Antinociceptive effect of geranylgeraniol and 6alpha,7beta-dihydroxyvouacapan-17beta-oate methyl ester isolated from Pterodon pubescens Benth

Humberto M Spindola, Leila Servat, Carina Denny, Rodney A F Rodrigues, Marcos N Eberlin, Elaine Cabral, Ilza M O Sousa, Jorge Y Tamashiro, João E Carvalho, Mary A Foglio
BMC Pharmacology 2010, 10: 1

BACKGROUND: Pterodon pubescens Benth seeds 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. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6alpha, 7beta-dihydroxyvouacapan-17beta-oate methyl ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive activity of the crude extract.

RESULTS: Compounds C1 and C2 demonstrated activity against writhing with intraperitoneal (i.p.) and oral (p.o.) routes, capsaicin (i.p. and p.o.), glutamate (i.p.), and in the hot-plate (p.o.) tests, demonstrating their contribution to the antinociceptive activity of crude Pterodon pubescens Benth extracts. The observed activity of compounds C1 and C2 may be related to vanilloid receptors VR1, and/or glutamate peripheral receptors. In hot-plate model, the antinociceptive activity was maintained when naloxone chloride (opioid antagonist) was administered prior to treatment with compounds suggesting that C1 and C2 (p.o.) do not exert their antinociceptive effects in the hot-plate test via opioid receptors. The findings presented herein also suggest that compounds within the crude Pterodon pubescens Benth. extract may exert a synergistic interactive effect, since the crude extract (300 mg x kg-1) containing lower concentrations of compounds C1 (11.5%- 34.6 mg x kg-1) and C2 (1.5% - 4.7 mg x kg-1) gave statistically the same effect to the pure compounds when tested separately (C1 = C2 = 300 in writhing experimental model with p.o. administration. Further studies will be undertaken to establish more specifically the mechanisms of action for compounds C1 and C2. Possible synergistic interactions will be evaluated employing the Isobole method.

CONCLUSION: These results allowed us to establish a relationship between the popular use of Pterodon pubescens seeds for pain relief and the activity of two major compounds isolated from this species which demonstrated antinociceptive activity. Various "in vivo" experimental models corroborate the folk use of this species for different pain and inflammation disorders.

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