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| Author(s): |
Rosanna Tarkany Basting
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2018-01-31 |
| Examining board members: |
Mary Ann Foglio;
Jörg Kobarg;
Rodrigo Ramos Catharino;
Angela Maria Carneiro Araújo;
Dulce Helena Siqueira Silva
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| Advisor: | Mary Ann Foglio |
| Abstract | |
The species Pterodon pubescens Benth. (sucupira) and Cordia verbenacea DC are plants popurlaly used by due to their analgesic, anti-inflammatory and antirheumatic properties. This work aimed to evaluate the pharmacological effect of the association of the crude extract of the fruits of Pterodon pubescens Benth. (Pp) with the essential oil of Cordia verbenacea DC (Cv) in in vivo experimental models of nociception and inflammation. In addition, the extracts, the association of the extracts and two of the main active compounds, ?-Humulene and the position isomers 6?- hydroxy-7?-acetoxy-vouacapan-17?-oate methyl ester and 6?-acetoxy-7?-hydroxyvouacapan-17?-oate methyl ester (m/z 404) were evaluated in the migration and proliferation of human immortalized keratinocytes (HaCaT) and in anti-inflammatory activity (VEGF and IL-8) in vitro in cells stimulated by tumor necrosis factor alpha (TNF-?). The oral administration of the associations did not cause changes in the behavioral parameters of the animals, in the weight gain in the acute toxicity tests and in the open field test. The interaction between the extracts association evaluated by the isobologram method was classified as an interaction of synergism. In the formalin test, the associations were only significant in the inflammatory phase. In the hot plate and tail withdrawal models, the associations did not show significant efficacy against nociception due to thermal stimulation. In the paw edema model induced by carrageenan, the associations showed a significant reduction of edema. In the model of paw edema induced by PGE2, the association showed a significant reduction of edema. In the migration of leukocytes into carrageenan-induced peritonitis, the associations did not significantly reduce leukocyte migration. In mechanical allodynia induced by Freund's Complete Adjuvant, the data showed that the associations were effective in the acute phase with a pronounced effect in the chronic phase. The analysis performed by HPLC-DAD and FID showed important determined concentrations of ?-Humulene (0.64% Pp, 1.23% Cv), trans-Cariophilene (4.54% Pp, 4.03% Cv), geranylgeraniol 0.21% Pg, 0.12% Cv) and m / z 404 compounds (14.61% Pg) in / z 362 (6.55% Pg). For in vitro cell migration evaluation, it has been shown that Pp, Cv and the association of both inhibited proliferation and cell migration in vitro. The compound m/z 404 (C1) also showed antiproliferative effect and inhibited cell migration at higher concentrations. Thus, these compounds would have potential use as a local treatment against cutaneous diseases involved in hyperproliferation. ?-Humulene demonstrated activity in cell migration at all concentrations tested. In cells stimulated by TNF-?, Pp and Cv increased the production of VEGF, concentration-dependent. The association at the highest concentration increased VEGF levels, while the lower concentrations had no effect. C1 increased VEGF levels at higher concentrations. ?-Humulene significantly increased VEGF levels at higher concentrations. All samples reduced IL-8 levels in anti-inflammatory activity in vitro. Therefore, we suggest that ?-Humulene may have a dual activity - at higher concentrations, the compound shows an anti-inflammatory and angiogenic effect, while at lower concentrations, it exerts anti-angiogenic activity, inhibiting migration, possibly by preventing secretion of VEGF. Treatment with ?-Humulene may be a potential therapeutic strategy to promote wound healing and to prevent inflammation in a persistent inflammatory condition. The results show that the association of the crude extract of the fruits of Pterodon pubescens Benth. (Pp) with the essential oil of Cordia verbenacea DC (Cv) show a synergistic effect and demonstrate important antinociceptive and anti-inflammatory activities at lower doses than the separated crude extracts, probably acting at different pharmacological receptors, without showing any side effects. However, this synergistic effect was not observed in the in vitro tests (AU) | |
| FAPESP's process: | 15/08600-2 - Pterodon pubescens Benth. and Cordia verbenacea DC: evaluation of synergestic effect in anti-inflammatory activity and studies of mechanisms of action and cell signaling |
| Grantee: | Rosanna Tarkany Basting |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |