RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Duguetia furfuracea (A. St. -Hil.) Saff. (Annonaceae) is commonly known in Brazil as "araticum-seco," and its root is used in folk medicine to treat inflammatory and painful disorders. However, no studies have been performed to evaluate these therapeutic activities. AIM OF THE STUDY: Investigate the chemical composition, anti-inflammatory and antinociceptive effects, and elucidate the possible antinociceptive mechanisms of action from the essential oil of D. furfuracea (EODf) underground stem bark. MATERIALS AND METHODS: Chemical composition was determined by gas chromatography and mass spectrometry (GC/MS). The paw edema induced by LPS, formalin-induced nociception, LPS-induced thermal hyperalgesia and rota-rod tests in vivo were used to evaluate the anti-inflammatory and antinociceptive effects in addition to the alteration on motor coordination. Histological analyses and an immunohistochemistry assay for iNOS were performed on mouse footpads of naive, control, 10â¯mg/kg EODf, and 10â¯mg/kg indomethacin (Ind) groups. The samples were removed at 1, 3, and 6â¯h after subplantar injection of LPS. In addition, the involvement of the adenosinergic, opioidergic, serotonergic, and cholinergic systems were investigated, in order to elucidate possible antinociceptive mechanisms. RESULTS: Twenty-four volatile constituents were detected and identified. (E)-asarone (21.9%), bicyclogermacrene (16.7%), 2,4,5-trimethoxystyrene (16.1%), α-gurjunene (15%), cyperene (7.8%), and (E)-caryophyllene (4.6%) were major compounds found in EODf. Oral treatment (p.o.) with EODf (1, 3, and 10â¯mg/kg) significantly inhibited the paw edema induced by LPS. At 10â¯mg/kg EODf promoted inhibition of tumor necrosis factor alpha (TNF-α) production, recruitment of polymorphonuclear (PMN) leukocytes and inducible nitric oxide synthase (iNOS) expression in paw tissue. EODf (10 and 30â¯mg/kg, p.o.) also reduced licking time in both phases of the formalin test and it had a significant effect on the LPS-induced thermal hyperalgesia model. The administration of caffeine (Caf) and naloxone (Nal) reversed the antinociceptive activity of EODf, in the first phase of the formalin test and in the LPS-induced thermal hyperalgesia model. Moreover, Nal was also able to abolish the antinociception caused by EODf, in the second phase of formalin test. In the rota-rod test, EODf-treated animals did not show any alteration of motor coordination. CONCLUSIONS: Our findings indicate that EODf underground stem bark produces anti-inflammatory and both central and peripheral antinociceptive effects. Furthermore, the antinociceptive activity of EODf underground stem bark is possibly mediated by adenosinergic and opioidergic pathways, and its properties do not induce effects on motor coordination. These results support the use of the folk medicine, D. furfuracea root, to treat inflammation and painful conditions.
Assuntos
Analgésicos , Annonaceae , Anti-Inflamatórios , Óleos Voláteis , Analgésicos/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Annonaceae/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Edema/imunologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Óxido Nítrico Sintase Tipo II/imunologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Dor/tratamento farmacológico , Medição da Dor , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Raízes de Plantas/química , Antagonistas de Receptores Purinérgicos P1/farmacologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Recent findings have demonstrated new therapeutic functions of cardiotonic steroids, a process that is termed drug repositioning. Despite the confirmed anti-inflammatory effects of cardiotonic steroids, their clinical use has been discouraged due to toxicity related to inhibition of the Na+/K+ ATPase. A novel synthetic compound derived from digoxin, 21benzylidene digoxin (21BD), does not inhibit this enzyme. Herein, we evaluated the anti-inflammatory and antinociceptive effects and acute toxicity of 21BD. Murine (Swiss mice) models of paw oedema induced by carrageenan, acetic acid-induced abdominal writhing, and formalin and acute toxicity tests were used. Oral administration of 21BD (0.3â¯mg/kg) showed a significant and prolonged inhibition of paw oedema. Histological analysis demonstrated a reduction in inflammatory cells and expression of inducible nitric oxide synthase (iNOS) in footpads 6â¯h after administration of carrageenan. 21BD (0.3â¯mg/kg) also reduced the levels of tumour necrosis factor (TNF)-α 2 and 4â¯h after carrageenan. 21BD demonstrated antinociceptive activity, inhibiting abdominal writhes at all tested doses. However, in the formalin test, 21BD did not present antinociceptive activity. In the acute toxicity test, 21BD did not cause symptoms of toxicity or mortality. The present study demonstrated, for the first time, that 21BD is safe and exhibits a marked anti-inflammatory activity in acute local inflammation. This effect might be a consequence of its ability to inhibit the release of the PMN leucocyte-derived mediators, including TNF-α, and iNOS expression as well as its inhibitory effect on oedema and PMN leucocyte infiltration.