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1.
J Chem Ecol ; 45(7): 638-648, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31227972

RESUMO

Although the production of phytohormones has been commonly associated with production of plant defence and stress-related traits, few studies have simultaneously investigated this phenomenon across several plant species that grow along large-scale ecological gradients. To address these knowledge gaps, we performed a common garden experiment with six Cardamine species, which collectively encompass an elevational gradient of 2000 m. We quantified constitutive and Pieris brassicae caterpillars-induced phytohormones and chemical defences in leaves. We found a correlated expression of phytohormone production and the subsequent induction of chemical defences, and this correlated expression reduced herbivore performance. Furthermore, we found that abiotic conditions associated with the optimal elevation range of each species influenced the production of phytohormones and chemical defences, as well as plant growth and productivity. In particular, we found that plant species adapted to milder abiotic conditions at low elevations grew faster, were more productive and produced greater levels of chemical defences. In contrast, plant species adapted to harsher abiotic conditions at high elevations tended to produce greater levels of defence-related oxylipins. Overall, these findings highlight the importance of disentangling the role of phytohormones in mediating plant adaptations to shifting biotic and abiotic conditions.


Assuntos
Cardamine/química , Glucosinolatos/química , Himenópteros/fisiologia , Reguladores de Crescimento de Planta/química , Animais , Cardamine/metabolismo , Cromatografia Líquida de Alta Pressão , Glucosinolatos/farmacologia , Herbivoria , Interações Hospedeiro-Parasita/efeitos dos fármacos , Himenópteros/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/fisiologia , Reguladores de Crescimento de Planta/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Espectrometria de Massas em Tandem
2.
Molecules ; 24(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126050

RESUMO

The present study was conducted to assess the chemical composition of Yellow Maca (Lepidium meyenii) and its biological activity on stallions following oral administration of hypocotyl powder. Maca was subjected to methanolic extraction and the chemical analysis was carried out by LC-MS-QTOF (liquid chromatography-mass spectrometry). Our results showed that Maca contains some effective antioxidants, a high percentage of glucosinolates, and other important components with a high antioxidant capacity. To evaluate the plant biological activity in stallions fed with Maca powder for 60 days, the redox status and some reproductive parameters were investigated. Blood and semen samples were collected at 0, 30, 60, and 90 days from the beginning of this study. Blood samples showed a decrease of the reactive oxygen metabolites, evaluated by d-ROMs test, and an increase of the antioxidant barrier in terms of biological antioxidant potential (BAP test), powerful oxidant capacity (OXY-Adsorbent test), and thiols evaluation (-SHp test). Furthermore, semen samples showed a positive trend during Maca administration in the following parameters: ejaculate volumes and sperm concentrations, total and progressive motility, and acrosome integrity.


Assuntos
Antioxidantes/administração & dosagem , Lepidium/química , Compostos Fitoquímicos/administração & dosagem , Sêmen/fisiologia , Administração Oral , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Glucosinolatos/administração & dosagem , Glucosinolatos/química , Glucosinolatos/farmacologia , Cavalos , Hipocótilo/química , Masculino , Oxirredução/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Pós/administração & dosagem , Espécies Reativas de Oxigênio/sangue , Sêmen/efeitos dos fármacos , Motilidade Espermática/efeitos dos fármacos
3.
Molecules ; 24(4)2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30791395

RESUMO

Bunias erucago belongs to the Brassicaceae family, which represents a forgotten crop of the Euro-Mediterranean area. The aim of the present study was to determine the glucosinolate profile in different plant parts and biological properties (antioxidant, anticholinesterase, and cytotoxic activities) of the isolates containing glucosinolate breakdown products. The chemical profiles were determined by using HPLC-PDA-MS/MS of desulfoglucosinolates and GC-MS of glucosinolate degradation products. The analysis of B. erucago showed the presence of seven glucosinolates: gluconapin (1), glucoraphasatin (2), glucoraphenin (3), glucoerucin (4), glucoraphanin (5), glucotropaeolin (6), and glucosinalbin (7). The total glucosinolate content ranged from 7.0 to 14.6 µmol/g of dry weight, with the major glucosinolate glucosinalbin in all parts. The antioxidant activity of all volatile isolates was not notable. At a tested concentration of 227 µg/mL, flower hydro-distillate (FH) showed good AChE inhibition, i.e., 40.9%, while root hydro-distillate (RH) had good activity against BChE, i.e., 54.3%. FH showed the best activity against both tested human bladder cancer cell lines, i.e., against T24 after 72 h, which have IC50 of 16.0 µg/mL, and against TCCSUP after 48 h with IC50 of 7.8 µg/mL, and can be considered as highly active. On the other hand, RH showed weak activity against tested cancer cells.


Assuntos
Brassicaceae/química , Glucosinolatos/química , Glucosinolatos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem , Compostos Orgânicos Voláteis/química
4.
Nutrients ; 11(2)2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30791362

RESUMO

Edible sprouts with germinating seeds of a few days of age are naturally rich in nutrients and other bioactive compounds. Among them, the cruciferous (Brassicaceae) sprouts stand out due to their high contents of glucosinolates (GLSs) and phenolic compounds. In order to obtain sprouts enriched in these phytochemicals, elicitation is being increasing used as a sustainable practice. Besides, the evidence regarding the bioavailability and the biological activity of these compounds after their dietary intake has also attracted growing interest in recent years, supporting the intake of the natural food instead of enriched ingredients or extracts. Also, there is a growing interest regarding their uses, consumption, and applications for health and wellbeing, in different industrial sectors. In this context, the present review aims to compile and update the available knowledge on the fundamental aspects of production, enrichment in composition, and the benefits upon consumption of diverse edible cruciferous sprouts, which are sources of phenolic compounds and glucosinolates, as well as the evidence on their biological actions in diverse pathophysiological situations and the molecular pathways involved.


Assuntos
Brassica/química , Dieta , Germinação , Glucosinolatos/farmacologia , Fenóis/farmacologia , Brotos de Planta/química , Sementes/química , Brassica/crescimento & desenvolvimento , Humanos , Extratos Vegetais/farmacologia , Brotos de Planta/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento
5.
J Anim Physiol Anim Nutr (Berl) ; 103(3): 822-835, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30734371

RESUMO

The nutritional quality of rapeseed press cakes (RPCs) in piglet feed is closely linked to its digestibility and the content of glucosinolates. This study investigates the significance of intact glucosinolate (glc) levels and degree of glc transformations on piglets performance. Four different RPCs were made from a low glc (11 µmol/g seed DM) containing B. napus L. seed variety Lioness (RPC-LW, RPC-LXW, RPC-LC, RPC-LCD). RPC made from the variety Excalibur containing the upper level of glc (24 µmol/g seed DM) of double rapeseed and produced at higher and prolonged temperature (RPC-UXW) served as negative control, while soya bean protein concentrate served as positive control. Piglets (8 kg) were fed ad libitum diets balanced for RPC protein content, with RPC inclusion of 84-98 g/kg (day 0-14) and 151-178 g/kg (day 15-50). Glc transformation was reduced from 42% to 24% (7.3-4.2 µmol/g RPC) when the temperature input was lowered in the warm pressing of oil, while the glc loss was less pronounced (17%) when cold pressing was applied. The following feed pelleting process further reduced Glc concentration from 11% to 40% in warm-pressed RPCs and 54 to 85% in cold-pressed RPCs. The RPC products replaced soya bean protein without any negative effects on performance, except for piglets served cold-pressed RPC, which had a reduction in average daily weight gain (ADG) (5%-7%, p < 0.05, Day 15-50). RPC in the feed led to increased liver weight in all piglets (p = 0.026). This may point at long-term effects from feeding with RPC. Intestinal absorption of intact glcs was proven by their detection in urine. In conclusion, warm-pressed RPC can be used as feed for piglet, while the presence of active myrosinase may have a negative effect on performance and cakes should either be included in lower amounts than used in the present study (18%) or include myrosinase inactivation before use.


Assuntos
Ração Animal/análise , Brassica rapa/química , Dieta/veterinária , Glucosinolatos/farmacologia , Suínos/crescimento & desenvolvimento , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal/efeitos dos fármacos , Proteínas na Dieta/química , Proteínas na Dieta/metabolismo , Glucosinolatos/administração & dosagem , Glucosinolatos/química , Glucosinolatos/metabolismo , Rim/anatomia & histologia , Rim/efeitos dos fármacos , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Masculino , Nitrogênio/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Ratos , Glândula Tireoide/anatomia & histologia , Glândula Tireoide/efeitos dos fármacos
6.
Nature ; 566(7743): 249-253, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30700914

RESUMO

Environmental genotoxic factors pose a challenge to the genomic integrity of epithelial cells at barrier surfaces that separate host organisms from the environment. They can induce mutations that, if they occur in epithelial stem cells, contribute to malignant transformation and cancer development1-3. Genome integrity in epithelial stem cells is maintained by an evolutionarily conserved cellular response pathway, the DNA damage response (DDR). The DDR culminates in either transient cell-cycle arrest and DNA repair or elimination of damaged cells by apoptosis4,5. Here we show that the cytokine interleukin-22 (IL-22), produced by group 3 innate lymphoid cells (ILC3) and γδ T cells, is an important regulator of the DDR machinery in intestinal epithelial stem cells. Using a new mouse model that enables sporadic inactivation of the IL-22 receptor in colon epithelial stem cells, we demonstrate that IL-22 is required for effective initiation of the DDR following DNA damage. Stem cells deprived of IL-22 signals and exposed to carcinogens escaped DDR-controlled apoptosis, contained more mutations and were more likely to give rise to colon cancer. We identified metabolites of glucosinolates, a group of phytochemicals contained in cruciferous vegetables, to be a widespread source of genotoxic stress in intestinal epithelial cells. These metabolites are ligands of the aryl hydrocarbon receptor (AhR)6, and AhR-mediated signalling in ILC3 and γδ T cells controlled their production of IL-22. Mice fed with diets depleted of glucosinolates produced only very low levels of IL-22 and, consequently, the DDR in epithelial cells of mice on a glucosinolate-free diet was impaired. This work identifies a homeostatic network protecting stem cells against challenge to their genome integrity by AhR-mediated 'sensing' of genotoxic compounds from the diet. AhR signalling, in turn, ensures on-demand production of IL-22 by innate lymphocytes directly regulating components of the DDR in epithelial stem cells.


Assuntos
Transformação Celular Neoplásica/efeitos dos fármacos , Colo/citologia , Interleucinas/farmacologia , Mutagênicos/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Animais , Apoptose/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Neoplasias do Colo/genética , Neoplasias do Colo/prevenção & controle , Dano ao DNA , Dieta/efeitos adversos , Glucosinolatos/administração & dosagem , Glucosinolatos/farmacologia , Imunidade Inata , Interleucinas/biossíntese , Mucosa Intestinal/citologia , Ligantes , Camundongos , Mutagênicos/administração & dosagem , Mutação/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Interleucina/metabolismo , Células-Tronco/citologia , Linfócitos T/metabolismo
7.
J Food Sci ; 84(1): 19-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30561035

RESUMO

Despite the advancement of medical science, diseases are part-and-parcel of human life. Plants have provided humans with medicines since time immemorial, and are still one of the primary sources for drug discovery. Brassica rapa L., commonly known as turnip, is one of the world's oldest cultivated vegetables. Besides being an important vegetable and source of oil, turnip is also used as a traditional medicine for the treatment of headaches, chest complaints, rheumatisms, oedemas, gonorrhoea, syphilis, and rabies. Glucosinolates and isothiocyanates (mainly 2-phenylethyl, 4-pentenyl, and 3-butenyl derivatives) are the main constituents of turnip with diverse bioactivities, especially for the protective effect against cancers. Besides, flavonoids, phenolics, indoles and volatiles are also concomitant in this plant. Pharmacological investigation on turnip revealed the antitumor, antihypertensive, antidiabetic, antioxidant, antiinflammatory, hepatoprotective, and nephroprotective effects. The anticancer property was found to be the most promising biological activity of turnip with 2-phenylethyl isothiocyanate, phenylpropionitrile, brassicaphenanthrene A, 6-paradol, and trans-6-shogaol as the major active constituents. Flavonoids and phenolics with high free radical scavenging activity should be corresponding to the antioxidant effects. Arvelexin, an indole derivative in turnip, was reported with various effects involving antiinflamatory, antihypertensive and hypolipidemic potency. In spite of many studies concerning either the chemical constituents or the biological activities of turnip, only a few cases disclosed the active ingredients responsible for diverse bioactivities. This review summarizes the research progress on the chemistry and health-benefits of turnip over the past 20 years to provide a reference for the further investigation.


Assuntos
Brassica rapa/química , Compostos Fitoquímicos/farmacologia , Analgésicos/farmacologia , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Fármacos Antiobesidade/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Flavonoides/análise , Flavonoides/farmacologia , Glucosinolatos/análise , Glucosinolatos/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Isotiocianatos/análise , Isotiocianatos/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Compostos Fitoquímicos/análise , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/farmacologia
8.
Phytother Res ; 32(11): 2226-2234, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30069944

RESUMO

The beneficial effects of isothiocyanate-based compounds, as well as their safety, have been shown in neuropathological disorders, such as neuropathic pain. Aim of the present work was to study the efficacy of the glucosinolate glucoraphanin (GRA) and the derived isothiocyanate sulforaphane (SFN), secondary metabolites occurring exclusively in Brassicales, on chemotherapy-induced neuropathic pain. Mice were repeatedly treated with oxaliplatin (2.4 mg kg-1 ip) for 14 days to induce neuropathic pain. GRA and SFN effects were evaluated after a single administration on Day 15 or after a daily repeated oral and subcutaneous treatment starting from the first day of oxaliplatin injection until the 14th day. Single subcutaneous and oral administrations of GRA (4.43-119.79 µmol kg-1 ) or SFN (1.33-13.31 µmol kg-1 ) reduced neuropathic pain in a dose-dependent manner. The repeated administration of GRA and SFN (respectively 13.31 and 4.43 µmol kg-1 ) prevented the chemotherapy-induced neuropathy. The co-administration of GRA and SFN in mixture with the H2 S binding molecule, haemoglobin, abolished their pain-relieving effect, which was also reverted by pretreating the animals with the selective blocker of Kv7 potassium channels, XE991. GRA and SFN reduce neuropathic pain by releasing H2 S and modulating Kv7 channels and show a protective effect on the chemotherapy-induced neuropathy.


Assuntos
Glucosinolatos/farmacologia , Sulfeto de Hidrogênio/metabolismo , Imidoésteres/farmacologia , Isotiocianatos/farmacologia , Canal de Potássio KCNQ1/antagonistas & inibidores , Neuralgia/tratamento farmacológico , Compostos Organoplatínicos/efeitos adversos , Animais , Antineoplásicos/efeitos adversos , Masculino , Camundongos , Neuralgia/induzido quimicamente , Oxaliplatina
9.
Ecotoxicol Environ Saf ; 162: 454-463, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30015192

RESUMO

Plant-derived substances, because of high biological activity, arouse interest of many scientists. Thus, plant extracts and pure substances are intensively studied on various insects as potential insecticides. In such studies, D. melanogaster is one of the most important model organisms. In our studies, we analysed the contents of two plant extracts and tested the activity of their main components against fruit flies and compared observed effects to effects caused by crude extracts. Then, we assessed the development of the next, unexposed generation. The chemical analysis of extracts revealed the presence of numerous glycoalkaloids and glucosinolates in Solanum nigrum and Armoracia rusticana extracts. These extracts, as well as their main components, revealed lethal and sublethal effects, such as the altered developmental time of various life stages and malformations of imagoes. Interestingly, the results for the extracts and pure main compounds often varied. Some of the results were also observed in the unexposed generation. These results confirm that the tested plants produce a range of substances with potential insecticidal effects. The different effects of extracts and pure main components suggest the presence of minor compounds, which should be tested as insecticides.


Assuntos
Armoracia/química , Drosophila melanogaster/efeitos dos fármacos , Inseticidas/farmacologia , Estágios do Ciclo de Vida/efeitos dos fármacos , Extratos Vegetais/farmacologia , Solanum nigrum/química , Alcaloides/análise , Alcaloides/farmacologia , Animais , Drosophila melanogaster/fisiologia , Glucosinolatos/análise , Glucosinolatos/farmacologia , Insetos/efeitos dos fármacos , Reprodução
10.
Nutrients ; 10(6)2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866995

RESUMO

Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G0/G1 phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Isotiocianatos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Relação Dose-Resposta a Droga , Glucosinolatos/farmacologia , Células HT29 , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Células MCF-7 , Fatores de Tempo
11.
Nutrients ; 10(5)2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29738500

RESUMO

Crucifer vegetables, Brassicaceae and other species of the order Brassicales, e.g., Moringaceae that are commonly consumed as spice and food, have been reported to have potential benefits for the treatment and prevention of several health disorders. Though epidemiologically inconclusive, investigations have shown that consumption of those vegetables may result in reducing and preventing the risks associated with neurodegenerative disease development and may also exert other biological protections in humans. The neuroprotective effects of these vegetables have been ascribed to their secondary metabolites, glucosinolates (GLs), and their related hydrolytic products, isothiocyanates (ITCs) that are largely investigated for their various medicinal effects. Extensive pre-clinical studies have revealed more than a few molecular mechanisms of action elucidating multiple biological effects of GLs hydrolytic products. This review summarizes the most significant and up-to-date in vitro and in vivo neuroprotective actions of sulforaphane (SFN), moringin (MG), phenethyl isothiocyanate (PEITC), 6-(methylsulfinyl) hexyl isothiocyanate (6-MSITC) and erucin (ER) in neurodegenerative diseases.


Assuntos
Glucosinolatos/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Brassica/química , Humanos , Isotiocianatos/farmacologia , Sulfetos/farmacologia , Tiocianatos/farmacologia , Verduras/química
12.
Biomed Pharmacother ; 102: 670-680, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29604586

RESUMO

Adipocyte differentiation is a critical adaptive response to nutritional overload and affects the metabolic outcome of obesity. Sinigrin (2-propenyl glucosinolate) is a glucosinolate belong to the glucoside contained in broccoli, brussels sprouts, and black mustard seeds. We investigated the effects of sinigrin on adipogenesis in 3T3-L1 preadipocytes and its underlying mechanisms. Sinigrin remarkably inhibited the accumulation of lipid droplets and adipogenesis by downregulating the expression of CCAAT-enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), leptin and aP2. Sinigrin arrested cells in the G0/G1 phase of the cell cycle and increased the expression of p21 and p27. CDK2 expression was suppressed by sinigirn in MDI-induced adipocytes. Sinigrin increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and acetyl-CoA carboxylase (ACC) in the early stage of adipocyte differentiation, suggesting that sinigrin has anti-adipogenic effects through AMPK, MAPK and ACC activation. Sinigrin also inhibited the production of pro-inflammatory cytokines including tumor necrosis factor -alpha (TNF-α) and interleukin (IL)-6, IL-1ß and IL-18. Taken together, these data suggest that sinigrin inhibits early-stage adipogenesis of 3T3-L1 adipocytes through the AMPK and MAPK signaling pathways.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/citologia , Adipócitos/enzimologia , Diferenciação Celular/efeitos dos fármacos , Glucosinolatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Animais , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Clonais , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Mitose/efeitos dos fármacos , PPAR gama/metabolismo
13.
Phytochemistry ; 145: 121-127, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29126020

RESUMO

The adverse effect of glucosinolates on diverse phytophagous insects is well documented, but its impact on insect physiology has remained enigmatic. Here we report insights into detrimental effects of plant glucosinolate molecule, sinigrin, on Helicoverpa armigera growth and development. In-silico screening of multiple glucosinolates predicted sinigrin as one of the potential inhibitor of H. armigera cathepsin B and L. Insects fed on sinigrin containing diet showed significantly reduced growth (20-30%), delayed pupation (10-15%), decreased fecundity (50-80%) and developmental abnormalities. Further, sinigrin showed 50-60% inhibition of ex-vivo cathepsin like activity which might be a reason for growth and development related abnormalities. In-vitro and mass spectrometry studies highlighted the cytotoxicity caused due to the hydrolysis of sinigrin, into toxic isothiocyanates, in presence of H. armigera whole body extract. In conclusion, insect cathepsin inhibition and isothiocyanate mediated cytotoxicity lead to the dual adverse effect of sinigrin on H. armigera.


Assuntos
Glucosinolatos/farmacologia , Mariposas/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glucosinolatos/química , Glucosinolatos/isolamento & purificação , Conformação Molecular , Mariposas/crescimento & desenvolvimento , Células Sf9 , Spodoptera/citologia , Relação Estrutura-Atividade
14.
J Agric Food Chem ; 65(33): 7186-7191, 2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28805380

RESUMO

Ongoing consumer concerns over using synthetic additives in foods has strongly influenced efforts worldwide to source suitable natural alternatives. In this study, the antibacterial efficacy of polyacetylene and glucosinolate compounds was evaluated against both Gram positive and Gram negative bacterial strains. Falcarinol [minimum inhibitory concentration (MIC) = 18.8-37.6 µg/mL] demonstrated the best overall antibacterial activity, while sinigrin (MIC = 46.9-62.5 µg/mL) was the most active glucosinolate compound. High-performance liquid chromatography with a diode array detector analysis showed falcarinol [85.13-244.85 µg/g of dry weight (DW)] to be the most abundant polyacetylene within six of the eight carrot (Daucus carota) cultivars investigated. Meanwhile, sinigrin (100.2-244.3 µg/g of DW) was the most abundant glucosinolate present within the majority of broccoli (Brassica oleracea) cultivars investigated using ultra performance liquid chromatography-tandem mass spectrometry analysis. The high abundance of both falcarinol and sinigrin within these respective species suggests that they could serve as potential sources of natural antibacterial agents for use as such in food products.


Assuntos
Antibacterianos/farmacologia , Brassica/química , Daucus carota/química , Glucosinolatos/farmacologia , Extratos Vegetais/farmacologia , Poli-Inos/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Aditivos Alimentares/química , Aditivos Alimentares/farmacologia , Glucosinolatos/química , Extratos Vegetais/química , Poli-Inos/química , Espectrometria de Massas em Tandem
15.
World J Gastroenterol ; 23(23): 4146-4157, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28694655

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols (i.e., resveratrol, quercetin, coumestrol, anthocyanins, epigallocatechin gallate and curcumin), carotenoids (i.e., lycopene, astaxanthin and fucoxanthin) and glucosinolates (i.e., glucoraphanin, sulforaphane, sinigrin and allyl-isothiocyanate), on the reversion of fatty liver. Although the mechanism of action is not yet fully elucidated, in some cases an indirect interaction with mitochondrial metabolism is expected. We believe that such knowledge will eventually translate into the development of novel therapeutic approaches for fatty liver.


Assuntos
Antioxidantes/farmacologia , Fígado Gorduroso/dietoterapia , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Animais , Antocianinas/farmacologia , Carotenoides/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Cumestrol/farmacologia , Curcumina/farmacologia , Metabolismo Energético , Fígado Gorduroso/metabolismo , Glucosinolatos/farmacologia , Humanos , Imidoésteres/farmacologia , Isotiocianatos/farmacologia , Lipogênese , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ciências da Nutrição , Estresse Oxidativo , Polifenóis/farmacologia , Quercetina/farmacologia , Resveratrol , Estilbenos/farmacologia , Xantofilas/farmacologia
16.
Plant Signal Behav ; 12(6): e1334749, 2017 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-28594299

RESUMO

Members of the nitrate transporter 1/peptide transporter family (NPF) are multifunctional transporters of various compounds including plant hormones and play important roles in plant growth and responses to environmental stress. Recently, we found that Arabidopsis GTR1 (also known as NPF2.10) takes up gibberellic acid and jasmonoyl-L-isoleucine in addition to glucosinolates. For normal plant growth, GTR1 is regulated at the gene expression level; however, it is unclear whether post-translational regulation also occurs. Here, we found that dimerization of GTR1, possibly induced by dephosphorylation of the Thr residue located between the possible transmembrane regions, regulates its plasma membrane localization, leading to transport of glucosinolates and gibberellic acid in Xenopus oocytes. These findings suggest that dimerization of multifunctional transporters contributes to their activities at the plasma membrane.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Membrana Celular/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Multimerização Proteica , Animais , Membrana Celular/efeitos dos fármacos , Giberelinas/metabolismo , Glucosinolatos/farmacologia , Proteínas Mutantes/metabolismo , Oócitos/metabolismo , Transporte Proteico/efeitos dos fármacos , Xenopus
17.
Chem Biol Interact ; 272: 28-36, 2017 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-28483571

RESUMO

Atherosclerosis is a complex inflammatory disease associated with elevated levels of atherogenic molecules for leukocyte recruitment. Sinigrin (2-propenylglucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health promotion. In this study, we examined the effect of sinigrin on development of atherosclerosis in ApoE-/- mice and the expression of adhesion molecules in vascular smooth muscle cells (VSMCs). The serum concentrations of lactate dehydrogenase (LDH), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), calcium (Ca2+), and pro-inflammatory cytokines were reduced by sinigrin treatment in ApoE-/- mice. In addition, oral administration of sinigrin attenuated the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), C-C motif chemokine ligand 2 (CCL2), and CCL5 on aorta tissues and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), liver X receptor (LXR), sterol regulatory element-binding protein-2 (SREBP-2), and low density lipoprotein receptor (LDLR) on liver tissues in ApoE-/- mice. To provide a potential mechanism underlying the action of sinigrin, we evaluated the in vitro effect of sinigrin on the expression of the VCAM-1 in TNF-α-induced VSMCs. The increased expression of VCAM-1 by TNF-α stimulation was significantly suppressed by the treatment of sinigrin (1-100 µg/ml) and sinigrin inhibited the nuclear translocation of NF-κB and the phosphorylation of p38 MAPK and JNK pathways, suggesting that sinigrin decreases the TNF-α-stimulated VCAM-1 expression through the suppression of NF-κB and MAP kinases signaling pathways. Overall, sinigrin has the potential to be used in reducing the risks of atherosclerosis.


Assuntos
Aterosclerose/prevenção & controle , Dieta Hiperlipídica , Expressão Gênica/efeitos dos fármacos , Glucosinolatos/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Aorta/diagnóstico por imagem , Aorta/metabolismo , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/patologia , Quimiocina CCL2/metabolismo , Quimiocina CCL5/metabolismo , Progressão da Doença , Glucosinolatos/uso terapêutico , Molécula 1 de Adesão Intercelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipoproteínas LDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Molécula 1 de Adesão de Célula Vascular/análise , Molécula 1 de Adesão de Célula Vascular/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Insect Biochem Mol Biol ; 85: 21-31, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28455184

RESUMO

Phytophagous insects have to deal with toxic defense compounds from their host plants. Although it is known that insects have evolved genes and mechanisms to detoxify plant allochemicals, how specialist and generalist precisely respond to specific secondary metabolites at the molecular level is less understood. Here we studied the larval performance and transcriptome of the generalist moth Heliothis virescens and the specialist butterfly Pieris brassicae feeding on Arabidopsis thaliana genotypes with different glucosinolate (GS) levels. H. virescens larvae gained significantly more weight on the GS-deficient mutant quadGS compared to wild-type (Col-0) plants. On the contrary, P. brassicae was unaffected by the presence of GS and performed equally well on both genotypes. Strikingly, there was a considerable differential gene expression in H. virescens larvae feeding on Col-0 compared to quadGS. In contrast, compared to H. virescens, P. brassicae displayed a much-reduced transcriptional activation when fed on both plant genotypes. Transcripts coding for putative detoxification enzymes were significantly upregulated in H. virescens, along with digestive enzymes and transposable elements. These data provide an unprecedented view on transcriptional changes that are specifically activated by GS and illustrate differential molecular responses that are linked to adaptation to diet in lepidopteran herbivores.


Assuntos
Borboletas/efeitos dos fármacos , Glucosinolatos/farmacologia , Herbivoria , Mariposas/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Arabidopsis , Borboletas/genética , Borboletas/metabolismo , Regulação para Baixo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Inativação Metabólica/genética , Proteínas de Insetos/metabolismo , Larva/efeitos dos fármacos , Mariposas/genética , Mariposas/metabolismo , Análise de Sequência de RNA
19.
Diabetes ; 66(5): 1222-1236, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28209760

RESUMO

Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) alleviates obesity and insulin resistance in mice; however, Nrf2 inducers are not clinically available owing to safety concerns. Thus, we examined whether dietary glucoraphanin, a stable precursor of the Nrf2 inducer sulforaphane, ameliorates systemic energy balance, chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)-fed mice. Glucoraphanin supplementation attenuated weight gain, decreased hepatic steatosis, and improved glucose tolerance and insulin sensitivity in HFD-fed wild-type mice but not in HFD-fed Nrf2 knockout mice. Compared with vehicle-treated controls, glucoraphanin-treated HFD-fed mice had lower plasma lipopolysaccharide levels and decreased relative abundance of the gram-negative bacteria family Desulfovibrionaceae in their gut microbiomes. In HFD-fed mice, glucoraphanin increased energy expenditure and the protein expression of uncoupling protein 1 (Ucp1) in inguinal and epididymal adipose depots. Additionally, in this group, glucoraphanin attenuated hepatic lipogenic gene expression, lipid peroxidation, classically activated M1-like macrophage accumulation, and inflammatory signaling pathways. By promoting fat browning, limiting metabolic endotoxemia-related chronic inflammation, and modulating redox stress, glucoraphanin may mitigate obesity, insulin resistance, and NAFLD.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Endotoxemia , Glucosinolatos/farmacologia , Imidoésteres/farmacologia , Resistência à Insulina , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Desulfovibrio , Dieta Hiperlipídica , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação , Peroxidação de Lipídeos/efeitos dos fármacos , Lipopolissacarídeos/sangue , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Proteína Desacopladora 1/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo
20.
Int Immunopharmacol ; 45: 163-173, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28219839

RESUMO

Sinigrin (2-propenyl glucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health. This study investigated the effect of sinigrin on macrophage function, including the activity of Nod-like receptor protein 3 (NLRP3) inflammasome. In a concentration-dependent manner, sinigrin inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production and the expression of COX-2 and prostaglandin E2 (PGE2) in RAW 264.7 cells. In addition, sinigrin significantly suppressed the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 via suppression of MAPK phosphorylation and nuclear factor-kappa B (NF-κB) activity. Treatment with sinigrin decreased IL-1ß and IL-18 production and concurrently suppressed NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 expression in LPS/ATP-stimulated cells, suggesting that the blocking of NLRP3 inflammasome activation prevented the production of both cytokines. Collectively, these results suggest that sinigrin has immunomodulatory effects by suppressing the production of inflammatory mediators, possibly by inhibiting the NF-κB/MAPK pathways or NLRP3 inflammasome activation. Our findings also provide evidence that the pharmacological modulation of sinigrin could have an anti-inflammatory effect.


Assuntos
Anti-Inflamatórios/farmacologia , Glucosinolatos/farmacologia , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
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