Anti-inflammatory and antinociceptive properties of the hydroalcoholic fractions from the leaves of Annona crassiflora Mart. in mice.

BACKGROUND: Annona crassiflora Mart., popularly known as "Araticum", is a native tree of the Brazilian Cerrado used in folk medicine for treatment of pain and inflammatory diseases. We proposed to analyze analgesic and anti-inflammatory properties of the filtrate (F1) and the precipitate (F2) of the hydroalcoholic fraction from the leaves of Annona crassiflora Mart. in mice. MATERIALS AND METHODS: Swiss mice were submitted to formalin-induced nociception test and tail-flick reflex test, to assess antinociceptive properties, and to the rota-rod test, for motor performance analyses. To evaluate anti-inflammatory properties, F1 and F2 were orally administered 1 h prior to the intrathoracic injection of carrageenan, zymosan, LPS, CXCL8, or vehicle in Balb/c mice and neutrophil infiltration was evaluated 4 h after injection. RESULTS: F1 and F2 reduced the licking time in the second phase of formalin-induced nociception test, but only F2 showed a dose-dependent response. Neither F1 nor F2 reduced the latency time in the tail-flick reflex test. In addition, motor performance alteration was not observed in F1- or F2-treated mice. F2 treatment significantly inhibited the neutrophilia induced by carrageenan, LPS, or CXCL8, but not zymosan. CONCLUSIONS: The experimental data demonstrated that hydroalcoholic fractions of Annona crassiflora Mart. leaves have remarkable anti-inflammatory and antinociceptive activities.

Chemical composition and anti-inflammatory activity of the leaves of Byrsonima verbascifolia.

An ethnopharmacological survey indicates that the genus Byrsonima has some medicinal species that are commonly found in the Brazilian Cerrado and has been used as an anti-inflammatory and for gastroduodenal disorders. The aim of this study was to evaluate the anti-inflammatory and antioxidant activity along with qualitative chemical characterization of the methanolic extract of the leaves of Byrsonima verbascifolia (BvME) obtained by exhaustive percolation. The data from the chemical analyses by liquid chromatography-mass spectrometry led to tentative identification of 42 compounds belonging to proanthocyanidins, galloyl quinic acid derivatives, flavonoids, and triterpene glycoside derivatives. BvME contain flavonoids and show an antioxidative activity. The methanolic extract administered intraperitoneally at doses of 50, 100, or 300 mg/kg showed a significant reduction in paw edema and modulated the neutrophil influx in a mouse model. Furthermore, the anti-edematogenic activity of the extract provided in smaller doses (12.5 and 25 mg/kg) was also demonstrated in a mouse paw edema model. The extract inhibited NO production by macrophages induced by lipopolysaccharide. We presume that the anti-inflammatory effects of BvME are due to a combination of compounds present in B. verbascifolia, including catechins (procyanidins), flavonoids, and triterpene glycosides and that these anti-inflammatory actions should be mediated, at least partly, through the inhibition of NO production. This study supports and validates the ethnopharmacological uses of B. verbascifolia as an anti-inflammatory.

Tingenone, a pentacyclic triterpene, induces peripheral antinociception due to NO/cGMP and ATP-sensitive K(+) channels pathway activation in mice.

Substances derived from plants play an important role in the development of new analgesic drugs, among them, triterpenoids. The connection between the participation of L-arginine/NO/cGMP pathway and the activation of ATP-sensitive K(+) channels (KATP) has been established on the peripheral antinociception induced by various drugs. The study assessed the involvement of L-arginine/NO/cGMP/KATP pathway in the antinociceptive effect induced by tingenone, from Maytenus imbricata, against the hyperalgesia evoked by prostaglandin E2 (PGE2) in peripheral pathway. The paw pressure test was used, with hyperalgesia induced by intraplantar injection of PGE2 (2 µg). Tingenone (200 µg/paw) administered into the right hind paw induced a local antinociceptive effect, that was antagonized by l-NOArg, nonselective nitric oxide synthase (NOS) inhibitor and by L-NPA, selective neuronal NOS (nNOS) inhibitor. The L-NIO, selective inhibitor of endothelial (eNOS), and the L-NIL, selective inhibitor of inducible (iNOS), did not alter the peripheral antinociceptive effect of the tingenone. The ODQ, selective soluble guanylyl cyclase inhibitor, prevented the antinociceptive effect of tingenone, and zaprinast, inhibitor of the phosphodiesterase that is cyclic guanosine monophosphate (cGMP) specific, intensified the peripheral antinociceptive effect of the smaller dose of tingenone. Glibenclamide, ATP-sensitive K(+) channels (KATP) blocker, but not tetraethylammonium chloride, voltage-dependent K(+) channel blocker; dequalinium dichloride, blocker of the small conductance Ca(2+)-activated K(+) channel, and paxilline, a potent blocker of high-conductance Ca(2+)-activated K(+) channels, respectively, prevented the peripheral antinociceptive effect of tingenone. The results demonstrate that tingenone induced a peripheral antinociceptive effect by L-arginine/NO/cGMP/KATP pathway activation, with potential for a new analgesic drug.