Pterodon pubescens and Cordia verbenacea association promotes a synergistic response in antinociceptive model and improves the anti-inflammatory results in animal models

Abstract

This study evaluated the pharmacological effect of the association of crude extract from the fruits of Pterodon pubescens (Pp) with the essential oil of Cordia verbenacea (Cv) in antinociception and anti-inflammatory experimental models. The effective doses of each extract and the combinations used in the associations of extracts were defined by acetic acid-induced writhing test. The separate extracts were also evaluated on formalin test. Interaction between extracts was assessed by isobologram method. The effects of different concentrations of associations (A_50, A₁₀₀ and A₂₀₀) were evaluated on formalin test, tail flick and hot plate. The anti-inflammatory activity was evaluated in paw edema induced by carrageenan and PGE2, carrageenan-induced peritonitis and mechanical allodynia induced by Complete Freund's Adjuvant (CFA). The associations were markedly synergistic, as assessed using isobolographic analyses. On formalin and on acetic acid-induced writhing tests, associations demonstrated greater efficacy when compared to extracts separately. In paw edema models, significant reductions of edema were observed. On mechanical allodynia induced by CFA, associations were effective at acute phase with pronounced effect at chronic phase. The associations were not effective in hot plate, tail flick and carrageenan-induced peritonitis tests. Phytochemical analysis by HPLC-DAD and FID showed important concentrations of α-Humulene, trans-Caryophyllene, geranylgeraniol, isomers 6α-hydroxy-7β-acetoxy-vouacapan-17βoate methyl ester and 6α-acetoxy-7β-hydroxy-vouacapan-17β-oate methyl ester (compounds m/z 404) and 6α,7β-dihydroxyvouacapan-17β-oate methyl ester (m/z 362). These findings demonstrate that the associations promote synergistic antinociceptive effect and important anti-inflammatory activities, especially on chronic inflammation conditions, at lower doses than the separate crude extracts, without demonstrating side effects, probably acting in different pharmacological receptors. The inhibition of inflammation suggests a relationship with inflammatory mediators and PGE₂ pathway and might be exploited to achieve greater anti-inflammatory efficacy, being considered as a potential phytotherapy.

Keywords: Anti-inflammatory; Antinociceptive; Cordia verbenacea; Natural products; Pterodon pubescens; Synergism.