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-1 β (IL-1 β ) and tumour necrosis factor-α (TNF-α ) were also investigated. P. sabulosa HE given orally produced a significant inhibition of glutamateinduced paw licking ) 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-1 β , 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-aminocyclopentanetrans -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.The plants of genus Polygala are widely distributed in Santa Catarina state, Brazil, and have been employed to treat disorders of the bowel and kidney, as a topical anaesthetic and expectorant [1]. Scientific studies in isolated cells and in animals have confirmed the biological activities of the plants from genus Polygala [2-10]. The chemical constituents of Polygala , coumarins, steroids, saponins, lignans, flavonoids and xanthones confer to these plants valuable pharmacological properties [7][8][9][10][11][12][13].Recently, we have demonstrated that Polygala sabulosa hydroalcoholic extract (HE) A. W. Bennett (Polygalaceae) produced antinociceptive action against the acetic acidinduced visceral nociception. The presence of styryl-2-pyrones, coumarin (scopoletin) and steroid ( α -spinasterol) gives to the plant a potent antinociceptive effect [9]. However, the model of nociception previously employed did not allow to clearly identify the mechanism of the antinociceptive action of the plant extract. Indeed, the acetic acid-induced visceral nociception involves a chain of inflammatory mediators that are released into the abdominal cavity and in the central nervous system [14][15][16].In this concern, the aim of this study was to identify the mechanism by which P. sabulosa HE exerts its antinociceptive effect. For this purpose, the effects of the P. sabulosa HE we...

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