RESUMEN
Campomanesia xanthocarpa (Myrtaceae) is used in Brazilian traditional medicine against fever, diabetes, hypercholesteremic, obesity, and urinary diseases. In the present study, the compounds 2',6'-dihydroxy-3'-methyl-4'-metoxychalcone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone were identified for the first time in leaves of the C. xanthocarpa. These compounds and the hydroethanolic extract (HECX) significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. No toxicity was detected by HECX in an acute toxicity test.
Asunto(s)
Antiinflamatorios/farmacología , Chalconas/farmacología , Myrtaceae/química , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/uso terapéutico , Brasil , Movimiento Celular/efectos de los fármacos , Chalconas/aislamiento & purificación , Chalconas/uso terapéutico , Chalconas/toxicidad , Edema/tratamiento farmacológico , Leucocitos/citología , Medicina Tradicional/métodos , Ratones , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Cavidad Pleural/metabolismo , Proteínas/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine. AIM OF THE STUDY: This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models. MATERIALS AND METHODS: Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg). RESULTS: Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test. CONCLUSION: The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The amides obtained seemed to be the active component(s) present in the EEPA because they proved to be anti-nociceptive and anti-hyperalgesic in models of acute pain. Considering that few drugs are currently available for the treatment of chronic pain, especially neuropathic pain, the present results may have clinical relevance and open new possibilities for the development of new anti-hyperalgesic and anti-arthritic agents from P. amalago.
Asunto(s)
Amidas/farmacología , Analgésicos/farmacología , Artritis Experimental/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Piper/química , Extractos Vegetales/farmacología , Amidas/uso terapéutico , Analgésicos/uso terapéutico , Animales , Antidepresivos/farmacología , Frío , Edema/inducido químicamente , Edema/prevención & control , Ratones , Actividad Motora/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Ratas , Ratas Wistar , Neuropatía Ciática/tratamiento farmacológico , Neuropatía Ciática/psicología , Natación/psicologíaRESUMEN
This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity.