Atividade antinociceptiva e anti-inflamatória de Piptadenia stipulacea (Benth.) Ducke (Fabaceae) e inibição de Cox por galetina 3,6-dimetil éter (FGAL)

Abstract

Piptadenia stipulacea belongs to the Fabaceae family,and is widely distributed in the caatinga. This species is commonly known in the Brazilian Northeast as “jurema-branca”, “carcará” and “rasga-beiço”, and is used in folk medicine in inflammation.In this study, we attempted to identify the possible antinociceptive and anti-inflammatory activities of the aqueous phase, the ethyl acetate phase and one flavonoid obtained from aerial parts of Piptadenia stipulacea. Aerial parts of Piptadenia stipulacea were used and after fractionation, the flavonoid Galetin 3,6-dimethyl ether(FGAL) was obtained of the chloroformic phase of this plant. Experiments were conducted on Swiss mice using the acetic acid-induced writhing test, the hot plate test, the formalintest and zymosan A-induced peritonitis test.To characterize the mechanism(s) responsible for these antinociceptive and anti-inflammatory actions of FGAL, COX inhibitor screening assay kit and test of DPPH was used. The aqueous and ethyl acetate phases (100 mg/kg, p.o.); and the flavonoid FGAL (100 μmol/kg, p.o. or i.p.), reduced the nociception produced by acetic acid, by 49,9 ± 11,2, 54,6 ± 5,3, 39,0 ± 6,8 and64,8% ± 8,1, respectively. As FGAL have greater antinociceptive activity when administered in traperitoneally comparedto oral route, we chose this route you follow up the study with FGAL.The ethyl acetate phase (100 mg/kg, p.o.) reduced nociception in the hot plate, indicating that this fraction exhibited central activity. The ethyl acetate phase (100 mg/kg, p.o.) reduced the formalin effects in both phases by 40,2± 10,3 and59,9% ± 6,5, respectively. Treatment with the aqueous phase (100 mg/kg, p.o.) and FGAL (100_mol/kg, i.p.) only protected the second phase by 78,5± 5,5 and 64,0% ± 8,0, respectively.In addition, it was observed in the zymosan A-induced peritonitis test that the aqueous phase, the ethyl acetate phase and FGAL exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 35,8 ± 4,9, 37,7 ± 6,2 and 31,3% ± 13,3, respectively. Moreover, FGAL at 0,2μM was able to inhibit COX-1 (79,5% ± 0,6) and COX-2 (56,0% ± 3,8), with an inhibition profile similar to indomethacin inthe same concentration(93.0 ±2.6and79.0±1.5%, respectively), showing in hibition of COX-1 in greater proportion than COX-2. Further more, in domethac in was more effective, both COX-1 and COX-2 when compared to FGAL. In the test of DPPH, FGAL showed high radical scavenging activity. These results in fer that the aqueous phase, the ethyl acetate phase and FGAL obtained from aerial parts of Piptadenia stipulacea are able to modulate the peripheral nociception and acute inflammatory response. The flavonoid FGAL in hibit COX-1 and COX-2, probably for its ability to scavenge free radicals, this being one of its mechanism of action in nociception and inflammation. More over, there sults corroborate the popular use of Piptadenia stipulacea by their anti-inflammatory property.