Pterodon pubescens Benth: Isobolographic analysis of the Antinociceptive Interaction between enriched fractions of sesquiterpene, geranylgeraniol and voucapan compounds

Pterodon pubescens Benth fruits are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. Several studies have attributed antinociceptive activity of this species to the presence of enriched fractions containing geranylgeraniol and vouacapan compounds. The aim of this study was to evaluate synergistic effect of these fractions. Individual dose-response curves in acetic acid-induced abdominal writing test were measured for the separate fractions determening ED₅₀. All treatments decreased significantly and in a dose dependent manner the writhing behavior with ED₅₀ values of 102,34; 101,96; and 63,83 mg.kg^-1, for sesquiterpene, geranylgeraniol and voucapan fractions, respectively (ANOVA p < 0.05). An isobolographic analysis allowed the characterization of the pharmacological interaction produced by a fixed ratio combination of 3:1, 1:1 and 1:3 of equi-effective doses of these fractions. Theoretical antinociceptive ED50 values of sesquiterpene/vouacapan fraction were 92,71; 83,09 and 73,46 mg.kg^-1, respectively. Experimentally antinociceptive ED₅₀ values were 126,73; 69,96 and 57,91 mg.kg^-1 (ANOVA p < 0.05), respectively. These results showed that: in the 3:1 proportion there is a antagonic interaction for these fractionswhereas with 1:1 and 1:3 proportion there was a synergic interaction. Theoretical antinociceptive ED₅₀ values of geranylgeraniol/vouacapan fractions were (92,43; 82,90 and 73,36 mg.kg-1, respectively) lager than those observed experimentally (68,53; 41,51 and 37,21 mg.kg^-1 (ANOVA p < 0.05), respectively) reporting synergic interaction in this association. Data suggest a synergic action between sesquiterpene and vouacapan fractions. Geranygeraniol and the vouacapan fractions also presented synergistic interactions in the acetic acid-induced abdominal writhing test.