Antinociceptive effect of the Polygala sabulosa hydroalcoholic extract in mice: evidence for the involvement of glutamatergic receptors and cytokine pathways.
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.
Ribas
Camila M
CM
Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
Meotti
Flavia C
FC
Nascimento
Francisney P
FP
Jacques
Amanda V
AV
Dafre
Alcir L
AL
Rodrigues
Ana Lúcia S
AL
Farina
Marcelo
M
Soldi
Cristian
C
Mendes
Beatriz G
BG
Pizzolatti
Moacir G
MG
Santos
Adair R S
AR
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
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