Anti-hyperalgesic properties of the extract and of the main sesquiterpene polygodial isolated from the barks of Drymis winteri (Winteraceae)

This study analyses the anti-hyperalgesic properties of the hydroalcoholic extract (HE) and the sesquiterpene polygodial isolated from the barks of Drymis winteri (Winteraceae). The HE (10 to 60 mg kg(-1), i.p. or 100 to 600 mg kg(-1), p.o.), 4 h prior, produced significant inhibition of abdominal constrictions caused by i.p. injection of acetic acid, kaolin and zymosan in mice. The mean ID50s were: 21.4, 33.7 and 36.6 mg kg(-1); 173.0, 123.0 and 366.0 mg kg(-1), by i.p. and by oral route, respectively. This effect lasted for up to 8 h. The HE at the same range of doses produced dose-related inhibition of both phases of the formalin-induced licking. The calculated mean ID50s values for the early phase were: 26.1 and 43.0 mg kg(-1), while for the late phase they were 7.3 and 72.7 mg kg(-1), respectively, when given by i.p. and by oral route. The HE (10 to 60 mg kg(-1), i.p. or 25 to 200 mg kg(-1), p.o.), 4 h prior, produced significant inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 18.0 and 68.0 mg kg(-1), respectively. The HE (3 to 100 mg kg(-1), p.o., 1 h) inhibited in a graded manner, the hyperalgesia induced by bradykinin (3 nmol/paw) or substance P (10 nmol/paw) in rat paw, with mean ED50 values of 54.5 and 53.7 mg kg(-1), respectively. However, the HE did not affect the hyperalgesia induced by carrageenan or PGE2. When assessed in the hot-plate test, the HE (200 mg kg(-1), p.o.) was inactive. Naloxone (1 mg kg(-1), i.p.) significantly reversed the antinociceptive effects caused by either morphine (5 mg kg(-1), s.c.) or by HE (60 mg kg(-1), i.p.). Polygodial (0.1 to 10 mg kg(-1), i.p.) produced significant inhibition of acetic acid, kaolin and zymosan-induced writhing in mice, being about 14 to 27-fold more potent than the HE at the ID50 level. Together these data provide support for a long-lasting anti-hyperalgesic property for the active principle(s) present in the barks of D. winteri when assessed in several models of inflammatory or neurogenic pain. Its actions involve, at least in part, an interaction with opioid pathway through a naloxone-sensitive mechanism, seeming not to be related with a non-specific peripheral or central depressant actions. Finally, the sesquiterpene polygodial isolated from this plant, appears to be mainly responsible for the anti-hyperalgesic properties of the extract.