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BackgroundPterodon 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 6α, 7β-dihydroxyvouacapan-17β-oate methyl ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive activity of the crude extract.ResultsCompounds 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.kg-1) containing lower concentrations of compounds C1 (11.5%- 34.6 mg. kg-1) and C2 (1.5% - 4.7 mg.kg-1) gave statistically the same effect to the pure compounds when tested separately (C1 = C2 = 300 mg.kg-1) 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.ConclusionThese 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.

O fracionamento biomonitorado do extrato diclorometânico das sementes de Pterodon pubescens Benth forneceu o 6α-acetóxi-7β-hidróxi-vouacapano 1 (inédito), além de quatro diterpenos furânicos (2, 3, 4 e 5). A atividade antiproliferativa dos compostos foi avaliada in vitro contra as linhagens de células tumorais humanas UACC-62 (melanoma), MCF-7 (mama), NCI-H460 (pulmão), OVCAR-03 (ovário), PC-3 (próstata), HT-29 (colon), 786-0 (rim), K562 (leucemia) e NCI-ADR/RES (ovário com fenótipo de resistência a múltiplos fármacos). Os resultados foram expressos em três concentrações efetivas GI 50 (concentração para que ocorra 50% de inibição de crescimento), TGI (concentração que resulta em inibição total de crescimento) e LC 50 (concentração que resulta em 50% de morte celular). A citotoxicidade in vitro foi avaliada também frente a uma linhagem de célula murina normal (3T3). Este é o primeiro relato de atividade anticâncer para os compostos 1, 4 e 5, que apresentaram grande seletividade, dependente da concentração, para PC-3. O composto 1 foi 26 vezes mais potente para inibir 50% do crescimento (GI 50 ) de PC-3, 15 vezes mais citostático (TGI) e 6 vezes menos tóxico (LC 50 ) quando comparado com Doxorrubicina (controle).Activity guided fractionation of Pterodon pubescens Benth. methylene chloride-soluble fraction afforded novel 6α-acetoxi 7β-hydroxy-vouacapan 1 and four known diterpene furans 2, 3, 4, 5. The compounds were evaluated for in vitro cytotoxic activities against human normal cells and tumour cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-H460 (lung, non-small cells), OVCAR-03 (ovarian), PC-3 (prostate), HT-29 (colon), 786-0 (renal), K562 (leukemia) and NCI-ADR/RES (ovarian expressing phenotype multiple drugs resistance). Results were expressed by three concentration dependent parameters GI 50 (concentration that produces 50% growth inhibition), TGI (concentration that produces total growth inhibition or cytostatic effect) and LC 50 (concentration that produces −50% growth, a cytotoxicity parameter). Also, in vitro cytotoxicity was evaluated against 3T3 cell line (mouse embryonic fibroblasts). Antiproliferative properties of compounds 1, 4 and 5 are herein reported for the first time. These compounds showed selectivity in a concentration-dependent way against human PC-3. Compound 1 demonstrated selectivity 26 fold more potent than the positive control, doxorubicin, for PC-3 (prostrate) cell line based on GI 50 values, causing cytostatic effect (TGI value) at a concentration fifteen times less than positive control. Moreover comparison of 50% lethal concentration (LC 50 value) with positive control (doxorubicin) suggested that compound 1 was less toxic.Keywords: Pterodon pubescens, leguminosae, furanoditerpenes, in vitro assay, prostate cell line, cytotoxicity IntoductionThroughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialized drugs hav...

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