RESUMO
Artemisia annua L., known for antimalarial activity, has demonstrated evidence of anti-inflammatory potential. Previously our research group reported the anti-inflammatory and antinociceptive effect of a sesquiterpene lactone-enriched fraction (Lac-FR) obtained from plant, containing artemisinin and deoxyartemisinin. Both the isolated compounds and Lac-FR evaluated on experimental animal models, in the formalin test showed that deoxyartemisinin reduced both neurogenic pain (56.55â¯%) and inflammatory pain (45.43â¯%). These findings were superior to the effect of artemisinin (reduction of 28.66â¯% and 33.35â¯%, respectively). In the tail flick test, the antinociceptive effect reported as a percentage of the maximum possible effect (%MPE), deoxyartemisinin showed a lower antinociceptive effect (41.57â¯%) compared to morphine (75.94â¯%) in 0.5â¯h. After 1.5â¯h, the MPE of deoxyartemisinin (87.99â¯%) exceeded the effect of morphine (47.55â¯%), without reversal with naloxone. The MPE of artemisinin (23.3â¯%) observed after 2â¯h was lower than deoxiartemisinin, without reversal with the opioid antagonist. Lac-FR and artemisinin demonstrated reductions in ear edema of 43.37â¯% and 48.19â¯%, respectively, higher than the effect of deoxyartemisinin (33.64â¯%). Artemisinin reduced tumor necrosis factor alpha (TNF-α) (76.96â¯%) more selectively when compared to interleukin-1beta (IL-1ß) (48.23â¯%) and interleukin-6 (IL-6) (44.49â¯%). Lac-FR showed greater selectivity in IL-6 reduction (56.49â¯%) in relationship to TNF-α (46.71â¯%) and IL-1ß (45.12â¯%), whereas deoxyartemisinin selectively reduced TNF-α (37.37â¯%). The results of our study indicate that the lactones isolated did not have relationship with the opioid system. Deoxyartemisinin showed a higher antinociceptive potential than artemisinin. Whereas, artemisinin showed a higher reduction of inflammation and mediators, with a better anti-inflammatory activity outcome.
Assuntos
Analgésicos , Anti-Inflamatórios , Artemisia annua , Artemisininas , Modelos Animais de Doenças , Artemisininas/farmacologia , Artemisininas/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Artemisia annua/química , Masculino , Analgésicos/farmacologia , Analgésicos/isolamento & purificação , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Inflamação/tratamento farmacológico , Inflamação/patologia , Dor/tratamento farmacológicoRESUMO
Purpose: The prevalence of head lice in poor rural communities and urban slums is estimated to be between 28% and 43% in Brazil, respectively. Children are among the most affected, often in clusters within schools. We launched a program intending to tackle the social stigma associated with head lice using scientific information and a local traditional remedy as a way to lower the prevalence of head lice in a low-resource community. Methods: A program involving the entire school community and the teachers addressed how to treat head lice and avoid new infestations. An affordable solution widely used in traditional Brazilian medicine was provided for the ones infested. Evaluation of the outcome was based on direct observation and was designed as a satisfaction survey. The study complied with the criteria for Standards for Reporting Qualitative Research (SRQR). Results: Two hundred and eighty participants, including parents and siblings of the school children, took part in the program. Among them, 24% (N=67) had head lice, with girls representing 85% of cases; 74.7% of participants infested with head lice were between 4 and 10 years old; 55.2% (N=37) of participants infested showed no signs of nits or adult lice after the program. Conclusions: This experience suggests that the use of playful activities associated with a well-known and accessible local product to treat head lice in low-income families gathered a high degree of community adherence and may be an important tool in overcoming health inequalities.
RESUMO
The present study aimed to further investigate the anti-inflammatory activity of (E)-N-(4-bromophenyl)-2-(thiophen-2-ylmethylene)-thiosemicarbazone (BTTSC) as well as its antinociceptive effects. The anti-inflammatory activity was assessed using the model of ear edema induced by croton oil-induced and also evaluated in models of paw edema carrageenan-induced and by compound 48/80. Evaluation of the antinociceptive effect was performed through formalin test. In the nociception test induced by formalin the BTTSC showed activity in both phases of the pain, highlighting inflammatory pain, where it was able to reduce the time to paw lick 62.3, 84.30 and 100% at doses of 30, 100 and 300mgkg(-1). The anti-inflammatory activity was performed ear edema induced by croton oil, where none of the doses tested was capable of significantly regress edema. The paw edema carrageenan-induced showed activity compound, where the edema was reduced by 81.9 and 83.2% in the first two times of the experiment at the highest dose used. The paw edema assay induced by compound 48/80, showed that BTTSC after 15min of the inoculum phlogistic agent showed significant reduction of edema with values of 56.53% at a dose of 30mgkg(-1). Our results suggesting this compound exerts its antinociception effects connected with peripheral mechanisms. Furthermore, the compound was able to act in two phases of inflammation carrageenan-induced, highlighting the initial phase. This suggests an action on the early mediators of inflammation. The paw edema assay induced by compound 48/80 confirmed our hypothesis indicating action of the compound via histamine.
Assuntos
Anti-Inflamatórios/farmacologia , Tiofenos/farmacologia , Tiossemicarbazonas/farmacologia , Animais , Anti-Inflamatórios/química , Carragenina , Edema/patologia , Camundongos Endogâmicos BALB C , Nociceptividade/efeitos dos fármacos , Tiofenos/química , Tiossemicarbazonas/químicaRESUMO
UNLABELLED: Antileishmanial in vitro tests, as well as Ames and micronucleus assays were performed with a concentrated ethanolic extract of Physalis angulata (EEPA) RESULTS: EEPA did not present mutagenic effect in Salmonella typhimurium strains at concentration reaching 3000 µg/plate and did not induce mutagenic effects after two oral administrations with a 24h interval at a dose level of 2000 mg/kg. EEPA presented antileishmanial activity and presented an IC50 value of 5.35 ± 2.50 µg/mL and 4.50 ± 1.17 µg/mL against Leishmania amazonensis and Leishmania braziliensis promastigotes, respectively. In the cytotoxicity test against macrophages, the EEPA had a LC50 of 6.14 ± 0.59 µg/mL. Importantly, the IC50 against L. amazonensis intracellular amastigotes was 1.23 ± 0.11 µg/mL. CONCLUSION: EEPA extract is non-mutagenic and presented a promising pharmacological effect against Leishmania parasites.
Assuntos
Antiprotozoários , Leishmania/efeitos dos fármacos , Mutagênicos , Physalis/química , Extratos Vegetais/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Etanol , Feminino , Leishmania braziliensis/efeitos dos fármacos , Leishmania mexicana/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos CBA , Testes para Micronúcleos , Testes de Mutagenicidade , Caules de Planta/química , Solventes , Espectrofotometria UltravioletaRESUMO
The currently used treatments for leishmaniasis, a neglected parasitic disease, are associated with several side effects, high cost and resistance of the Leishmania parasites. Here we evaluated in vitro and in vivo the antileishmanial activity of five antimalarial drugs against Leishmania amazonensis. Mefloquine was effective against promastigotes in axenic cultures and showed an IC50 (concentration giving half-maximal inhibition) value of 8.4±0.7 µM. In addition, mefloquine, chloroquine and hydroxychloroquine were active against intracellular amastigotes in macrophage-infected cultures, presenting IC50 values of 1.56±0.19 µM, 0.78±0.08 µM and 0.67±0.12 µM, respectively. The ultrastructural analysis of chloroquine- or mefloquine-treated amastigotes showed an accumulation of multivesicular bodies in the cytoplasm of the parasite, suggesting endocytic pathway impairment, in addition to the formation of myelin-like figures and enlargement of the Golgi cisternae. CBA mice were infected with L. amazonensis in the ear dermis, and treated by oral and/or topical routes with chloroquine and mefloquine. Treatment of L. amazonensis-infected mice with chloroquine by the oral route reduced lesion size, which was associated with a decrease in the number of parasites in the ear, as well as the parasite burden in the draining lymph nodes. In contrast, mefloquine administration by both routes decreased the lesion size in infected mice without causing a reduction in parasite burden. Our results revealed a promising antileishmanial effect of chloroquine and suggest its use in cutaneous leishmaniasis treatment.
Assuntos
Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Animais , Feminino , Concentração Inibidora 50 , Leishmaniose Cutânea/parasitologia , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBARESUMO
Rose-oxide is a fragrance found in roses and rose oil. There are no reports about the pharmacological activity of this molecule. The present study was undertaken to evaluate whether rose-oxide (RO) has anti-inflammatory properties and to investigate possible mechanisms involved with its effects. The anti-inflammatory activity of RO was first suggested by the formalin test in mice, an inflammatory pain model, because intraperitoneal (i.p.) administration of RO (50 and 100mg/kg) inhibited only the late phase of this test. To further investigate the anti-inflammatory properties of RO, the complete Freund's adjuvant (CFA)- and carrageenan-induced paw inflammation models were used. Pre-treatment with RO (50 and 100mg/kg) significantly reduced paw edema at 4, 6 and 24h after the CFA injection. In addition, RO (100mg/kg) reduced the IL-1ß, but not TNF-α, local production induced by CFA. Administration of RO (25-100mg/kg) decreased the paw edema induced by carrageenan in rats, which was more evident at 3 and 4h after induction. In addition, neutrophil migration to the hind paw was measured by MPO assay after the carrageenan injection. The MPO activity was significantly inhibited by RO at 25-100mg/kg, 4h after stimulus. In another experimental set, administration of RO (25-100mg/kg) significantly reduced the leukocyte migration in the carrageenan-induced peritonitis model in mice. The results described here are the first report of pharmacological properties of RO and strongly suggest that RO possesses anti-inflammatory activity related to its ability to inhibit the IL-1ß production and the leukocyte migration.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Monoterpenos/farmacologia , Monoterpenos Acíclicos , Animais , Anti-Inflamatórios não Esteroides/química , Ensaios de Migração de Leucócitos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Camundongos , Monoterpenos/química , Ratos , Ratos WistarRESUMO
Bergenin (1) is a C-glucoside of 4-O-methylgallic acid with known antiarthritic activity attributed to modulation of cytokine production. The present study was undertaken to evaluate whether 1 has antinociceptive properties in models of inflammatory pain and to investigate its possible mechanisms of action. Pretreatment with 1 (12.5-100 mg/kg, ip) produced a dose-related inhibition of acetic acid-induced writhing in mice. Furthermore, treatment with 1 (50 and 100 mg/kg) inhibited both the early and late phases in a formalin test. In addition, 1 (50 and 100 mg/kg, ip) inhibited mechanical hyperalgesia, edema, and paw production of hyperalgesic cytokines (TNF-α and IL-1ß) induced by complete Freund's adjuvant. However, the local production of IL-10, an anti-inflammatory cytokine, was not altered by 1 (100 mg/kg, ip). Treatment with 1 produced a similar profile of antinociception in wild-type and IL-10-deficient mice. Mice treated with 1 did not show any motor performance alterations or apparent systemic toxicity. The results presented herein demonstrate that bergenin has consistent antinociceptive and anti-inflammatory properties, acting by the inhibition of IL-1ß and TNF-α production, and suggest its potential for the control of inflammatory pain.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Benzopiranos/farmacologia , Dor/tratamento farmacológico , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/química , Benzopiranos/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Interleucina-10/antagonistas & inibidores , Interleucina-10/biossíntese , Interleucina-10/genética , Masculino , Camundongos , Dor/induzido quimicamente , Medição da Dor , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossínteseRESUMO
7-Hydroxycoumarin (umbelliferone, 1), the main metabolite of coumarin, has been reported to produce potent antinociceptive effects in animal models of pain. However, the biochemical events involved in antinociception mediated by 1 are currently not well understood. In the present study, the mechanisms by which 1 exerts its pharmacological actions were investigated. Acute pretreatment of mice with 1 produced a long-lasting antinociceptive effect against complete Freund's adjuvant (CFA)-induced hyperalgesia. The subchronic administration of 1 inhibited CFA-induced hyperalgesia and paw edema, while it did not cause any apparent toxicity. Another set of experiments showed that 1 inhibited carrageenan-induced mechanical hyperalgesia, but not mechanical hyperalgesia induced by prostaglandin E(2) (PGE(2)), suggesting that it acts upstream of PGE(2.) Treatment with 1 was able to prevent the plantar tissue neutrophil influx induced by local inflammatory stimuli. In addition, 1 exhibited inhibitory effects on the release of hyperalgesic cytokines (TNF-α and IL-1ß) and the production of PGE(2), a directly acting hyperalgesic mediator. The present results suggest that the antinociceptive effect of 1 is correlated with the inhibition of neutrophil migration, cytokine release, and PGE(2) production and are supportive of the further investigation of the therapeutic potential of 1 to control inflammatory pain.
Assuntos
Analgésicos/farmacologia , Dor/tratamento farmacológico , Umbeliferonas/farmacologia , Analgésicos/química , Analgésicos/metabolismo , Analgésicos/uso terapêutico , Animais , Brasil , Dinoprostona/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Adjuvante de Freund/farmacologia , Camundongos , Modelos Animais , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Dor/induzido quimicamente , Medição da Dor , Fator de Necrose Tumoral alfa/farmacologia , Umbeliferonas/química , Umbeliferonas/uso terapêuticoRESUMO
AIM OF STUDY: Adiantum, one of the most widely distributed genera of the family Pteridaceae, is employed in folk medicine worldwide. Adiantum latifolium Lam. has been used in Latin American traditional medicine as anxiolytic, analgesic and antiinflammatory. The present study investigates the antinociceptive and antiinflammatory properties of the methanolic extract of Adiantum latifolium (MEA) in animal models of pain and inflammation to confirm its medicinal use. MATERIAL AND METHODS: The antinociceptive and antiinflammatory activities of MEA were evaluated using the writhing, formalin, and tail-flick tests, carrageenan-induced paw edema and arachidonic acid-induced ear edema. Mice motor performance was evaluated in the rota rod test and the acute toxicity evaluated over 14 days. RESULTS: Intraperitoneal (1-100mg/kg) or oral (100-400mg/kg) administration of MEA produced a dose-related inhibition of acetic acid-induced writhing in mouse. Furthermore, treatment with MEA (100mg/kg) inhibited both the early and late phases of formalin-induced hypernociception. In contrast, MEA (100mg/kg/IP) did not prevent the thermal nociception in the tail-flick test. In addition, MEA (100 and 200mg/kg/IP) inhibited important events related to the inflammatory response induced by carrageenan or arachidonic acid, namely local edema and increase in tissue interleukin-1ß levels. MEA (300mg/kg/IP)-treated mice did not show any motor performance alterations. Over the study period of 14 days, there were no deaths or toxic signs recorded in the group of mice given 1000mg/kg of MEA. CONCLUSION: The results demonstrate that Adiantum latifolium has antinociceptive and antiinflammatory activities, acting through the inhibition of IL-1ß production.
Assuntos
Adiantum , Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Interleucina-1beta/antagonistas & inibidores , Dor/tratamento farmacológico , Fitoterapia , Ácido Acético , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Ácido Araquidônico , Comportamento Animal/efeitos dos fármacos , Carragenina , Relação Dose-Resposta a Droga , Orelha , Edema/tratamento farmacológico , Edema/metabolismo , Formaldeído , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Dor/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
AIM OF STUDY: Blechnum occidentale L. is a terrestrial fern that ranges from the United States to South America, and is employed in Brazilian folk medicine. In the present study we investigated the antinociceptive and antiinflammatory activities of the methanolic extract of Blechnum occidentale L. (MEB) in animal models of pain and inflammation to support its medicinal use in treatment of inflammatory and pulmonary diseases, urinary infections and liver diseases. MATERIALS AND METHODS: The antinociceptive activity of MEB was evaluated using the writhing, formalin, and tail flick tests. The antiinflammatory activity of MEB was evaluated in carrageenan-induced paw oedema and neutrophil migration. In order to discard possible non-specific muscle relaxant or sedative effects of MEB, mice motor performance was evaluated in the rota rod test and its toxicity evaluated over 14 days. RESULTS: Intraperitoneal (IP) administration of MEB (0.01-100mg/kg) produced a dose-related antinociception on acetic acid-induced writhing in mice. Oral administration of MEB, at a different range of doses (100-400 mg/kg), also produced significant antinociceptive effect on the writhing test. Furthermore, treatment with MEB (100 and 200 mg/kg IP) inhibited significantly both the early and late phases of formalin-induced hypernociception in rats. In contrast, treatment with MEB (100 and 200 mg/kg IP) did not prevent the thermal nociception in the tail flick test. The IP administration of MEB (100 and 300 mg/kg) significantly reduced the paw oedema induced by carrageenan. Moreover, systemic treatment with MEB (11-300 mg/kg) reduced the neutrophil migration in the carrageenan-induced migration to the peritoneal cavity. In the rota rod test, MEB-treated mice did not show any significant motor performance alterations with the dose of 300 mg/kg. In addition, over the study duration of 14 days, there were no deaths or toxic signs recorded in the mice given 100 or 1000 mg/kg of MEB. CONCLUSION: The results described here are the first report of pharmacological studies of Blechnum occidentale L. and indicate that this plant has antinociceptive and antiinflammatory activities which support its folk medicine use.