Antinociceptive Effect of the Polygala sabulosa Hydroalcoholic Extract in Mice: Evidence for the Involvement of Glutamatergic Receptors and Cytokine Pathways
Abstract
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-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were also investigated. P. sabulosa HE given orally produced a significant inhibition of glutamate-induced paw licking [ID50 = 530.3 (416.7–674.8) mg/kg and inhibition of 79 ± 6% at 1000 mg/kg]. The plant derivatives α-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, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, TNF-α and IL-1β, 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 α-spinasterol, scopoletin and styryl-2-pyrones play an important role on the antinociceptive effects of P. sabulosa HE.