title: Antinociceptive effect of the Polygala sabulosa hydroalcoholic extract in mice: evidence for the involvement of glutamatergic receptors and cytokine pathways.
abstract: This study investigated the role of the glutamatergic system on the antinociception caused by Polygala sabulosa hydroalcoholic extract (HE). The systems mediated by substance P, capsaicin, interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) were also investigated. P. sabulosa HE given orally produced a significant inhibition of glutamate-induced paw licking [ID(50) = 530.3 (416.7-674.8) mg/kg and inhibition of 79 +/- 6% at 1000 mg/kg]. The plant derivatives alpha-spinasterol, scopoletin and styryl-2-pyrones (compound 1 and 3) (10 mg/kg, intraperitoneally) inhibited 80 +/- 7%, 46 +/- 11%, 45 +/- 11% and 35 +/- 13% the nociceptive response caused by glutamate, respectively. Furthermore, P. sabulosa HE (500 mg/kg, orally) caused marked inhibition of nociceptive response induced by intrathecal injection of glutamate, N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, TNF-alpha and IL-1beta, with inhibitions of 44 +/- 7%, 55 +/- 4%, 38 +/- 10%, 61 +/- 7%, 76 +/- 9% and 100%, respectively. In contrast, P. sabulosa HE (500 mg/kg, orally) did not affect the biting response induced by the metabotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid, substance P and capsaicin. The locomotor activity was altered only in mice treated with a very high dose (1000 mg/kg) of P. sabulosa HE. Our results showed that the antinociceptive effects of P. sabulosa HE are associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. The plant derivatives alpha-spinasterol, scopoletin and styryl-2-pyrones play an important role on the antinociceptive effects of P. sabulosa HE.
authors.affiliation: Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Ribas
authors.forename: Flavia C
authors.initials: FC
authors.lastname: Meotti
authors.forename: Francisney P
authors.initials: FP
authors.lastname: Nascimento
authors.forename: Amanda V
authors.initials: AV
authors.lastname: Jacques
authors.forename: Alcir L
authors.initials: AL
authors.lastname: Dafre
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Cristian
authors.initials: C
authors.lastname: Soldi
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Mendes
authors.forename: Moacir G
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D031801:Polygala / Q000737:chemistry*; D017470:Receptors, Glutamate / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D013373:Substance P / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000700:Analgesics; D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D053583:Interleukin-1beta; D010936:Plant Extracts; D017470:Receptors, Glutamate; D018040:Receptors, Neurokinin-1; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D002211:Capsaicin