title: Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var. grisea.
abstract: In the present study, siaresinolic acid (siaresinol, SA) was isolated from the leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti-inflammatory activity. The antinociceptive effect of SA was investigated in mice using different animal models to study pain. In the acetic acid-induced writhing test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h before a pain stimulus significantly reduced the nociceptive response (by 42.3, 68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive effect induced by SA in the writhing test, suggesting that the K(+)ATP channel pathway might be involved in its mechanism of action. In the formalin test, SA (1 mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating an anti-inflammatory effect. In the hot plate test, there was no significant difference in nociceptive behavior. In the rota-rod test, it was verified that a high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice. In the pleurisy model, induced by carrageenan, treatment with SA inhibited important events involved in inflammatory responses, namely leukocyte influx, plasma leakage, and increased inflammatory mediators (TNF-α, IL-1β, and chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at concentrations ranging from 1 to 200 μg/mL. These results suggest, for the first time, that SA attenuates nociceptive behavior through mechanisms involving receptors for ATP-dependent potassium channels, in addition to suppressing acute inflammatory responses.
authors.affiliation: Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Maceió, AL, 57072-970, Brazil.
authors.forename: Anderson Marques
authors.initials: AM
authors.lastname: de Oliveira
authors.forename: Almair Ferreira
authors.initials: AF
authors.lastname: de Araújo
authors.forename: Rosangela P
authors.initials: RP
authors.lastname: Lyra Lemos
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Conserva
authors.forename: Jamylle Nunes
authors.initials: JN
authors.lastname: de Souza Ferro
authors.forename: Emiliano
authors.initials: E
authors.lastname: Barreto
mesh_terms: D000700:Analgesics / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002351:Carrageenan; D004195:Disease Models, Animal; D005557:Formaldehyde; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D019666:Rubiaceae / Q000737:chemistry*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D010936:Plant Extracts; D015221:Potassium Channels; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D002351:Carrageenan