paraná, Centro Politécnico, PO Box 19031, Curitiba, PR, 81531-980, Brazil.
Luís A
LA
Lomba
Department of Pharmacology, Biological Sciences Section, Federal University of Paraná, Centro Politécnico, PO Box 19031, Curitiba, PR, 81531-980, Brazil.
Paulo H
PH
Vogt
Department of Pharmacology, Biological Sciences Section, Federal University of Paraná, Centro Politécnico, PO Box 19031, Curitiba, PR, 81531-980, Brazil.
Victor E P
VEP
Souza
Department of Pharmacology, Biological Sciences Section, Federal University of Paraná, Centro Politécnico, PO Box 19031, Curitiba, PR, 81531-980, Brazil.
Mariane C G
MCG
Leite-Avalca
Department of Chemistry, Federal University of Paraná, Centro Politécnico, PO Box 19081, Curitiba, PR, 81530-900, Brazil.
Maria H
MH
Verdan
Department of Chemistry, Federal University of Paraná, Centro Politécnico, PO Box 19081, Curitiba, PR, 81530-900, Brazil.
Maria Elida A
MEA
Stefanello
Department of Pharmacology, Biological Sciences Section, Federal University of Paraná, Centro Politécnico, PO Box 19031, Curitiba, PR, 81531-980, Brazil. aleksander@ufpr.br.
Aleksander R
AR
Zampronio
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification; D058633:Antipyretics / Q000302:isolation & purification; D016207:Cytokines / Q000037:antagonists & inhibitors; D005334:Fever / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy* / Q000517:prevention & control; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011453:Prostaglandins / Q000378:metabolism
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D058633:Antipyretics; D016207:Cytokines; D009285:Naphthoquinones; D010936:Plant Extracts; D011453:Prostaglandins
6-methoxi-7-hidroxy-α-dunnione; Gesneriaceae; Sinningia canescens; inflammation; naphthoquinone