RESUMO
This study investigates the chemical composition of the essential oil obtained from the leaves of Bocageopsis multiflora (Mart.) R.E.Fr (Annonaceae), examining its effectiveness in combating both the larvae and adult forms of Aedes aegypti mosquitoes. Additionally, for a deeper understanding of the insecticidal activity, toxicity properties and molecular docking calculations were conducted using the main compounds of this essential oil. GC/MS analysis revealed the presence of 26 constituents, representing 95.2% of the essential oil, with the major components identified as the sesquiterpenes α-selinene, ß-selinene, and ß-elemene. Larvicidal assays demonstrated potent activity of this essential oil with significant LC50 values of 40.8 and 39.4 µg/mL at 24 and 48 h, respectively. Adulticidal assessments highlighted strong efficacy with LC50 of 12.5 µg/mL. Molecular docking analysis identified optimal interaction activities of α-selinene and ß-selinene with key Aedes proteins. The in silico studies comparing synthetic insecticides with the major sesquiterpenes of the essential oil revealed that ß-selinene exhibited a significantly higher binding affinity compared to the other two sesquiterpenes. Also, ADMET studies of the three main sesquiterpenes indicated acceptable drug-like properties. In these findings, safety evaluations showed low toxicity and skin sensitization for the main sesquiterpenes, contrasting with commercial synthetic insecticides. Therefore, in silico analyses suggest promising interactions with Aedes proteins, indicating its potential as an effective alternative to conventional insecticides These results show the larvicidal and adulticidal potential of the essential oil from Bocageopsis multiflora against Aedes aegypti, supported by its predominant constituents, α-selinene, ß-selinene and ß-elemene.
Assuntos
Aedes , Inseticidas , Larva , Simulação de Acoplamento Molecular , Óleos Voláteis , Animais , Aedes/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Inseticidas/química , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Folhas de Planta/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Cromatografia Gasosa-Espectrometria de MassasRESUMO
Leishmania amazonensis is the etiological agent of tegumentary leishmaniasis, a disease characterized by the emergence of cutaneous and mucocutaneous ulcerated lesions that can evolve into severe destruction of skin tissue. Treatment of the disease is often accompanied by high toxicity and variable efficacy. Essential oils stand out for having diverse pharmacological properties. Here, we screened a panel of fourteen essential oils for their anti-L.â amazonensis activity, cytotoxicity, and chemical profile. Lippia sidoides (LSEO) and Piper callosum (PCEO) oils displayed the best anti-promastigote and anti-amastigote activities with IC50 of 31 and 21â µg/ml, respectively. PCEO was the safest oil with a desirable selectivity index >10. In addition, PCEO showed no cytotoxicity against the VERO line and erythrocytes. PCEO-treated amastigotes displayed mitochondrial membrane depolarization and high levels of intracellular ROS. Safrole (54.72 %) was the main component of PCEO. The results described here highlight the use of essential oils to combat tegumentary leishmaniasis.
Assuntos
Antiprotozoários , Leishmania , Leishmaniose , Óleos Voláteis , Piper , Humanos , Animais , Camundongos , Óleos Voláteis/química , Piper/química , Antiprotozoários/química , Leishmaniose/tratamento farmacológico , Camundongos Endogâmicos BALB CRESUMO
Staphylococci are one of the most common causes of biofilm-related infections. Such infections are hard to treat with conventional antimicrobials, which often lead to bacterial resistance, thus being associated with higher mortality rates while imposing a heavy economic burden on the healthcare system. Investigating antibiofilm strategies is an area of interest in the fight against biofilm-associated infections. Previously, a cell-free supernatant from marine-sponge-associated Enterobacter sp. inhibited staphylococcal biofilm formation and dissociated the mature biofilm. This study aimed to identify the chemical components responsible for the antibiofilm activity of Enterobacter sp. Scanning electron microscopy confirmed that the aqueous extract at the concentration of 32 µg/mL could dissociate the mature biofilm. Liquid chromatography coupled with high-resolution mass spectrometry revealed seven potential compounds in the aqueous extract, including alkaloids, macrolides, steroids, and triterpenes. This study also suggests a possible mode of action on staphylococcal biofilms and supports the potential of sponge-derived Enterobacter as a source of antibiofilm compounds.
Assuntos
Anti-Infecciosos , Infecções Estafilocócicas , Humanos , Staphylococcus , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes , Infecções Estafilocócicas/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Black fungi of the Herpotrichiellaceae family are agents of chromoblastomycosis and phaeohyphomycosis. There are few therapeutic options for these infections and it is common to associate antifungal drugs in their treatment. OBJECTIVES: To investigate the Medicines for Malaria Venture (MMV) Pathogen Box® for possible compounds presenting synergism with antifungal drugs used to treat black fungal infections. METHODS: An initial screening of the Pathogen Box® compounds was performed in combination with itraconazole or terbinafine at sub-inhibitory concentrations against Fonsecaea pedrosoi. Hits were further tested against eight Herpotrichiellaceae using the checkerboard method. FINDINGS: No synergism was observed with terbinafine. MMV687273 (SQ109) and MMV688415 showed synergism with itraconazole against F. pedrosoi. Synergism of these compounds was confirmed with some black fungi by the checkerboard method. SQ109 and itraconazole presented synergism for Exophiala dermatitidis, F. pedrosoi, F. monophora and F. nubica, with fungicidal activity for F. pedrosoi and F. monophora. MMV688415 presented synergism with itraconazole only for F. pedrosoi, with fungicidal activity. The synergic compounds had high selectivity index values when combined with itraconazole. MAIN CONCLUSIONS: These compounds in combination, particularly SQ109, are promising candidates to treat Fonsecaea spp. and E. dermatitidis infections, which account for most cases of chromoblastomycosis and phaeohyphomycosis.
Assuntos
Ascomicetos , Cromoblastomicose , Malária , Feoifomicose , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Cromoblastomicose/diagnóstico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/microbiologia , Itraconazol/farmacologia , Malária/tratamento farmacológico , Testes de Sensibilidade Microbiana , Feoifomicose/tratamento farmacológico , Terbinafina/uso terapêuticoRESUMO
Fusarium incarnatum-equiseti species complex (FIESC) is considered as one of the richest insecticolous species. Fusarium species synthesize toxic secondary metabolites that are not fully understood. Mycotoxin production and pathogenicity on germinating seeds, seedlings, and leaves must be carefully studied for the use of Fusarium species in the biological control of insect pests. In this study, we evaluated the mycotoxin production and phytopathogenic potential of entomopathogenic strains of Fusarium sulawesiensis (1), F. pernambucanum (3), and F. caatingaense (23). The phytopathogenicity tests of F. caatingaense (URM 6776, URM 6777, URM 6778, URM 6779, and URM 6782) were performed during the development of bean (Phaseolus vulgaris, Vigna unguiculata, and Phaseolus lunatus), and corn (Zea mays) seedlings, using four treatments (soil infestation with the inoculum, spraying on leaves, root dip, and negative control). The mycotoxins, monoacetyl-deoxynivalenols (AcDON), deoxynivalenol (DON), beauvericin (BEA), fusarenone-X (FUS), T-2 toxin (T2), diacetoxyscirpenol (DAS), and zearalenone (ZEA), were detected in the study; BEA (detected in 25 strains) and FUS (detected in 21 strains) were found to be predominant. None of the strains showed any ability to cause disease or virulence in beans and corn. The FIESC strains showed a highly variable production of mycotoxins without the potential to be used as phytopathogenic agents for the cultures tested.
Assuntos
Fusarium , Micotoxinas , Brasil , Fungos , Zea maysRESUMO
OBJECTIVE: The present report describes the enzymatic acylation of umbelliferone with different vinyl esters as acyl donors biocatalyzed by the commercial lipase Novozym® 435, and the investigation for their antibacterial activity against ATCC and clinical strains isolated from hospital infection sites. RESULTS: The umbelliferone esters (1-5) were synthesized through the acylation reaction of 7-hydroxy-2H-chromen-2-one with different long chain vinyl esters catalyzed by the lipase Novozym 435. The reaction conditions were: 10% Novozym 435; tetrahydrofuran:acetone (3:1) for the reactions with acetate, propionate and butyrate vinyl esters 50-90% conversion, and (9:1) for decanoate and laurate vinyl esters 10-15% conversion; acyl donor/umbelliferone molar ratio of 10:1 and 60 °C. All the umbelliferone esters were characterized NMR and (HRMS). The antibacterial activity of the products were tested using the broth microdilution method in order to determine the minimum inhibitory concentration (MIC). The results displayed by 7-laurate and 7-decanoate-umbelliferone esters showed the highest antibacterial potential, with 1 mM inhibitory activity for ATCC 33591, a methicillin and oxacillin resistant Staphylococcus aureus strain. They were also able to inhibit gram-negative bacterial strains, such as Pseudomonas aeruginosa (MIC 0.5 mM) and Klebsiella pneumoniae (MIC 1 mM). In addition, 7-laurate- and 7-decanoate-umbelliferone esters were able to inhibit all clinical strains (MIC 1 mM; except 7-laurate-umbelliferone in which MIC 0.5 mM against 55a). CONCLUSIONS: This is the first study performing the biocatalysis of umbelliferone followed by the purification of the products and the antibacterial evaluation.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Ésteres/farmacologia , Lipase/química , Umbeliferonas/farmacologia , Antibacterianos/síntese química , Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Biocatálise , Enzimas Imobilizadas/química , Enzimas Imobilizadas/genética , Ésteres/síntese química , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Lipase/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Transdução de Sinais/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Umbeliferonas/síntese químicaRESUMO
Herbal medicines containing Passiflora species have been widely used to treat anxiety since ancient times. The species Passiflora incarnata L. is included in many Pharmacopoeias, and it is the most used species in food, cosmetic, and pharmaceutical industries. However, there are around 600 species of the genus Passiflora and probably other species that can be used safely. Thus, this article was based on a search into the uses of the main species of the genus Passiflora with anxiolytic activity and its main secondary metabolites and some pharmacological studies, patents, and registered products containing Passiflora. Furthermore, the Brazilian Regulatory Health Agency Datavisa, Medicines and Healthcare Products Regulatory Agency of the United Kingdom, and the European Medicines Agency websites were consulted. The results showed that Passiflora species have health benefits but clinical trials are still scarce. The complexity of Passiflora extracts creates challenges for the development of herbal medicines. P. incarnata is the most studied species of the genus and the most used in natural anxiolytic herbal medicine formulations. However, there are hundreds of Passiflora species potentially useful for medicinal and nutraceutical purposes that are still little explored.
Assuntos
Ansiolíticos/farmacologia , Passiflora/química , Extratos Vegetais/farmacologia , Plantas Medicinais , Ansiolíticos/uso terapêutico , Brasil , Humanos , Patentes como Assunto , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Plantas Medicinais/químicaRESUMO
The difficulties encountered and the numerous side effects present in the treatment of cutaneous leishmaniasis have encouraged the research for new compounds that can complement or replace existing treatment. The growing scientific interest in the study of plants, which are already used in folk remedies, has led our group to test Endlicheria bracteolata essential oil against Leishmania amazonensis. Several species of the Lauraceae family, or their compounds, have relevant antiprotozoal activities Therefore, the biological potential on L. amazonensis forms from the essential oil of Endlicheria bracteolata leaves was verified for the first time in that work. The antileishmanial activity was evaluated against promastigotes and intracellular amastigotes, and cytotoxicity were performed with J774.G8, which were incubated with different concentrations of E. bracteolata essential oil. Transmission electron microscopy and flow cytometry were performed with E. bracteolata essential oil IC50. Promastigote forms showed E. bracteolata essential oil IC50 of 7.945 ± 1.285 µg/mL (24 h) and 6.186 ± 1.226 µg/mL (48 h), while for intracellular amastigote forms it was 3.546 ± 1.184 µg/mL (24 h). The CC50 was 15.14 ± 0.090 µg/mL showing that E. bracteolata essential oil is less toxic to macrophages than to parasites. Transmission electron microscopy showed that E. bracteolata essential oil treatment is capable of inducing mitochondrial damage to promastigote and intracellular amastigote forms, while flow cytometry showed ΔÑ°m disruption in treated parasites. These results could bring about new possibilities to develop products based on E. bracteolata essential oil to treat cutaneous leishmaniasis, especially for people who cannot receive the conventional therapy.
Assuntos
Antiprotozoários/farmacologia , Leishmania mexicana/química , Leishmania/efeitos dos fármacos , Óleos Voláteis/farmacologia , Animais , Antiprotozoários/química , Cromatografia Gasosa-Espectrometria de Massas , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Macrófagos/patologia , Macrófagos/ultraestrutura , Camundongos , Óleos Voláteis/química , Testes de Sensibilidade ParasitáriaRESUMO
NEW FINDINGS: What is the central question of this study? Early-life adversity is associated with increased risk for obesity and metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination of both. What is the main finding and its importance? Early-life adversity increases vulnerability to later-life obesity and metabolic dysfunction, indicating that genetics and adult lifestyle are not the only determinants of obesity and related metabolic dysfunction. Moreover, consumption of cafeteria diet exacerbated metabolic dysfunction associated with early-life adversity, suggesting that poor dietary choices might have a bigger impact in the context of early-life adversity. ABSTRACT: Early-life adversity has become recognized as an important factor contributing to adult obesity and associated metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction associated with early-life adversity result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination. Interestingly, both early-life adversity and later-life dietary choices affect immune function, favouring pro-inflammatory mechanisms that are associated with obesity-related metabolic dysfunction. To investigate the unique and/or interactive effects of early-life adversity and later-life dietary choices for increased vulnerability to obesity and metabolic dysfunction, and specifically the role of the immune system in this vulnerability, we combined a naturalistic rat model of early-life scarcity-adversity with a rat model of obesity, the cafeteria diet. Our results indicate that early-life adversity alone induces insulin resistance, reduces pancreatic insulin secretion, plasma concentrations of triglycerides and cholesterol, and increases fasting glucose and tumour necrosis factor-α plasma concentrations. Importantly, animals exposed to adverse rearing were more vulnerable to metabolic dysregulation associated with the cafeteria diet, given that they consumed more energy, showed more severe hepatic steatosis and increased concentrations of the pro-inflammatory cytokine interleukin-1ß than normally reared animals fed the cafeteria diet. Together, our results suggest that early-life adversity negatively programmes physiological systems that regulate metabolic function and increases vulnerability to obesity and metabolic dysfunction in adulthood. These results highlight the intrinsic relationship between the quality of the early postnatal environment and later-life dietary choices on adult health outcomes.
Assuntos
Resistência à Insulina/fisiologia , Obesidade/metabolismo , Triglicerídeos/sangue , Animais , Dieta , Modelos Animais de Doenças , Feminino , Insulina/sangue , Interleucina-1beta/sangue , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangueRESUMO
Species of the genus Alpinia are widely used by the population and have many described biological activities, including activity against insects. In this paper, we describe the bioactivity of the essential oil of two species of Alpinia genus, A. zerumbet and A. vittata, against Rhodnius nasutus, a vector of Chagas disease. The essential oils of these two species were obtained by hydrodistillation and analyzed by GC-MS. The main constituent of A. zerumbet essential oil (OLALPZER) was terpinen-4-ol, which represented 19.7% of the total components identified. In the essential oil of A. vittata (OLALPVIT) the monoterpene ß-pinene (35.3%) was the main constituent. The essential oils and their main constituents were topically applied on R. nasutus fifth-instar nymphs. In the first 10 min of application, OLALPVIT and OLALPZER at 125 µg/mL provoked 73.3% and 83.3% of mortality, respectively. Terpinen-4-ol at 25 µg/mL and ß-pinene at 44 µg/mL provoked 100% of mortality. The monitoring of resistant insects showed that both essential oils exhibited antifeedant activity. These results suggest the potential use of A. zerumbet and A. vittata essential oils and their major constituents to control R. nasutus population.
Assuntos
Alpinia/química , Insetos Vetores/efeitos dos fármacos , Inseticidas/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Rhodnius/efeitos dos fármacos , Animais , Doença de Chagas/parasitologia , Doença de Chagas/transmissão , Vetores de Doenças , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Insetos Vetores/parasitologia , Inseticidas/química , Óleos Voláteis/química , Testes de Sensibilidade Parasitária , Rhodnius/parasitologiaRESUMO
BACKGROUND: Borojoa sorbilis (Ducke) is an Amazonian species with edible fruits that are widely consumed by the local population, but little studied and not yet economically explored. Thus the aim of this study was to describe the chemical composition, volatile compounds, nutritional aspects and antioxidant activity of the fruit pulp and peel of B. sorbilis. RESULTS: Headspace solid-phase microextraction, using polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber, resulted in the identification of 59 substances in the pulp and peel of B. sorbilis fruits after analysis of the chromatograms obtained by gas chromatography-mass spectrometry using polar and nonpolar columns. Esters were the most abundant. Moisture, lipids, protein, dietary fiber, ash, carbohydrate, total energy value, titratable acid, soluble solids and pH were measured. Protein amount, fat content and antioxidant activity were low in both pulp and peel. Carbohydrate content was 179.2 and 134.9 g kg-1 in pulp and peel, respectively. CONCLUSION: This is the first report on the chemical characteristics, flavor and nutritional aspects of B. sorbilis fruit, which is essential to its economic exploitation. The high energy value associated with the carbohydrate content, plus the low fat content, contribute to a possible use of B. sorbilis fruits as a food supplement. © 2018 Society of Chemical Industry.
Assuntos
Frutas/química , Extratos Vegetais/química , Rubiaceae/química , Compostos Orgânicos Voláteis/química , Brasil , Fibras na Dieta/análise , Cromatografia Gasosa-Espectrometria de Massas , Valor NutritivoRESUMO
CONTEXT: Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease characterized by lesional polymorphism and the commitment of skin surface. Previous reports demonstrated that the Citrus genus possess antimicrobial activity. OBJECTIVE: This study evaluated the anti-L. amazonensis activity of Citrus sinensis (L.) Osbeck (Rutaceae) extracts. MATERIALS AND METHODS: Citrus sinensis dried leaves were subjected to maceration with hexane (CH), ethyl acetate (CEA), dichloromethane/ethanol (CD/Et - 1:1) or ethanol/water (CEt/W - 7:3). Leishmania amazonensis promastigotes were treated with C. sinensis extracts (1-525 µg/mL) for 120 h at 27 °C. Ultrastructure alterations of treated parasites were evaluated by transmission electron microscopy. Cytotoxicity of the extracts was assessed on RAW 264.7 and J774.G8 macrophages after 48-h treatment at 37 °C using the tetrazolium assay. In addition, Leishmania-infected macrophages were treated with CH and CD/Et (10-80 µg/mL). RESULTS: CH, CD/Et and CEA displayed antileishmanial activity with 50% inhibitory activity (IC50) of 25.91 ± 4.87, 54.23 ± 3.78 and 62.74 ± 5.04 µg/mL, respectively. Parasites treated with CD/Et (131.2 µg/mL) presented severe alterations including mitochondrial swelling, lipid body formation and intense cytoplasmic vacuolization. CH and CD/Et demonstrated cytotoxic effects similar to that of amphotericin B in the anti-amastigote assays (SI of 2.16, 1.98 and 1.35, respectively). Triterpene amyrins were the main substances in CH and CD/Et extracts. In addition, 80 µg/mL of CD/Et reduced the number of intracellular amastigotes and the percentage of infected macrophages in 63% and 36%, respectively. CONCLUSION: The results presented here highlight C. sinensis as a promising source of antileishmanial agents.
Assuntos
Antiprotozoários/farmacologia , Citrus sinensis/química , Leishmania/efeitos dos fármacos , Macrófagos/parasitologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antiprotozoários/isolamento & purificação , Antiprotozoários/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Citrus sinensis/toxicidade , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Leishmania/crescimento & desenvolvimento , Leishmania/ultraestrutura , Camundongos , Testes de Sensibilidade Parasitária , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta/toxicidade , Plantas Medicinais , Células RAW 264.7 , Solventes/químicaRESUMO
Current treatments for leishmaniasis present some difficulties due to their toxicity, the use of the intravenous route for administration and therapy duration, which may lead to treatment discontinuation. The aim of this study is to investigate new treatment alternatives to improve patients well being. Therefore, we evaluated the inhibitory effect of (-)α-bisabolol, a sesquiterpene alcohol found in various essential oils of different plant species, against the promastigotes and intracellular amastigotes forms of Leishmania amazonensis, as well as the cytotoxic, morphological and ultrastructural alterations of treated cells. Promastigotes forms of L. amazonensis were incubated with (-)α-bisabolol to determine the antileishmanial activity of this compound. The cytotoxicity effect was evaluated by testing against J774.G8 cells. After these tests, the infected and uninfected cells with L. amazonensis were used to determine if the (-)α-bisabolol was able to kill intracellular parasites and to cause some morphological changes in the cells. The (-)α-bisabolol compound showed significant antileishmanial activity against promastigotes with a 50% effective concentration of 8.07 µg/ml (24 h) and 4.26 µg/ml (48 h). Against intracellular amastigotes the IC50 (inhibitory concentration) of (-)α-bisabolol (24 h) was 4.15 µg/ml. The (-)α-bisabolol also showed a cytotoxic effect against the macrophage strain J774.G8. The value of 50% cytotoxic concentration was 14.82 µg/ml showing that (-)α-bisabolol is less toxic to macrophages than to the parasite. Ultrastructural studies of treated promastigotes and amastigotes showed several alterations, such as loss of cytoplasmic organelles, including the nucleus, and the presence of lipid inclusions. This study showed that (-)α-bisabolol has promising antileishmanial properties, as it can act against the promastigote forms and is able to penetrate the cell, and is also active against the amastigote forms. About 69% of the promastigotes forms suffered mitochondrial membrane damage after treatment with IC50 of (-)α-bisabolol, suggesting inhibition of the metabolic activity of parasites. These results open new prospects for research that can contribute to the development of products based on essential oils or isolated compounds from plants for the treatment of cutaneous leishmaniasis.
Assuntos
Antiprotozoários/farmacologia , Leishmania mexicana/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Antiprotozoários/toxicidade , Linhagem Celular , Citometria de Fluxo , Humanos , Concentração Inibidora 50 , Leishmania mexicana/crescimento & desenvolvimento , Leishmania mexicana/ultraestrutura , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Sesquiterpenos Monocíclicos , Sesquiterpenos/toxicidadeRESUMO
Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease.
Assuntos
Produtos Biológicos/química , Leishmaniose/imunologia , Animais , Anti-Inflamatórios/química , Antineoplásicos/química , Comunicação Celular , Citocinas/metabolismo , Desenho de Fármacos , Humanos , Inflamação , Leishmania , Leucotrieno B4/química , Extratos Vegetais/químicaRESUMO
Low-protein diet is the recommended nutritional intervention for nondialysis chronic kidney disease (CKD) patients because excess protein intake can damage kidney function and produce uremic toxins. Some of these toxins are generated from amino acids breakdown by gut microbiota as p-cresyl sulfate and indoxyl sulfate that have been clearly associated with cardiovascular mortality in CKD patients. Another uremic toxin, trimethylamine N-oxide (TMAO), a degradation product of choline and L-carnitine (which come mainly from animal protein such as red meat and eggs) is now considered as a proatherogenic metabolite. In the present review, we will highlight the relationship between TMAO, diet and cardiovascular aspects, and the potential concerns about TMAO in nondialysis CKD patients.
Assuntos
Dieta com Restrição de Proteínas , Microbioma Gastrointestinal , Metilaminas/sangue , Insuficiência Renal Crônica/sangue , Animais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/microbiologia , Carnitina/sangue , Colina/sangue , Modelos Animais de Doenças , Ovos , Humanos , Metilaminas/química , Ensaios Clínicos Controlados Aleatórios como Assunto , Carne Vermelha , Insuficiência Renal Crônica/dietoterapia , Insuficiência Renal Crônica/microbiologiaRESUMO
Human tegumentary leishmaniasis (HTL) is a serious tropical disease caused by Leishmania amazonensis. Developing new leishmanicidal agents can help overcome current treatment challenges, such as drug resistance and toxicity. Essential oils are a source of lipophilic substances with diverse therapeutic properties. This study aimed to determine the anti-L. amazonensis activity, cytotoxicity, and chemical profile of Allium sativum essential oil (ASEO). The effect of ASEO on parasite and mammalian cells viability was evaluated using resazurin and MTT assays, respectively. The oil's effect against intracellular amastigotes was also determined. Transmission electron microscopy was used to assess the ultrastructural changes induced by ASEO. In addition, the chemical constituents of ASEO were identified by gas chromatography-mass spectrometry (GC-MS). The cytotoxic potential was evaluated in vitro and in silico. The oil displayed IC50 of 1.76, 3.46, and 3.77 µg/mL against promastigotes, axenic, and intracellular amastigotes, respectively. Photomicrographs of treated parasites showed plasma membrane disruption, increased lipid bodies, and autophagic-like structures. ASEO chemical profiling revealed 1,2,4,6-tetrathiepane (24.84%) and diallyl disulfide (16.75%) as major components. Computational pharmacokinetics and toxicological analysis of ASEO's major components demonstrated good oral bioavailability and better toxicological endpoints than the reference drugs. Altogether, the results suggest that ASEO could be an alternative drug candidate against HTL.
RESUMO
Ambelania duckei Markgr is a species of the Apocynaceae family, native to the Amazon region that is unexplored from a nutritional point of view and studied in relation to its chemical constituents. This work presents an unprecedented study of the proximate composition, lipid profile, a chromatographic analysis, and the antioxidant activity of extracts obtained from the pulp, peel and seeds of the fruit. The results showed that potassium, calcium, and magnesium stood out as the most abundant key minerals in the fruit peel and pulp, with an emphasis on the potassium present in the fruit pulp at 1750.0 mg/100 g. The peel had the highest content of total phenolics (374.86 mg/g), flavonoids (15.54 mg/g), tannins (27.45 mg/g) and O-diphenols (379.36 mg/g; 645.71 mg/g). The antioxidant activity (AA) was highest in the peel compared to the pulp in the DPPH, ABTS, and ORAC tests showing: IC50 of 29.82; 43.67; and 407.13 µg/mL, respectively but a lower activity for the Fe2+ chelator. The analysis of the lipid fractions from the peel, pulp, and seeds of the A. duckei fruit resulted in 14 types of fatty acids. The major fatty acids found in the three parts of the fruit were oleic acid (peel, 22.52 %), palmitic acid (pulp, 17.34 %), and linoleic acid (seeds, 47.99 %). The lipid profile and nutritional aspects had a PUFA/SFA ratio (0.4-1.8) in the different parts of the A. duckei fruit; the atherogenic and thrombogenic indexes were higher in the peel (1.23) and pulp (0.62), respectively. The ratio between the hypocholesterolemic and hypercholesterolemic fatty acids (0.5 - 3.8) calculated for the fruit are within the desirable range for a nutritious food. The chromatographic analysis of the volatile organic compounds (VOCs) from the peel and pulp of the fruit, identified 74 VOCs, of which 60.9 % are related to terpenes, and emit notes such as cucumber, green, fatty, floral, and mint, due to the presence of substances with OAVs > 10, especially α-ionone, 1,8-cineole, 2,4-decadienal, and dodecanal. The analysis of the MS and MS/MS spectra of the chromatograms obtained by LC- QTOF-HRMS led to the identification of 26 compounds in the peel, seeds and pulp of A. duckei, such as fatty acids, phenolic acid, flavonoids, proanthocyanidins, alkaloids, and terpenoids. The results show that the pulp of A. duckei has potential as nourishing food and the nutritional and chemical aspects of the peel can be applied to commercial applications.
Assuntos
Apocynaceae , Frutas , Frutas/química , Antioxidantes/análise , Espectrometria de Massas em Tandem , Flavonoides/análise , Ácidos Graxos/análise , Terpenos/análise , Potássio/análiseRESUMO
Ambelania acida is native to the Amazon region, with few published studies of its fruits. We examined the proximate composition of its fruits, including minerals, fatty acids, volatile organic compounds (VOCs), as well as its antioxidant capacity. The protein contents (2.61%) of the pulp and seeds (13.6%) were higher than observed in other taxa of the family or in other tropical fruits. Peel and pulp showed high contents of potassium, calcium, and magnesium, and the potassium content in the pulp was 1125 mg/100 g. The peel had higher contents of total phenolics, tannins, and ortho-diphenols than the pulp, as well as better antioxidant activity as evidenced by 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and Fe2+ chelating activity assays. GC-MS analyses identified 42 VOCs in the peel and pulp, with more than 90% being classified as terpenes. Eleven types of fatty acids were identified in the lipid fractions of the peel, pulp, and seeds. Linoleic acid, an essential fatty acid for humans, was the principal fatty acid in the edible portion of the fruit, therefore, evidencing its nutritionally significant profile for the fruits when considering the relationship among polyunsaturated, saturated, and monounsaturated fatty acids. The information gathered here indicates that this native fruit is a healthy food source and its cultivation and consumption should be stimulated.
Assuntos
Antioxidantes , Frutas , Humanos , Frutas/química , Antioxidantes/química , Minerais/análise , Potássio , Ácido Linoleico/análiseRESUMO
Alpinia zerumbet, a species of the Zingiberaceae family, is a common plant in tropical and subtropical areas used in traditional medicine to treat various diseases and also included as food in the traditional Okinawan diet (Japan). The leaves and rhizomes of this plant are used as spice and flavoring in foods such as rice, meats, and pasta. Studies of the chemical and nutritional characteristics of fresh leaves and of leaves submitted to thermal treatments such as boiling and steaming are lacking. In the current study, the leaves of A. zerumbet were subjected to boiling or steaming for 10, 20, and 30 min as part of the thermal treatments. The study also provides noteworthy results regarding the proximate composition, physical-chemical data, minerals, phenolic compounds, antioxidant activity, volatile compounds, and LC-MS chromatographic profiles of the extracts produced with fresh leaves and with thermal treatments. The carbohydrate content of A. zerumbet leaves improved during the thermal treatments, showing an increase after steaming (18.86 to 19.79%) and boiling for 30 min (25.85%). After boiling treatment for 20 min, a significant amount of protein was found (6.79%) and all heat treatments resulted in low content of lipid (<1.0%). The boiling treatment for 10 min (BT10) resulted in the highest concentrations of total phenolic components (TPC), 339.5 mg/g, and flavonoids (TF), 54.6 mg/g, among the three thermal treatments (BT10, BT20 and BT30). The results of the steaming treatments (ST 10, 20, and 30 min) differed, with ST20 leading to higher TPC (150.4 mg/g) and TF (65.0 mg/g). The quantity of total phenolics and flavonoids, as well as the antioxidant activity, were significantly affected by the cooking method and the length of time of sample exposure to heat. The samples boiled for 30 and 10 min had higher concentrations of antioxidant activity as measured by the phosphomolybdenum and DPPH methods (151.5 mg/g of extract and 101.5 µg/mL, respectively). Thirty-eight volatile organic compounds (VOCs) were identified by chromatographic analysis of fresh and thermally treated leaves of A. zerumbet. Terpenoids were the predominant class of volatile compounds in the fresh leaves and in all thermal treatments. p-Cymene, 1,8-cineole, 4-terpineol, linalool, α-copaene and ß-bisabolene have the greatest impact on overall aroma perception, with odor activity values (OAV) greater than five. Among the phenolic compounds identified by LC-HRMS in the extracts of fresh and thermally treated leaves were proanthocyanidins, (+) catechin, (-) epicatechin, quercetin-3-O-glucoronide, isorhamnetin-3-O-glucoronide, kaempferol-3-O-rutinoside, pinocembrin, alpinetin, pinostrobin, and other compounds. The present results support the traditional use of this plant as a potential food with properties that certainly contribute to health improvement.
Assuntos
Alpinia , Antioxidantes , Antioxidantes/análise , Alpinia/química , Alimento Funcional/análise , Fenóis/análise , Flavonoides/análiseRESUMO
The essential oils obtained from leaves of Piper duckei and Piper demeraranum by hydrodistillation were analyzed by gas chromatography-mass spectrometry. The main constituents found in P. demeraranum oil were limonene (19.3%) and ß-elemene (33.1%) and in P. duckei oil the major components found were germacrene D (14.7%) and trans-caryophyllene (27.1%). P. demeraranum and P. duckei oils exhibited biological activity, with IC(50) values between 15 to 76 µg mL(-1) against two Leishmania species, P. duckei oil being the most active. The cytotoxicity of the essential oils on mice peritoneal macrophage cells was insignificant, compared with the toxicity of pentamidine. The main mono- and sesquiterpene, limonene (IC(50) = 278 µM) and caryophyllene (IC(50) = 96 µM), were tested against the strains of Leishmania amazonensis, and the IC(50) values of these compounds were lower than those found for the essential oils of the Piper species. The HET-CAM test was used to evaluate the irritation potential of these oils as topical products, showing that these oils can be used as auxiliary medication in cases of cutaneous leishmaniasis, with less side effects and lower costs.