Naphthoquinones of Sinningia reitzii and Anti-inflammatory/Antinociceptive Activities of 8-Hydroxydehydrodunnione.

Chemical investigation of the tubers of Sinningia reitzii led to the isolation of five new naphthoquinones, 8-hydroxydehydrodunnione (1), 7-hydroxydehydrodunnione (2), 5-hydroxy-6,7-dimethoxy-α-dunnione (3), 5-hydroxy-6,7-dimethoxydunniol (4), and 8-hydroxy-7-methoxy-2-O-methylstreptocarpone (5). Three known naphthoquinones, 7-hydroxy-α-dunnione, 8-hydroxydunnione, and 6,8-dihydroxy-7-methoxy-2-O-methyldunniol, were also identified. When tested for anti-inflammatory activity in a mouse model, compound 1 (50-500 pg/paw) reduced the edema induced by carrageenan in a dose-dependent fashion. The highest dose showed a similar inhibition to that observed for the positive control dexamethasone. At lower doses (5-10 pg/paw), 1 also dose dependently reduced the mechanical hyperalgesia induced by carrageenan. Compound 1 (15 pg/paw) abolished the mechanical hyperalgesia induced by prostaglandin E2 and dopamine, but not that induced by dibutyryl cyclic AMP. Dipyrone (320 µg/paw) completely abolished the hyperalgesia induced by these algogens. Additionally, compound 1 did not alter heat-induced nociception. These results suggest that this new naphthoquinone exhibits important anti-inflammatory and antinociceptive activities, which is dissimilar to that of most known analgesics.

Evidence of substance P autocrine circuitry that involves TNF-α, IL-6, and PGE2 in endogenous pyrogen-induced fever.

Substance P (SP) is involved in fever that is induced by lipopolysaccharide (LPS) but not by interleukin-1ß or macrophage inflammatory protein-1α. Intracerebroventricular (i.c.v.) administration of the neurokinin-1 (NK1) receptor antagonist SR140333B in rats reduced fever that was induced by an i.c.v. injection of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), corticotropin-releasing factor (CRF), endothelin-1 (ET-1), and morphine (MOR). Furthermore, an i.c.v. injection of SP induced a febrile response that was inhibited by indomethacin concomitant with an increase in PGE2 levels in cerebrospinal fluid. Lipopolysaccharide and PGE2 caused higher expression and internalization of NK1 receptors in the hypothalamus which were prevented by SR140333B. These data suggest that SP is an important mediator of fever, in which it induces a prostaglandin-dependent response and is released after TNF-α, IL-6, PGE2, CRF, endogenous opioids, and ET-1.

Antinociceptive and anti-inflammatory activities of the ethanolic extract, fractions and 8-methoxylapachenol from Sinningia allagophylla tubers.

This study investigated the antinociceptive and anti-inflammatory activities of the ethanolic extract (EESAl), fractions and the compound 8-methoxylapachenol (8ML) obtained from the tubers of Sinningia allagophylla. Male Swiss mice were treated with EESAl (3-300 mg/kg) or vehicle by oral route (p.o.) 1 hr before the injection of formalin 2.5% or carrageenan (Cg) into the hind paw. EESAl (3-30 mg/kg) reduced the inflammatory phase of the nociceptive behaviour induced by formalin (around 65% for all doses). EESAl (3-300 mg/kg, p.o.) also reduced Cg-induced mechanical hyperalgesia and oedema in a dose-dependent fashion but did not change the hot-plate latency or the motor performance of the animals. Oral administration of petroleum ether fraction (PE, 3 mg/kg), but not in the methanolic fraction (30 mg/kg), reduced both Cg-induced oedema and hyperalgesia. Compound 8ML isolated from PE (1.8 mg/kg, p.o.) abolished Cg-induced hyperalgesia but also did not change hot-plate latency or motor performance of the animals. 8ML administration into the paw (0.75-750 pg) dose-dependently reduced Cg-induced hyperalgesia. 8ML (750 pg) also blocked the hyperalgesia induced by tumour necrosis factor (TNF-α), interleukin-1ß (IL-1ß) and prostaglandin E2 (PGE2 ) but failed to change the hyperalgesia induced by cytokine-induced neutrophil chemoattractant-1 (CINC-1) and dopamine (Dopa). These results suggest that EESAl has an important antinociceptive and anti-inflammatory activity, the former one related, at least in part, to the reduction in the hyperalgesia. Similarly, 8ML reduced Cg-induced oedema and mechanical hyperalgesia and seems to act in peripheral sites and on the prostaglandin rather than on the sympathetic component of the Cg-inflammatory hyperalgesia.

Effects of babassu nut oil on ischemia/reperfusion-induced leukocyte adhesion and macromolecular leakage in the microcirculation: observation in the hamster cheek pouch.

BACKGROUND: The babassu palm tree is native to Brazil and is most densely distributed in the Cocais region of the state of Maranhão, in northeastern Brazil. In addition to the industrial use of refined babassu oil, the milk, the unrefined oil and the nuts in natura are used by families from several communities of African descendants as one of the principal sources of food energy. The objective of this study was to evaluate the effects of babassu oil on microvascular permeability and leukocyte-endothelial interactions induced by ischemia/reperfusion using the hamster cheek pouch microcirculation as experimental model. METHODS: Twice a day for 14 days, male hamsters received unrefined babassu oil (0.02 ml/dose [BO-2 group], 0.06 ml/dose [BO-6 group], 0.18 ml/dose [BO-18 group]) or mineral oil (0.18 ml/dose [MO group]). Observations were made in the cheek pouch and macromolecular permeability increase induced by ischemia/reperfusion (I/R) or topical application of histamine, as well as leukocyte-endothelial interaction after I/R were evaluated. RESULTS: The mean value of I/R-induced microvascular leakage, determined during reperfusion, was significantly lower in the BO-6 and BO-18 groups than in the MO one (P < 0.001). In addition, histamine-induced increase of microvascular permeability was significantly less pronounced in BO groups compared to MO one. No significant differences among groups in terms of leukocyte adhesion, concentrations of tumor necrosis factor alpha, interleukin 1, and interleukin 6 were found. CONCLUSIONS: Our findings suggest that unrefined babassu oil reduced microvascular leakage and protected against histamine-induced effects in postcapillary venules and highlights that these almost unexploited nut and its oil might be secure sources of food energy.