RESUMO
Abstract The administration of medications on the skin through transcutaneous routes is a practice that has been used by mankind for millennia. Some studies have been reporting the use of terpenes and natural oils rich in terpenes as an enhancer of cutaneous penetration. Copaiba oil, due to its rich content of terpenes, presents itself as a great choice of penetration enhancer for drugs administered on the skin. In this study, we developed two cream formulations containing 5% of ibuprofen (IBU) and copaiba oil: IBCO5 and IBCO10 with 5% and 10% of copaiba oil respectively. Ex vivo cutaneous penetration/permeation studies of IBU were performed using pig ear skin as biological membrane in the Franz-type diffusion cells. The steady-state flux of IBU samples, IBCO5 (35.72 ± 6.35) and IBCO10 (29.78 ± 2.41) were significantly higher when compared with control without copaiba oil (10.32 ±1.52) and with a commercial product (14.44 ± 2.39). In the penetration analysis, the amount of IBU found in the samples IBCO5 and IBCO10 was markedly higher in the dermis than epidermis. Our results showed that copaiba oil possesses attracting properties in promoting skin penetration and permeation of IBU when added into cream formulations.
Assuntos
Pele , Extratos Vegetais/análise , Ibuprofeno/análise , Fabaceae/efeitos adversos , Terpenos/efeitos adversos , Óleos/análise , Preparações Farmacêuticas/classificaçãoRESUMO
Abstract The Brazilian native species Cestrum intermedium, known as mata-boi, induces hepatotoxicity and death when ingested by cattle. While most studies on this species focus on toxicological features, our study is the first to describe the anatomy and in vitro biological activities of Cestrum intermedium. We investigated adult leaves and stems by histochemistry, described their anatomy, performed physical-chemical analysis, determined in vitro antioxidant and antimicrobial activities, and identified secondary metabolites. A few noteworthy anatomical features were the anomocytic stomata on the abaxial surface and the absence of trichomes, in addition to the circular shaped petiole with two projections on the adaxial surface. Histochemical analysis showed chemical markers such as alkaloids, usually reported as toxic, and terpenoids. Potassium nitrate (ATR-FTIR) and lupeol palmitate (NMR) were detected on the crude stem extract. Thermogravimetric and physical-chemical analysis provided fingerprint parameters for the species. Minimal Inhibitory Concentration (MIC) assay revealed that Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were weakly inhibited by extract samples. Chloroform and ethyl acetate fractions presented high phenolic content, which resulted in in vitro antioxidant activity. These novel features expand the knowledge about this species, considering that previous studies mainly focused on its toxicity. Our study also provided characteristics that may help in avoiding misidentification between Cestrum members, especially when taxonomic keys cannot be employed, as in the absence of flowers and fruits.
Assuntos
Técnicas In Vitro/métodos , Solanaceae/anatomia & histologia , Solanaceae/classificação , Staphylococcus epidermidis , Terpenos/efeitos adversos , Microscopia Eletrônica de Varredura/métodos , Caules de Planta/anatomia & histologia , Folhas de Planta/anatomia & histologiaRESUMO
Systemic lupus erythematosus (SLE) is a multifactorial and autoimmune inflammatory disease with pleomorphic clinical manifestations involving different organs and tissues. The study of different murine models has provided a better understanding of these autoimmune phenomena. Pristane-induced lupus represents a suitable model to study factors that could influence the induction and/or progression of SLE, including genetic factors. The objective of the present study was to evaluate the development and evolution of SLE after vitamin D supplementation in PIL model. Here, we evaluated the effects of vitamin D supplementation in model of pristane-induced SLE in female BALB/c mice. The animals were randomly divided into three groups: control group (CO), pristane-induced lupus group (PIL) and pristane-induced lupus group plus vitamin D (VD). Lupus was induced in PIL and VD groups using pristane. PIL group showed arthritis and kidney injury, characterized by increased proteinuria, glomerular mesangial expansion and inflammation. Moreover, PIL model showed increased levels of IL-6, TNF-α and IFN-γ in serum. We observed that treatment with vitamin D improved arthritis through reduced of incidence and arthritis clinical score and edema, but does not influenced renal injury. Treatment with vitamin D was not able to reduce proteinuria levels, decrease mesangial hypercellularity or IgG and IgM deposition in the kidney. Vitamin D supplementation did not alter IL-6, TNF-α, IL-2 and IL-4, but reduce IFN-γ. These results support that the role of vitamin D may be different depending on acting site, what could explain different responses according clinical phenotype. Therefore, further investigations of vitamin D are needed to explore the supplement dosage, timing, and the molecular basis in SLE.
Assuntos
Artrite , Nefrite Lúpica , Terpenos/efeitos adversos , Vitamina D/farmacologia , Animais , Artrite/induzido quimicamente , Artrite/tratamento farmacológico , Artrite/imunologia , Artrite/patologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Camundongos , Camundongos Endogâmicos BALB C , Terpenos/farmacologiaRESUMO
Mouse lines selected for maximal (AIRmax) or minimal acute inflammatory reaction (AIRmin) were used to characterize the immune response and the influence of genetic background during pristane-induced arthritis (PIA). Susceptible AIRmax mice demonstrated exacerbated cellular profiles during PIA, with intense infiltration of lymphocytes, as well as monocytes/macrophages and neutrophils, producing higher levels of IL-1ß, IFN-γ, TNF-α, IL-10, total IgG3, and chemokines. Resistant AIRmin mice controlled cell activation more efficiently than the AIRmax during arthritis progression. The weight alterations of the spleen and thymus in the course of PIA were observed. Our data suggest that selected AIRmax cellular and genetic immune mechanisms contribute to cartilage damage and arthritis severity, evidencing many targets for therapeutic actions.
Assuntos
Artrite Experimental/imunologia , Citocinas/imunologia , Imunoglobulina G/imunologia , Terpenos/efeitos adversos , Doença Aguda , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/genética , Artrite Experimental/patologia , Citocinas/genética , Imunoglobulina G/genética , Inflamação , Camundongos , Baço/imunologia , Baço/patologia , Terpenos/farmacologia , Timo/imunologia , Timo/patologiaRESUMO
In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment) developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1ß, IL-6, TNF-α e IFN-γ) as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana, provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1ß, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: ß-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol); octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model.
Assuntos
Agave/química , Autoimunidade/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Extratos Vegetais/farmacologia , Terpenos/efeitos adversos , Animais , Autoanticorpos/sangue , Autoanticorpos/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/imunologia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Ten known meroterpenoids and the new meroterpenoid 7 were isolated from the Chilean seaweed Stypopodium flabelliforme as their acetylated derivatives. Furthermore, the known metabolite taondiol has been isolated for the first time from this species. The molecular structure of the new metabolite was determined by spectroscopic methods based on 1D- and 2D-NMR. Isolation of 7 represents a key step toward a better understanding of the biogenesis of this class of meroterpenoids. Among the meroditerpenoids isolated, stypodiol, isoepitaondiol, epitaondiol and sargaol exhibited gastroprotective activity on the HCl/Ethanol-induced gastric lesions model in mice. Regarding the mode of gastroprotective action, the activity of epitaondiol was reversed significantly when animals were pretreated with indomethacin, N-ethylmaleimide and N-nitro-l-arginine methyl ester (L-NAME) suggesting that prostaglandins, sulfhydryl groups and nitric oxide are involved in their mode of gastroprotective action. In the case of sargaol the gastroprotective activity was attenuated with indomethacin and N-ethylmaleimide, which suggests that prostaglandins and sulfhydryl groups are also involved in the mode of action using this model.
Assuntos
Antiulcerosos/isolamento & purificação , Modelos Animais de Doenças , Diterpenos/isolamento & purificação , Descoberta de Drogas , Phaeophyceae/química , Alga Marinha/química , Úlcera Gástrica/prevenção & controle , Acetilação , Animais , Antiulcerosos/efeitos adversos , Antiulcerosos/química , Antiulcerosos/uso terapêutico , Linhagem Celular , Chile , Diterpenos/efeitos adversos , Diterpenos/química , Diterpenos/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Humanos , Camundongos , Estrutura Molecular , Oceano Pacífico , Phaeophyceae/crescimento & desenvolvimento , Polinésia , Substâncias Protetoras/efeitos adversos , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Alga Marinha/crescimento & desenvolvimento , Estereoisomerismo , Terpenos/efeitos adversos , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/uso terapêuticoRESUMO
Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP-MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.
Assuntos
Lúpus Eritematoso Sistêmico/metabolismo , alfa-MSH/metabolismo , Animais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Artrite/tratamento farmacológico , Artrite/etiologia , Artrite/imunologia , Artrite/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/imunologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Receptor Tipo 1 de Melanocortina/metabolismo , Terpenos/efeitos adversos , alfa-MSH/administração & dosagemRESUMO
BACKGROUND: Banana and papaya are among the most important crops in the tropics, with a value amounting to millions of dollars per year. However, these fruits suffer significant losses due to anthracnose, a fungal disease. It is well known that certain seaweed extracts possess antifungal activity, but no published data appear to exist on the practical application of this property. In the present study, five organic Brazilian seaweed extracts were screened for their activity against banana and papaya anthracnose fungi. Furthermore, cytotoxic and mutagenic effects of the extracts were evaluated by the brine shrimp lethality assay and the Allium cepa root-tip mutagenicity test respectively, while their major components were identified by gas chromatography/mass spectrometry. RESULTS: Strong fungus-inhibitory effects of Ochtodes secundiramea and Laurencia dendroidea extracts were observed on both papaya (100 and 98% respectively) and banana (89 and 78% respectively). This impressive activity could be associated with halogenated terpenes, the major components of both extracts. Only Hypnea musciformis extract showed cytotoxic and mutagenic effects. CONCLUSION: The results of this study suggest the potential use of seaweed extracts as a source of antifungal agents with low toxicity to control anthracnose in papaya and banana during storage.
Assuntos
Antifúngicos/farmacologia , Colletotrichum/efeitos dos fármacos , Frutas/microbiologia , Doenças das Plantas/microbiologia , Rodófitas/química , Alga Marinha/química , Terpenos/farmacologia , Animais , Antifúngicos/efeitos adversos , Antifúngicos/análise , Artemia/efeitos dos fármacos , Carica/microbiologia , Dieta , Microbiologia de Alimentos , Humanos , Musa/microbiologia , Mutagênicos , Doenças das Plantas/prevenção & controle , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Rodófitas/efeitos adversos , Terpenos/efeitos adversos , Terpenos/análise , Clima TropicalRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The role of Azadirachta indica (neem) against Chagas disease and its antibiotic and antidiabetic action have been demonstrated in non-pregnant animals. However, the effects of neem on lipid metabolism and oxidative stress during pregnancy remain to be investigated. The objective of this study was to evaluate the effects of Azadirachta indica (neem) on maternal reproductive performance and biochemical parameters in non-diabetic and streptozotocin-induced mild diabetic rats (MD). MATERIALS AND METHODS: Pregnant rats were randomly distributed into six experimental groups: ND=non-treated non-diabetic (n=13); NDOil=non-diabetic treated with 1.2 mL/day neem seed oil (n=12); NDPA=non-diabetic treated with 1.0mg/mL/day azadirachtin (n=12); D=non-treated diabetic (n=13); DOil: diabetic treated with neem seed oil (n=12), and DPA=diabetic treated with azadirachtin, n=13. Treatment with either neem oil (1.2 mL/day) or azadirachtin (1.0mg/mL/day) was orally administered throughout pregnancy. Glucose test tolerance (GTT) was performed at day 17 of pregnancy and used as an inclusion criterion. At term pregnancy, maternal reproductive outcomes, lipid profile and oxidative stress status were assessed. RESULTS: Treatment with neem oil and azadirachtin during pregnancy (1) had no hypoglycemic and anti-hyperglycemic effects on non-diabetic and diabetic rats, respectively; (2) affected OGTT glycemic levels in diabetic rats; (3) increased the proportion of fetuses classified as small for pregnancy age (SPA) in all groups; and (4) did not interfere with the lipid profile in non-diabetic dams. Neem oil reduced the rate of total cholesterol and NEFA in diabetic animals. Both neem oil and azadirachtin increased lipoperoxidation, characterized by increased MDA levels in non-diabetic rats. CONCLUSION: Both neem seed oil and azadirachtin impaired intrauterine development and altered antioxidant/oxidative status during pregnancy.
Assuntos
Azadirachta , Desenvolvimento Fetal/efeitos dos fármacos , Glicerídeos/efeitos adversos , Limoninas/efeitos adversos , Terpenos/efeitos adversos , Animais , Diabetes Mellitus Experimental/metabolismo , Feminino , Reabsorção do Feto , Teste de Tolerância a Glucose , Metabolismo dos Lipídeos , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Gravidez , Resultado da Gravidez , Gravidez em Diabéticas/metabolismo , Ratos , SementesRESUMO
Fornece dados sobre o potencial embriofeto-tóxico do alfa-terpineno no rato. O alfa-terpinemo dissolvido em óleo de milho, foi administrado por entubaçäo gástrica a ratas wistar do dia 6 ao dia 15 de gravidez. As ratas foram pesadas diariamente. No dia 21 de gestaçäo as fêmeas foram anestesiadas com éter etílico, sacrificadas por decapitaçäo e submetidas à cesariana. O n§ de sítios de implantaçäo, de fetos vivos e mortos, de reabsorçoes e de corpos lúteos gravídicos foi registrado. Todos os fetos foram pesados, examinados para malformaçoes visíveis externamente, numerados com caneta especial e fixados em soluçäo de formol a 5 por cento. Um terço dos fetos de cada ninhada, excolhidos ao acaso, foram avaliados quanto a ocorrência de anomalias viscerais por meio de uma técnica de microdissecçäo. O fígado, baço, rins, coraçäo, pulmoes e o timo dos fetos microdissecados também foram pesados. Os fetos retantes foram examinados para detecçäo de malformaçoes de esqueleto, após diafanizaçäo com hidróxido de potássio e coloraçäo com Alizarina Red S. A reduçäo de ganho de peso entre os dias 6 e 11 de gravidez, assim como durante toda a gestaçäo descontado o peso do útero gravídico, indicaram que as duas maiores doses testadas (125 e 250 mg de alfa-terpinemo/Kg peso corporal foram tóxicas para a mäe. A dose mais alta de alfa-terpinemo (250 mg/Kg de peso corporal po) reduziu a razäo entre o n§ de ratas grávidas e o n§ de ratas cruzadas. Uma frequência aumentada de sinais de retardo do crescimento fetal e uma maior incidência de malformaçoes esqueléticas de menor gravidade, foram encontradas em doses superiores a 30 mg de alfa-terpinemo/Kg de peso corporal po. A partir dos dados obtidos neste estudo experimental, o nível máximo de doses em que näo se observam efeitos adversos (NOAEL) para embriofeto-toxic pode ser fixado de 30 mg de alfa-terpinemo/Kg de peso corporal po. Embora näo haja dados disponíveis sobre a exposiçäo humana ao alfa-terpinemo é razoável admitir que níveis de dose comparáveis a este NOAEL obtidos experimentalmente säo improváveis de serem atingidos quando o homem é exposto a óleos essenciais contendo o alfa-terpinemo empregados como aditivos aromatizantes em alimentos ou através do uso de remédios da medicina popular.