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 KATP channel blocker, did not alter the analgesic effect of MHD. Lipopolysaccharide-induced fever and TNF-α, interleukin-1ß, 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.

Naphthochromenes and Related Constituents from the Tubers of Sinningia allagophylla.

Chemical investigation of the tubers of Sinningia allagophylla led to the isolation of two new chromenes, (2S)-12-hydroxylapachenole (1) and (3R)-3,4-dihydro-3-hydroxy-4-oxo-8-methoxylapachenole (2), and three new dimeric chromenes, allagophylldimers A-C (3-5). Thirteen known compounds, 6-methoxy-7,8-benzocoumarin (6), lapachenole, 8-methoxylapachenole, tectoquinone, 7-hydroxytectoquinone, dunniol, α-dunnione, dunnione, 8-hydroxydunnione, aggregatin E, cedrol, oleanolic acid, and halleridone, were also identified. 6-Methoxy-7,8-benzocoumarin (6) has been isolated for the first time from a natural source.

Antinociceptive activity of the ethanolic extract, fractions, and aggregatin D isolated from Sinningia aggregata tubers.

The present study investigated the effects of the ethanolic extract (ESa), fractions, and compounds isolated from Sinningia aggregata in male Swiss mice on carrageenan-induced paw edema, neutrophil migration, mechanical hyperalgesia, formalin-induced nociception, and lipopolysaccharide-induced fever. The ESa did not alter edema, neutrophil migration, or fever at any of the doses tested. However, the ESa reduced phase II of formalin-induced nociception and carrageenan-induced mechanical hyperalgesia. The petroleum ether (PE) and ethyl acetate (EA) fractions and aggregatin D (AgD; isolated from the EA fraction) reduced formalin-induced nociception. Anthraquinones from the PE fraction were ineffective. AgD also inhibited carrageenan-induced mechanical hyperalgesia. Neither the ESa nor AgD altered thermal nociception or motor performance. Local administration of AgD also reduced hyperalgesia induced by carrageenan, bradykinin, tumor necrosis factor-α, interleukin-1ß, cytokine-induced neutrophil chemoattractant, prostaglandin E2, and dopamine but not hyperalgesia induced by forskolin or dibutyryl cyclic adenosine monophosphate. The positive control dipyrone reduced the response induced by all of the stimuli. Additionally, glibenclamide abolished the analgesic effect of dipyrone but not the one induced by AgD. AgD did not change lipopolysaccharide-induced nitric oxide production by macrophages or the nociception induced by capsaicin, cinnamaldehyde, acidified saline, or menthol. These results suggest that the ESa has important antinociceptive activity, and this activity results at least partially from the presence of AgD. AgD reduced mechanical hyperalgesia induced by several inflammatory mediators through mechanisms that are different from classic analgesic drugs.