Antinociceptive properties of the hydroalcoholic extract and preliminary study of a xanthone isolated from Polygala cyparissias (Polygalaceae)

Abstract

Polygala cyparissias (Polygalaceae) grows abundantly on Brazil's Atlantic coast, belonging to the typical underbrush vegetation of dunes and have been used in folk medicine for treatment of several diseases, such as disturbances of bowel and kidney. The hydroalcoholic extract of P. cyparissias (HE, 3 to 60 mg kg⁻¹, i.p. or 25 to 200 mg kg⁻¹, p.o.) produced significant and graded inhibition of acetic acid-induced abdominal constrictions, with mean ID₅₀ values of 6 and 72 mg kg⁻¹, respectively. The HE (at this same range of doses) also produced dose-related inhibition of both the early and the late phase of formalin-induced licking. The calculated mean ID₅₀ values for the early phase were: > 60 and > 200 mg kg⁻¹, while for the late phase they were 11 and 101 mg kg⁻¹, respectively, by i.p. and p.o. routes. The HE also caused dose-related inhibition of formalin-induced edema formation (P < 0.01). The HE (3 to 60 mg kg⁻¹, i.p. or 50 to 200 mg kg⁻¹, p.o.) produced significant and dose-related inhibition of the neurogenic nociception caused by topical injection of capsaicin, with mean ID₅₀ values of 12 and 71 mg kg⁻¹, respectively. Given orally, the HE (50 to 200 mg kg⁻¹) prevented in a dose-dependent manner, bradykinin (3 $\text{nmol}\text{paw}$) and substance P (10 $\text{nmol}\text{paw}$)-induced hyperalgesia in the rat paw, with mean ED₅₀ values of 122 and 121 mg kg⁻¹, respectively, but was ineffective in the hot-plate model of nociception. The antinociception caused by the HE, in contrast to that of morphine (5 mg kg⁻¹, s.c.), was not reversed by naloxone (5 mg kg⁻¹, i.p.) when assessed in the acetic acid writhing test. The HE, at antinociceptive doses, did not affect motor coordination of animals when assessed in the rota-rod model. The xanthone isolated from P. cyparissias, identified as 1,7-dihydroxy-2,3-dimethoxy xanthone (0.3 to 30 mg kg⁻¹, i.p.), produced dose-related inhibition of acetic acid-induced abdominal constriction, with mean ID₅₀ value of 1.5 mg kg⁻¹. These data show that the active principle(s) present in the HE of P. cyparissias, elicited pronounced antinociception when assessed by i.p or p.o. routes, against both inflammatory and neurogenic nociception, and was able to prevent bradykinin and substance P-induced hyperalgesia. Its precise mechanism of action still remains unclear.