RESUMO
In the present study we evaluate the effect of superparamagnetic iron oxide nanoparticles (SPIONs) carrying usnic acid (UA) as chemical cargo on the soil microbial community in a dystrophic red latosol (oxysol). Herein, 500 ppm UA or SPIONs-framework carrying UA were diluted in sterile ultrapure deionized water and applied by hand sprayer on the top of the soil. The experiment was conducted in a growth chamber at 25 °C, with a relative humidity of 80% and a 16 h/8 h light-dark cycle (600 lx light intensity) for 30 days. Sterile ultrapure deionized water was used as the negative control; uncapped and oleic acid (OA) capped SPIONs were also tested to assess their potential effects. Magnetic nanostructures were synthesized by a coprecipitation method and characterized by scanning and transmission electron microscopy (SEM and TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), zeta potential, hydrodynamic diameter, magnetic measurements, and release kinetics of chemical cargo. Uncapped and OA-capped SPIONs did not significantly affect soil microbial community. Our results showed an impairment in the soil microbial community exposed to free UA, leading to a general decrease in negative effects on soil-based parameters when bioactive was loaded into the nanoscale magnetic carrier. Besides, compared to control, the free UA caused a significant decrease in microbial biomass C (39%), on the activity of acid protease (59%), and acid phosphatase (23%) enzymes, respectively. Free UA also reduced eukaryotic 18S rRNA gene abundance, suggesting a major impact on fungi. Our findings indicate that SPIONs as bioherbicide nanocarriers can reduce the negative impacts on soil. Therefore, nanoenabled biocides may improve agricultural productivity, which is important for food security due to the need of increasing food production.
Assuntos
Nanopartículas de Magnetita , Nanopartículas de Magnetita/química , Solo , Nanopartículas Magnéticas de Óxido de Ferro , ÁguaRESUMO
Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.
Assuntos
Benzofuranos/química , Benzofuranos/farmacologia , Potássio/química , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Benzofuranos/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Líquens/metabolismoRESUMO
Ischemia-reperfusion (I/R) injury causes oxidative stress, leading to severe cardiac dysfunction. Thus, biologically active compounds with antioxidant properties may be viewed as a promising therapeutic strategy against oxidative-related cardiac disorders. Usnic acid (UA), a natural antioxidant, was complexed with ß-cyclodextrin (ßCD) to improve its bioavailability. Wistar male rats were orally treated with the free form of UA (50 mg/kg) or the inclusion complex UA/ßCD (50 mg/kg) for seven consecutive days. Afterward, hearts were subjected to I/R injury, and the cardiac contractility, rhythmicity, infarct size, and antioxidant enzyme activities were evaluated. Here, we show that neither UA nor UA/ßCD treatments developed signs of toxicity. After I/R injury, animals treated with UA/ßCD showed improved post-ischemic cardiac functional recovery while the release of cell injury biomarkers decreased. Following reduced cardiac damage, a lower incidence of ventricular arrhythmias and smaller myocardial infarct size were associated with reduced lipid peroxidation, along with preserved activity of antioxidant enzymes compared to untreated rats. Surprisingly, uncomplexed UA did not protect hearts against IR injury. Altogether, our results indicate that the inclusion complex UA/ßCD is a critical determining factor responsible for the cardioprotection action of UA, suggesting the involvement of an antioxidant-dependent mechanisms. Moreover, our findings support that UA/ßCD is a structurally engineered compound with active cardioprotective properties.
Assuntos
Benzofuranos/farmacologia , Cardiotônicos/farmacologia , beta-Ciclodextrinas/química , Animais , Benzofuranos/química , Benzofuranos/uso terapêutico , Cardiotônicos/química , Cardiotônicos/uso terapêutico , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , TermogravimetriaRESUMO
PURPOSE: To evaluate the safety and potential healing efficacy of the topical ocular administration of a gelatin membrane containing usnic acid/liposomes (UALs) for corneal cicatrization. UALs have shown healing activity in animal models of dermal burn lesions. We evaluated the safety of topical ocular administration of UAL and its potential healing efficacy as an ophthalmic treatment on chemical lesions in rabbit eyes. METHOD: The Draize test was used to check for ocular toxicity and the score was zero at each observation, indicating the ocular safety of a gelatin membrane containing usnic acid/liposome. Its potential healing efficacy as an ophthalmic treatment on chemical lesions in rabbit eyes was also assessed. RESULTS: After epithelial removal and treatment with UAL, there was a 49.4 % reduction in injury under in vivo conditions compared with a 36.6 % reduction in the control, a gelatin membrane containing liposome without usnic acid. Histological analysis of ocular surface chemical injury-tissue sections after treatment with UAL supported these observations. The corneal expression of VEGF and TGF-ß1increased by 70 % and 50 % respectively following treatment with UAL gelatin membrane. CONCLUSION: These results indicate the potential therapeutic application of UAL gelatin membranes as an ophthalmic treatment that may be used for corneal cicatrization.
Assuntos
Benzofuranos/administração & dosagem , Cicatriz/tratamento farmacológico , Córnea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Cicatrização/efeitos dos fármacos , Administração Oftálmica , Animais , Benzofuranos/química , Galinhas , Córnea/irrigação sanguínea , Feminino , Gelatina/administração & dosagem , Gelatina/química , Lipossomos/administração & dosagem , Lipossomos/química , Neovascularização Fisiológica/efeitos dos fármacos , Soluções Oftálmicas/químicaRESUMO
BACKGROUND: Breast cancer is the most common cancer types among women. Recent researches have focused on determining the efficiency of alternative molecules and miRNAs in breast cancer treatment. The aim of this study was to determine the effect of usnic acid response-miR-185-5p on proliferation in the breast cancer cell and to determine its relationship with apoptosis pathway. METHODS: The cell proliferation and cell apoptosis rate were significantly increased following the ectopic expression of miR-185-5p in BT-474 cells. Furthermore, the results of cell cycle assay performed by flow cytometry revealed that the transfection with miR-185-5p induced G1/S phase arrest. The apoptosis-related genes expression analysis was performed by qRT-PCR and the direct target of miR-185-5p in BT-474 cells was identified by western blot and luciferase reporter assay. RESULTS: Our data showed that miR-185-5p can cause significant changes in apoptosis-related genes expression levels, suggesting that cell proliferation was suppressed by miR-185-5p via inducing apoptosis in breast cancer cells. According to western blot results, miR-185-5p lead to decrease BCL2 protein level in BT-474 cells and direct target of miR-185-5p was identified as BCL by luciferase reporter assay. CONCLUSION: This study revealed that miR-185-5p may be an effective agent in the treatment of breast cancer.
Assuntos
Benzofuranos/metabolismo , Neoplasias da Mama/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Apoptose , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , TransfecçãoRESUMO
Currently, the control of schistosomiasis is based on a single drug, praziquantel, which is effective against all species of Schistosoma but only in the adult stage, presenting a schistosomicidal deficit at the other developmental stages of the parasites. Recently our research group has demonstrated that the potassium salt of usnic acid (PS-UA) presented schistosomicidal property against couples of adult worms of S. mansoni. Thus, the present study seeks to report for the first time the in vitro activity of PS-UA against different developmental stages of S. mansoni (schistosomules and young worms). As schistosomicide parameters, we evaluated motility, mortality, cell viability of the worms and tegument changes by scanning electron microscopy (SEM). After 3 h exposure, PS-UA was lethal to schistosomules at concentrations of 100 and 50 µM, whereas for concentrations 25 and 12.5 µM, 38 and 18% of mortality and 62 and 24% changes in motility, respectively, were reached. Yet for schistosomules, concentration of 25 µM caused 90 and 100% of death after 6 and 12 h, respectively. In the concentration of 12.5 µM at intervals of 12 and 24 h mortality was 68 and 100%, respectively. For young worms, after 3 h of exposure at concentrations of 200 and 100 µM caused 57 and 27% mortality, respectively. After 12 and 24 h, these concentrations caused mortality of 90 and 100% and 47 and 60% respectively. After 24 h, concentrations of 50 and 25 µM caused 80 and 30% change in motility, respectively. However, at the 12.5 µM concentration no change was observed. In addition, PS-UA reduced the cellular viability of young worms by 50.98% and 85.87% at concentrations of 100 and 200 µM, respectively. In both stages of worms and at different exposure intervals, PS-UA caused alterations such as: dorsoventral contraction, peeling, swelling, blisters, erosion, exposure of subtegumental tissue and disintegration of tegument. According to the results, changes in motility and mortality caused by PS-UA against schistosomules and young worms were concentration and time-dependents, also PS-UA even at low concentration, was able to cause profound ultrastructural changes in the integument of the worms. PS-UA is a promising candidate as prophylactic agent in the control of schistosomiasis mansoni.
Assuntos
Benzofuranos/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Schistosoma mansoni/crescimento & desenvolvimento , Schistosoma mansoni/ultraestruturaRESUMO
Here, we report enhanced the in vitro effect of potassium usnate on coupled adult Schistosoma mansoni worms at different time intervals and concentrations. The evaluated schistosomicidal parameters were the following: motility, mortality, fecundity and integumentary changes, as viewed in photomicrographs. Potassium usnate was able to cause 100 and 50% mortality at 100 and 50⯵M concentrations, respectively, after 24â¯h of exposure, while 25 and 12.5⯵M concentrations caused changes in motility at 48 and 72â¯h, and lethality at 96 and 120â¯h respectively. Eggs were not detected at any of the concentrations analyzed. Photomicrographs revealed morphological tegument alterations within all periods of observation, such as swelling, blisters, dorsoventral contraction, short and curved worms. In conclusion, our results indicate that potassium usnate represents a possible candidate for a new drug in the control of schistosomiasis.
Assuntos
Anti-Helmínticos/farmacologia , Benzofuranos/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/prevenção & controle , Análise de Variância , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/química , Benzofuranos/administração & dosagem , Benzofuranos/química , Relação Dose-Resposta a Droga , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Camundongos , Movimento/efeitos dos fármacos , Fotomicrografia , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/tratamento farmacológico , Fatores de TempoRESUMO
BACKGROUND: Breast cancer is the most common cancer types among women. Recent researches have focused on determining the efficiency of alternative molecules and miRNAs in breast cancer treatment. The AIMof this study was to determine the effect of usnic acid response-miR-185-5p on proliferation in the breast cancer cell and to determine its relationship with apoptosis pathway. METHODS: The cell proliferation and cell apoptosis rate were significantly increased following the ectopic expression of miR-185-5p in BT-474 cells. Furthermore, the results of cell cycle assay performed by flow cytometry revealed that the transfection with miR-185-5p induced G1/S phase arrest. The apoptosis-related genes expression analysis was performed by qRT-PCR and the direct target of miR-185-5p in BT-474 cells was identified by western blot and luciferase reporter assay. RESULTS: Our data showed that miR-185-5p can cause significant changes in apoptosis-related genes expression levels, suggesting that cell proliferation was suppressed by miR-185-5p via inducing apoptosis in breast cancer cells. According to western blot results, miR-185-5p lead to decrease BCL2 protein level in BT-474 cells and direct target of miR-185-5p was identified as BCL by luciferase reporter assay. CONCLUSION: This study revealed that miR-185-5p may be an effective agent in the treatment of breast cancer.
Assuntos
Humanos , Feminino , Benzofuranos/metabolismo , Neoplasias da Mama/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , MicroRNAs/genética , Neoplasias da Mama/metabolismo , Transfecção , Transdução de Sinais , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
To obtain usnic acid potassium salt (PS-UA), the usnic acid (UA) was extracted and purified from the lichen Cladonia substellata, and modified to produce PS-UA. The structure was determined by 1H-NMR, IR and elemental analysis, ratified through computational models, as well as identification the site of K+ insertion in the molecule. Antinociceptive activity was detected through contortions in mice induced by acetic acid and formalin (phases I and II) after treatments with 10 and 20 mg/kg of PS-UA, indicating interference in both non-inflammatory and inflammatory pain. After oral administration at doses of 500, 1000 and 2000 mg/kg, no deaths of mice with treatments below 2000 mg/kg were observed. Except for body weight gain, food and water consumption decreased with treatments of 1000 and 2000 mg/kg, and the number of segmented leukocytes was higher for both treatments. Regarding serum levels, cholesterol and triglycerides decreased, however, there was an increase in hepatic transaminases with both treatments. Liver and kidney histological changes were detected in treatments of 2000 mg/kg, while the spleen was preserved. The PS-UA demonstrated antinociceptive activity while the acute toxicity at the concentration of 2000 mg/kg was the only dose that presented morphological changes in the liver and kidney.
Assuntos
Analgésicos/farmacologia , Benzofuranos/farmacologia , Benzofuranos/toxicidade , Testes de Toxicidade Aguda , Animais , Comportamento Animal/efeitos dos fármacos , Benzofuranos/química , Modelos Animais de Doenças , Comportamento de Ingestão de Líquido , Comportamento Alimentar , Feminino , Camundongos , Conformação Molecular , Especificidade de Órgãos/efeitos dos fármacosRESUMO
Usnic acid (UA) is one of the pharmacologically most important compounds produced by several lichen species. To better understand the mechanism of action (MOA) of this important substance, this study examined the genotoxicity attributed to UA and its influence on mutagens with varying MOA using the micronucleus (MN) test in Chinese hamster ovary cells (CHO). Additional experiments were conducted to investigate the effect of UA on colon carcinogenesis in Wistar rats employing the aberrant crypt focus (ACF) assay. In vitro studies showed a significant increase in the frequency of MN in cultures treated with the highest UA concentration tested (87.13 µM). In contrast, UA concentrations of 10.89, 21.78, or 43.56 µM produced an approximate 60% reduction in chromosomal damage induced by doxorubicin, hydrogen peroxide, and etoposide, indicating an antigenotoxic effect. In the ACF assay, male Wistar rats treated with different UA doses (3.125, 12.5, or 50 mg/kg b.w.) and with the carcinogen 1,2-dimethylhydrazine exhibited a significantly lower incidence of neoplastic lesions in the colon than animals treated only with the carcinogen. Data suggest that the MOA responsible for the chemopreventive effect of UA may be related to interaction with DNA topoisomerase II and/or the antioxidant potential of the compound.