RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has been used as a folk medicine for centuries around the world due to its wide spectrum of biological activities. The red propolis, a new Brazilian variety of this apimaterial, has presented an unusual chemical composition, including isoflavones such as formononetin and biochanin A. Since both the green and red varieties of propolis are traditionally used as medicine and commercialized with no label differentiation, the study of the activities of red propolis extract has become important in order to clarify whether this product has the same activities as commercial ones. In this work, we demonstrated the potential action of the hydroalcoholic extract of red propolis (HERP) and its biomarker, formononetin, as antinociceptive and anti-inflammatory drugs on experimental models. MATERIALS AND METHODS: The HERP was chemically characterised by HPLC/DAD analyses. The biological activities of the HERP (3, 10, and 30mg/kg) and formononetin (10mg/kg) were evaluated using the antinociceptive (acetic acid, formalin, and glutamate injections) and anti-inflammatory (carrageenan-induced hindpaw oedema and peritonitis) models in mice after oral administration. The open field test was also performed. RESULTS: Formononetin, one of the main biomarker of red propolis, was identified in the HERP (21.62mg/g). Pretreatment with the HERP (10 and 30mg/kg) and formononetin (10mg/kg) produced reduction (P<0.001) in the number of abdominal writhes, but the HERP was more effective (P<0.001) than formononetin. In the formalin test, all HERP doses (3, 10, and 30mg/kg, P<0.001) inhibited the late phase (inflammatory pain) of formalin-induced licking, but the inhibition of neurogenic pain was observed only when the higher doses (10 and 30mg/kg; P<0.05) were used. Formononetin caused inhibition (P<0.001) only in the second phase of formalin-induced nociception similarly at all HERP doses in the same phase of the test. The responses in glutamate-induced model presented crescent inhibition (P<0.05) with 10 and 30mg/kg of HERP. Also, formononetin inhibited (P<0.001) the nociception induced by glutamate similarly to 30mg/kg of HERP. There were no significant differences in the open field test after HERP administration, but formononetin decrease the spontaneous motor behaviour. Regarding the anti-inflammatory assessment, the HERP (10 and 30mg/kg, P<0.05) and formononetin (P<0.001) treatments caused a significant inhibition of the oedema response. All doses of HERP (3, 10, and 30mg/kg, P<0.05) and formononetin (P<0.001) also inhibited the carrageenan-induced leukocyte migration. In both cases, the results for the HERP at 30mg/kg and formononetin were similar. CONCLUSIONS: The HERP and formononetin presented significant anti-inflammatory activity. Moreover, the HERP presented antinociceptive action on inflammatory and neurogenic pain without motor side effects, possibly due to the action of other constituents present in the extract. These results, together, support the popular usage of this natural product.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Dor/tratamento farmacológico , Peritonite/tratamento farmacológico , Própole/química , Ácido Acético , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Brasil , Carragenina , Movimento Celular/efeitos dos fármacos , Edema/induzido quimicamente , Edema/imunologia , Feminino , Formaldeído , Ácido Glutâmico , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Masculino , Camundongos , Dor/induzido quimicamente , Peritonite/induzido quimicamente , Peritonite/imunologia , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a bee product widely used in folk medicine due to its numerous pharmacological properties. However, samples from different regions can differ in chemical composition, effectiveness, and side effects. Despite the widespread use of Brazilian red propolis, which is an isoflavone-rich variety, its toxicity has not been carefully studied. AIMS OF THE STUDY: To assess the acute and sub-acute toxicity of the hydroethanolic extract of red propolis (HERP) administered orally to rats. MATERIALS AND METHODS: HERP for the acute (300mg/kg) and sub-acute (10, 100 and 200mg/kg) toxicity studies was administered orally to rats according to OECD Guidelines 420 and 407, respectively. Clinical signs were identified, and hematological and biochemical analyses were performed. Water and food uptake as well as body and organ weights of animals were recorded. RESULTS AND CONCLUSIONS: The acute study revealed no lethal effects at 300mg/kg of HERP, but toxic signs were observed, as HERP had an LD50 of more than 300mg/kg, indicating a warning. The most toxic signals in sub-acute studies were observed in males at a dose of 200mg/kg HERP. These results suggest estrogen-like activity, possibly from the isoflavones in HERP.
Assuntos
Abelhas , Isoflavonas/toxicidade , Própole/toxicidade , Administração Oral , Animais , Brasil , Relação Dose-Resposta a Droga , Feminino , Isoflavonas/isolamento & purificação , Dose Letal Mediana , Masculino , Medicina Tradicional , Tamanho do Órgão/efeitos dos fármacos , Própole/administração & dosagem , Ratos , Ratos Wistar , Fatores Sexuais , Testes de Toxicidade Aguda , Testes de Toxicidade SubagudaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hydroalcoholic solutions of propolis, a resinous product produced by bees, have been currently employed in improving the cicatricial repair. Biological activity of propolis might be related to its antimicrobial, anti-inflammatory and immunomudalatory properties. AIM OF THIS STUDY: Investigate the suitability of the collagen-based films containing hydroalcoholic extracts of two different varieties of Brazilian propolis (green and red ones) on the dermal burn healing in rodent model. MATERIALS AND METHODS: The hydroalcoholic extracts of red propolis (RP) or Green propolis (GP) were incorporated into collagen-based dressing films (COL). Burn wounds were performed in the dorsum of Wistar rats and dressing with COL, COL+GPa (0.5%), COL+GPb (1,0%) or COL+RP (0.5%). A control group (CTR) was performed keeping the wound undressed. The histological analyses were carried out after 3, 7, 14, 21 and 30 days for histological assessment of the inflammatory response, epithelization rates (ER), myofibroblastic count (MC) and collagenization pattern. RESULTS: GPa, GPb and RP provided significant decrease of the inflammatory severity, improved the ER in GPa in 7 (p=0.000), 14 (p=0.000), 21 (p=0.005) and 30 days (p=0.015), and induced earlier replacement of type-III for type-I collagen (p<0.05) than COL and CTR. In all the groups, the MC increased progressively from 3 to 14 days, and then started to decrease slowly until 21 days. Although no significant difference was observed among the groups in 3, 7 and 30 days, the MC was significantly increased in RP in 14 (p=0.0001) and 21 days (p=0.04), as well as grosser interlacement of the collagen bundles compared with the other groups. CONCLUSION: The incorporation of hydroalcoholic extracts of Brazilian propolis improved the biological events associated to burn healing without toxic effects, but the red variety provided the best results. Therefore, these collagen-based containing natural apicultural products films may be considered a promising new dressing for wound occlusion and tissue repairing.