title: Antinociceptive and anti-inflammatory effects of myricetin 3-O-β-galactoside isolated from Davilla elliptica: involvement of the nitrergic system.
abstract: We aimed to study the antinociceptive effects of myricetin 3-O-β-galactoside (Mi), a substance isolated from the hydroalcoholic extract of Davilla elliptica. This study examined male Swiss mice, inducible nitric oxide synthase C57B16/J knockout mice (iNOS(-/-)), and their corresponding wild type (WT). Formalin and tail-flick tests were used to evaluate the nociceptive threshold, and the carrageenan-induced paw edema test was used as a model for inflammation. The following drugs were administered to investigate the involvement of the nitrergic and opioidergic systems: L-NAME, a nonspecific nitric oxide synthase (NOS) inhibitor; L-arginine (L-Arg), a precursor for the synthesis of nitric oxide (NO); D-arginine (D-Arg), an inactive isomer for the synthesis of NO; aminoguanidine (Am), an inducible nitric oxide synthase (iNOS) inhibitor; and naloxone, a nonselective antagonist of opioid receptors. The results showed that oral pretreatment with Mi caused a dose-dependent inhibition of the inflammatory phase of the formalin test and did not alter motor performance. Intraperitoneal injection of L-NAME caused a reduction in the licking time during the second phase of the formalin test. The administration of L-Arg (but not D-Arg) reversed the antinociceptive effect of L-NAME. Furthermore, pre-administration of aminoguanidine potentiated the antinociceptive effect. Mi did not cause an antinociceptive effect in iNOS knockouts and led to a reduction in the nitrite concentration in the paws of mice. Carrageenan-induced paw edema was reduced in Swiss mice and WT mice when compared to iNOS(-/-) mice. Pre-administration of naloxone (NLX) did not reverse the antinociceptive effect of Mi, excluding the opioidergic system as a mediator of the antinociceptive effect. Thus, the results suggest that the antinociceptive and anti-inflammatory effects of myricetin 3-O-β-galactoside are related to peripheral inhibition of nitric oxide synthesis, mainly iNOS.
authors.affiliation: Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-010, Brazil.
authors.forename: Adolfo de Oliveira
authors.initials: Ade O
authors.lastname: Azevedo
authors.forename: Jussara Júlia
authors.initials: JJ
authors.lastname: Campos
authors.forename: Giovane Galdino
authors.initials: GG
authors.lastname: de Souza
authors.forename: Clarice de Carvalho
authors.initials: Cde C
authors.lastname: Veloso
authors.forename: Igor Dimitri Gama
authors.initials: ID
authors.lastname: Duarte
authors.forename: Fernão Castro
authors.initials: FC
authors.lastname: Braga
authors.forename: Andrea de Castro
authors.initials: Ade C
authors.lastname: Perez
mesh_terms: D000700:Analgesics / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D004487:Edema / Q000188:drug therapy*; D005697:Galactosides / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D005697:Galactosides; C529904:myricetin-3-O-galactoside; D009569:Nitric Oxide