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1.
Cells ; 13(14)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39056770

RESUMO

Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides including octadecaneuropeptide (ODN). We have previously reported that ODN rescues neurons and astrocytes from 6-OHDA-induced oxidative stress and cell death. The purpose of this study was to examine the potential implication of miR-34b, miR-29a, and miR-21 in the protective activity of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Flow cytometry analysis showed that 6-OHDA increased the number of early apoptotic and apoptotic dead cells while treatment with the subnanomolar dose of ODN significantly reduced the number of apoptotic cells induced by 6-OHDA. 6-OHDA-treated astrocytes exhibited the over-expression of miR-21 (+118%) associated with a knockdown of miR-34b (-61%) and miR-29a (-49%). Co-treatment of astrocytes with ODN blocked the 6-OHDA-stimulated production of ROS and NO and stimulation of Bax and caspase-3 gene transcription. Concomitantly, ODN down-regulated the expression of miR-34b and miR-29a and rescued the 6-OHDA-associated reduced expression of miR21, indicating that ODN regulates their expression during cell death. Transfection with miR-21-3p inhibitor prevented the effect of 6-OHDA against cell death. In conclusion, our study indicated that (i) the expression of miRNAs miR-34b, miR-29a, and miR-21 is modified in astrocytes under 6-OHDA injury and (ii) that ODN prevents this deregulation to induce its neuroprotective action. The present study identified miR-21 as an emerging candidate and as a promising pharmacological target that opens new neuroprotective therapeutic strategies in neurodegenerative diseases, especially in Parkinson's disease.


Assuntos
Apoptose , Astrócitos , Sobrevivência Celular , MicroRNAs , Estresse Oxidativo , Oxidopamina , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina/farmacologia , Ratos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Inibidor da Ligação a Diazepam/metabolismo , Inibidor da Ligação a Diazepam/genética , Espécies Reativas de Oxigênio/metabolismo , Neuropeptídeos/metabolismo , Neuropeptídeos/genética , Fragmentos de Peptídeos , Ratos Wistar
2.
PLoS One ; 19(6): e0304021, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38875282

RESUMO

Milk thistle seed oil is still not a well-known edible oil. Silybum marianum (milk thistle), is present in several countries and is the only known representative of the genus Silybum. However, Silybum eburneum, which is an endemic plant in Spain, Kenya, Morocco, Algeria, and Tunisia, is considered a marginalized species. The present work is the first report that gives information on the lipid and phenolic profiles of Tunisian S. eburneum seed oil compared to those of Tunisian S. marianum seed oil. In addition, the antioxidant properties of these oils were determined with DPPH, FRAP, and KRL assays, and their ability to prevent oxidative stress was determined on human monocytic THP-1 cells. These oils are characterized by high amounts of unsaturated fatty acids; linoleic acid and oleic acid are the most abundant. Campesterol, sitosterol, stigmasterol, and ß-amyrin were the major phytosterols identified. α-tocopherol was the predominant tocopherol found. These oils also contain significant amounts of phenolic compounds. The diversity and richness of Silybum marianum and Silybum eburneum seed oils in unsaturated fatty acids, phenolic compounds, and tocopherols are associated with high antioxidant activities revealed by the DPPH, FRAP, and KRL assays. In addition, on THP-1 cells, these oils powerfully reduced the oxidative stress induced by 7-ketocholesterol and 7ß-hydroxycholesterol, two strongly pro-oxidant oxysterols often present at increased levels in patients with age-related diseases. Silybum marianum and Silybum eburneum seed oils are therefore important sources of bioactive molecules with nutritional interest that prevent age-related diseases, the frequency of which is increasing in all countries due to the length of life expectancy.


Assuntos
Antioxidantes , Fitosteróis , Óleos de Plantas , Sementes , Silybum marianum , Silybum marianum/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Óleos de Plantas/análise , Sementes/química , Antioxidantes/análise , Antioxidantes/farmacologia , Antioxidantes/química , Humanos , Fitosteróis/análise , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Estresse Oxidativo/efeitos dos fármacos , Células THP-1
3.
Int J Mol Sci ; 25(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38732259

RESUMO

Neuroinflammation, a hallmark of various central nervous system disorders, is often associated with oxidative stress and neuronal or oligodendrocyte cell death. It is therefore very interesting to target neuroinflammation pharmacologically. One therapeutic option is the use of nutraceuticals, particularly apigenin. Apigenin is present in plants: vegetables (parsley, celery, onions), fruits (oranges), herbs (chamomile, thyme, oregano, basil), and some beverages (tea, beer, and wine). This review explores the potential of apigenin as an anti-inflammatory agent across diverse neurological conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease), cancer, cardiovascular diseases, cognitive and memory disorders, and toxicity related to trace metals and other chemicals. Drawing upon major studies, we summarize apigenin's multifaceted effects and underlying mechanisms in neuroinflammation. Our review underscores apigenin's therapeutic promise and calls for further investigation into its clinical applications.


Assuntos
Anti-Inflamatórios , Apigenina , Doenças Neuroinflamatórias , Apigenina/farmacologia , Apigenina/uso terapêutico , Humanos , Animais , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo
4.
Plants (Basel) ; 13(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611518

RESUMO

Silybum marianum and Silybum eburneum are wild edible Mediterranean plants used in the human diet. This study presents the initial findings on the phytochemical characterization of Tunisian S. marianum and S. eburneum organs. It examined their mineral, sugar, organic acid, polyphenolic, and seed storage protein contents, as well as their antioxidant potential. In S. marianum, stems had high sodium and potassium contents, while the immature and mature seeds were rich in calcium and magnesium. However, S. eburneum had high potassium levels in stems and high sodium and calcium levels in the flowers. S. marianum showed substantial fructose variation among its organs. Conversely, S. eburneum exhibited significant heterogeneity in glucose, sucrose, and maltose levels across its organs, with maltose exclusively detected in the immature seeds. A notable organ-dependent distribution of organic acids was observed among the two species. Higher levels of phenolic contents were detected in both mature and immature seeds in both species compared to the other plant parts. The seeds possessed higher antioxidant activities than other plant organs. In both S. marianum and S. eburneum seeds, albumins and globulins were the predominant protein fractions. This study brings evidence supporting the important potential of Silybum organs as sources of nutrients with antioxidant properties for producing functional food.

5.
Biochimie ; 222: 1-8, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38408719

RESUMO

Rutin, a phenolic compound, exhibits a diverse range of biological properties, including antioxidant, anti-inflammatory, and antimicrobial effects. In this study, we aimed to investigate the potential of rutin, a naturally occurring plant bioactive molecule, to mitigate the neurotoxic effects induced by aluminum chloride (AlCl3). Over a period of 6 weeks, rats were intraperitoneally injected with AlCl3 at a weekly dose of 60 mg/kg, while rutin treatment was administered orally via gavage at a daily dose of 30 mg/kg. AlCl3 exposure resulted in a significant increase lipid peroxidation (LPO) by 316.24%, nitrate levels by 504.14%, and tumor necrosis factor-alpha (TNF-α) levels by 93.82% in brain mitochondria. Additionally, AlCl3 exposure led to a reduction in glutathione levels and the activity of antioxidant enzymes, including superoxide dismutase (SOD) by 19.74%, glutathione peroxidase (GPx) by 44.76%, and catalase by 50.50%. There was also a significant decline in the activity of mitochondrial complex enzymes. In contrast, rutin treatment significantly enhanced the activity of antioxidant enzymes while concurrently reducing lipid peroxidation levels in rats. Specifically, rutin administration exerted a modulatory effect on the inflammatory response triggered by aluminum exposure, effectively suppressing the excessive production of nitrate and TNF-α. These findings highlight the potential of rutin as an effective therapeutic strategy in mitigating and combating neuro-inflammation and oxidative stress associated with aluminum-induced toxicity, thereby effectively restoring mitochondrial function.


Assuntos
Cloreto de Alumínio , Peroxidação de Lipídeos , Mitocôndrias , Rutina , Animais , Rutina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Masculino , Cloreto de Alumínio/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Síndromes Neurotóxicas/prevenção & controle , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ratos Wistar , Alumínio/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Modelos Animais de Doenças , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/prevenção & controle , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico
6.
Curr Res Toxicol ; 6: 100153, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379847

RESUMO

On murine N2a cells, 7-ketocholesterol induced an oxiapotophagic mode of cell death characterized by oxidative stress (reactive oxygen species overproduction on whole cells and at the mitochondrial level; lipid peroxidation), apoptosis induction (caspase-9, -3 and -7 cleavage, PARP degradation) and autophagy (increased ratio LC3-II / LC3-I). Oxidative stress was strongly attenuated by diphenyleneiodonium chloride which inhibits NAD(P)H oxidase. Mitochondrial and peroxisomal morphological and functional changes were also observed. Down regulation of PDK1 / Akt signaling pathways as well as of GSK3 / Mcl-1 and Nrf2 pathways were simultaneously observed in 7-ketocholesterol-induced oxiapoptophagy. These events were prevented by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by LY-294002, a PI3-K inhibitor, demonstrated an essential role of PI3-K in cell rescue. The rupture of oxidative stress in 7-ketocholesterol-induced oxiapoptophagy was also associated with important modifications of glutathione peroxidase, superoxide dismutase and catalase activities as well as of glutathione peroxidase-1, superoxide dismutase-1 and catalase level and expression. These events were also counteracted by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by mercaptosuccinic acid, a glutathione peroxidase inhibitor, showed an essential role of this enzyme in cell rescue. Altogether, our data support that the reactivation of PI3-K and glutathione peroxidase activities by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol are essential to prevent 7KC-induced oxiapoptophagy.

7.
Adv Exp Med Biol ; 1440: 163-191, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38036880

RESUMO

Oxysterols or cholesterol oxidation products are a class of molecules with the sterol moiety, derived from oxidative reaction of cholesterol through enzymatic and non-enzymatic processes. They are widely reported in animal-origin foods and prove significant involvement in the regulation of cholesterol homeostasis, lipid transport, cellular signaling, and other physiological processes. Reports of oxysterol-mediated cytotoxicity are in abundance and thus consequently implicated in several age-related and lifestyle disorders such as cardiovascular diseases, bone disorders, pancreatic disorders, age-related macular degeneration, cataract, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, and some types of cancers. In this chapter, we attempt to review a selection of physiologically relevant oxysterols, with a focus on their formation, properties, and roles in health and disease, while also delving into the potential of natural and synthetic molecules along with bacterial enzymes for mitigating oxysterol-mediated cell damage.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doenças Neurodegenerativas , Oxisteróis , Animais , Colesterol , Oxirredução , Esteróis
8.
Nutrients ; 15(18)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37764861

RESUMO

Thymus atlanticus (Lamiaceae) is a plant endemic to the Mediterranean basin that is found in significant quantities in the arid regions of Morocco. Thymus atlanticus is used in traditional medicine to treat infectious and non-infectious diseases. It is also used for the isolation of essential oils and for the seasoning of many dishes in the Mediterranean diet. The major constituents of Thymus atlanticus are saponins, flavonoids, tannins, alkaloids, various simple and hydroxycinnamic phenolic compounds, and terpene compounds. Several of these compounds act on signaling pathways of oxidative stress, inflammation, and blood sugar, which are parameters often dysregulated during aging. Due to its physiochemical characteristics and biological activities, Thymus atlanticus could be used for the prevention and/or treatment of age-related diseases. These different aspects are treated in the present review, and we focused on phytochemistry and major age-related diseases: dyslipidemia, cardiovascular diseases, and type 2 diabetes.

9.
Discov Med ; 35(177): 590-611, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553312

RESUMO

BACKGROUND: Herbal medicinal products containing Vaccinium myrtillus L. (bilberry) fruits and fruit extracts are widely available in the market. Although bilberry leaves and stems are considered as bio-waste, they contain much higher levels of phenolic compounds than fruits. The study aimed to investigate the antimicrobial and anticancer potential of aerial part extracts from Vaccinium myrtillus L. (V. myrtillus, VM) plants harvested at high altitudes in Armenian landscape and characterize the bioactive phytochemicals. MATERIAL AND METHODS: For evaluation of antioxidant properties, chemical-based tests (total phenolic and flavonoid content, and antiradical activity in 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) tests) and cellular antioxidant activity (CAA) assay were applied. Genotoxicity and anticancer properties of the extract alone and in combination with fluorouracil were explored in human cancer and normal cell lines. Antibacterial properties of V. myrtillus extract alone and in combination with antibiotics, as well as their effect on proton-flux rate through cell membrane were explored on bacterial strains. The characterization of active phytochemicals was done using Liquid Chromatography-Quadrupole-Orbitrap High-Resolution Mass Spectrometry (LC-Q-Orbitrap HRMS). RESULTS: The V. myrtillus aerial part extract demonstrated promising antioxidant properties in all tests. The selective cytotoxic activity was documented against various cancer cell lines (human colon adenocarcinoma (HT29), human breast cancer (MCF-7) and human cervical carcinoma (HeLa)), while it did not inhibit the growth of tested human normal primary renal mixed epithelial cells (HREC) even at 10-fold higher concentrations. The extract did not have genotoxic properties in comet assay making it a potential source for the development of anticancer preparations. The investigated extract did not directly inhibit the growth of Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium) strains at up to 1 mg/mL concentration. However, V. myrtillus extract enhanced the kanamycin intake and increased its efficiency against E. coli strain. The phytochemical characterization of the extract showed the presence of different groups of phenolics. CONCLUSIONS: Based on obtained data, we suggest the aerial parts of the V. myrtillus plant as an alternative source of bioactive natural products for food supplements, nutraceuticals, functional foods and medicine.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Vaccinium myrtillus , Humanos , Vaccinium myrtillus/química , Vaccinium myrtillus/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Antibacterianos/farmacologia , Escherichia coli , Fenóis/análise , Fenóis/química , Fenóis/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/metabolismo , Extratos Vegetais/farmacologia
10.
Biochem Pharmacol ; 214: 115674, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37414102

RESUMO

Aging contributes to the progressive loss of cellular biological functions and increases the risk of age-related diseases. Cardiovascular diseases, some neurological disorders and cancers are generally classified as age-related diseases that affect the lifespan of individuals. These diseases result from the accumulation of cellular damage and reduced activity of protective stress response pathways, which can lead to inflammation and oxidative stress, which play a key role in the aging process. There is now increasing interest in the therapeutic effects of edible plants for the prevention of various diseases, including those associated with aging. It has become clear that the beneficial effects of these foods are due, at least in part, to the high concentration of bioactive phenolic compounds with low side effects. Antioxidants are the most abundant, and their high consumption in the Mediterranean diet has been associated with slower ageing in humans. Extensive human dietary intervention studies strongly suggest that polyphenol supplementation protects against the development of degenerative diseases, especially in the elderly. In this review, we present data on the biological effects of plant polyphenols in the context of their relevance to human health, ageing and the prevention of age-related diseases.


Assuntos
Fenóis , Polifenóis , Humanos , Idoso , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Estresse Oxidativo , Envelhecimento
11.
Int J Mol Sci ; 24(14)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37511220

RESUMO

A neurodegenerative disease is a pathological condition affecting neurons, condemning them to death [...].


Assuntos
Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/metabolismo , Morte Celular , Neurônios/metabolismo
12.
J Steroid Biochem Mol Biol ; 232: 106345, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37286110

RESUMO

Aging is a complex biological process which can be associated with skeletal muscle degradation leading to sarcopenia. The aim of this study consisted i) to determine the oxidative and inflammatory status of sarcopenic patients and ii) to clarify the impact of oxidative stress on myoblasts and myotubes. To this end, various biomarkers of inflammation (C-reactive protein (CRP), TNF-α, IL-6, IL-8, leukotriene B4 (LTB4)) and oxidative stress (malondialdehyde, conjugated dienes, carbonylated proteins and antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase) as well as oxidized derivatives of cholesterol formed by cholesterol autoxidation (7-ketocholesterol, 7ß-hydroxycholesterol), were analyzed. Apelin, a myokine which contributes to muscle strength, was also quantified. To this end, a case-control study was conducted to evaluate the RedOx and inflammatory status in 45 elderly subjects (23 non-sarcopenic; 22 sarcopenic) from 65 years old and higher. SARCopenia-Formular (SARC-F) and Timed Up and Go (TUG) tests were used to distinguish between sarcopenic and non-sarcopenic subjects. By using red blood cells, plasma and/or serum, we observed in sarcopenic patients an increased activity of major antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) associated with lipid peroxidation and protein carbonylation (increased level of malondialdehyde, conjugated dienes and carbonylated proteins). Higher levels of 7-ketocholesterol and 7ß-hydroxycholesterol were also observed in the plasma of sarcopenic patients. Significant differences were only observed with 7ß-hydroxycholesterol. In sarcopenic patients comparatively to non-sarcopenic subjects, significant increase of CRP, LTB4 and apelin were observed whereas similar levels of TNF-α, IL-6 and IL-8 were found. The increased plasma level of 7-ketocholesterol and 7ß-hydroxycholesterol in sarcopenic patients led us to study the cytotoxic effect of these oxysterols on undifferentiated (myoblasts) and differentiated (myotubes) murine C2C12 cells. With the fluorescein diacetate and sulforhodamine 101 assays, an induction of cell death was observed both on undifferentiated and differentiated cells: the cytotoxic effects were less pronounced with 7-ketocholesterol. In addition, IL-6 secretion was never detected whatever the culture conditions, TNF-α secretion was significantly increased on undifferentiated and differentiated C2C12 cells treated with 7-ketocholesterol- and 7ß-hydroxycholesterol, and IL-8 secretion was increased on differentiated cells. 7-ketocholesterol- and 7ß-hydroxycholesterol-induced cell death was strongly attenuated by α-tocopherol and Pistacia lentiscus L. seed oil both on myoblasts and/or myotubes. TNF-α and/or IL-8 secretions were reduced by α-tocopherol and Pistacia lentiscus L. seed oil. Our data support the hypothesis that the enhancement of oxidative stress observed in sarcopenic patients could contribute, especially via 7ß-hydroxycholesterol, to skeletal muscle atrophy and inflammation via cytotoxic effects on myoblasts and myotubes. These data bring new elements to understand the pathophysiology of sarcopenia and open new perspectives for the treatment of this frequent age-related disease.


Assuntos
Antioxidantes , Sarcopenia , Humanos , Camundongos , Animais , Idoso , Catalase , Apelina/metabolismo , Apelina/farmacologia , Antioxidantes/farmacologia , alfa-Tocoferol/metabolismo , alfa-Tocoferol/farmacologia , Sarcopenia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-8/metabolismo , Estudos de Casos e Controles , Interleucina-6/metabolismo , Leucotrieno B4/metabolismo , Leucotrieno B4/farmacologia , Hidroxicolesteróis/metabolismo , Cetocolesteróis/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase , Biomarcadores/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/metabolismo , Óleos de Plantas/metabolismo , Óleos de Plantas/farmacologia
13.
Molecules ; 28(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37049947

RESUMO

Trans-resveratrol (RSV) is a non-flavonoid polyphenol (stilbene) with numerous biological activities, such as anti-tumor activities. However, RSV is rapidly metabolized, which limits its therapeutic use. The availability of RSV analogues with similar activities for use in vivo is therefore a major challenge. For this purpose, several isomeric analogues of RSV, aza-stilbenes (AZA-ST 1a-g), were synthesized, and their toxicities were characterized and compared to those of RSV on murine N2a neuronal cells using especially flow cytometric methods. All AZA-ST 1a-g have an inhibitory concentration 50 (IC50) between 11.3 and 25 µM when determined by the crystal violet assay, while that of RSV is 14.5 µM. This led to the characterization of AZA-ST 1a-g-induced cell death, compared to RSV, using three concentrations encompassing the IC50s (6.25, 12.5 and 25 µM). For AZA-ST 1a-g and RSV, an increase in plasma membrane permeability to propidium iodide was observed, and the proportion of cells with depolarized mitochondria measured with DiOC6(3) was increased. An overproduction of reactive oxygen species (ROS) was also observed on whole cells and at the mitochondrial level using dihydroethidium and MitoSox Red, respectively. However, only RSV induced a mode of cell death by apoptosis associated with a marked increase in the proportion of cells with condensed and/or fragmented nuclei (12.5 µM: 22 ± 9%; 25 µM: 80 ± 10%) identified after staining with Hoechst 33342 and which are characteristic of apoptotic cells. With AZA-ST, a slight but significant increase in the percentage of apoptotic cells was only detected with AZA-ST 1b (25 µM: 17 ± 1%) and AZA-ST 1d (25 µM: 26 ± 4%). Furthermore, only RSV induced significant cell cycle modifications associated with an increase in the percentage of cells in the S phase. Thus, AZA-ST 1a-g-induced cell death is characterized by an alteration of the plasma membrane, an induction of mitochondrial depolarization (loss of ΔΨm), and an overproduction of ROS, which may or may not result in a weak induction of apoptosis without modification of the distribution of the cells in the different phases of the cell cycle.


Assuntos
Apoptose , Estilbenos , Camundongos , Animais , Resveratrol/farmacologia , Resveratrol/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fase S , Morte Celular , Ciclo Celular , Mitocôndrias/metabolismo , Estilbenos/farmacologia , Estilbenos/metabolismo
14.
Molecules ; 27(24)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36558167

RESUMO

Diabetic nephropathy is manifested in more than 10% of people with diabetes. It is a common cause of kidney failure and end-stage kidney disease. Understanding of mechanisms underlying the initiation and development of diabetes-induced kidney injuries will allow for the development of more effective methods of prevention and treatment of the disease. Diabetic nephropathy is a wide-ranging complication of diabetes, and it is necessary to discuss the "weight" of pro-inflammatory pathways and molecules in the progress of renal injuries during the development of the disease. A large spectrum of pro-inflammatory molecules and pathways participate in different stages of the pathophysiological progression of diabetic nephropathy, including pro-inflammatory cytokines, chemokines, their receptors, adhesion molecules, and transcription factors. On the other hand, it is known that one of the consequences of hyperglycemia-induced ROS generation is the up-regulation of pro-inflammatory cascades, which, in turn, activate the transcription of genes encoding cytokines-chemokines, growth factors, and extracellular matrix proteins. It is a proven fact that a variety of plant secondary metabolites, such as tannins, flavonoids, and other polyphenols, demonstrate significant anti-diabetic, redox-modulating properties and effectively modulate the inflammatory response. Thus, this review is discussing the possible role of plant phenols in the prevention and treatment of diabetic nephropathy.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/etiologia , Taninos/farmacologia , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Polifenóis/metabolismo , Transdução de Sinais , Estresse Oxidativo , Rim , Citocinas/metabolismo , Inflamação/metabolismo , Quimiocinas/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo
15.
Cells ; 11(22)2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36429041

RESUMO

Due to the increase in life span and life expectancy, which can, however, be more or less pronounced depending on the economic, social and cultural context [...].


Assuntos
Cetocolesteróis , Osteogênese , Diferenciação Celular , Longevidade
16.
Steroids ; 187: 109093, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36029811

RESUMO

7-ketocholesterol and 7ß-hydroxycholesterol are two oxysterols mainly formed by the autoxidation of cholesterol. These two molecules are interconvertible via specific enzymes. These two oxysterols are often observed at increased amounts in biological fluids as well as tissues and organs affected during age-related diseases and in diseases of civilization such as cardiovascular, neurodegenerative, and ocular diseases as well as type 2 diabetes and metabolic syndrome. Noteworthy, 7-ketocholesterol and 7ß-hydroxycholesterol induce oxidative stress and inflammation, which are frequently observed in patients with age-related and civilization diseases. For this reason, the involvement of these two oxysterols in the pathophysiology of these diseases is widely suspected. In addition, the toxicity of these oxysterols can lead to death by oxiapoptophagy characterized by oxidative stress, apoptosis induction and autophagy criteria. To prevent, or even treat, certain age-related or civilization diseases associated with increased levels of 7-ketocholesterol and 7ß-hydroxycholesterol, the identification of molecules or mixtures of molecules attenuating or inhibiting the toxic effects of these oxysterols allows to consider new treatments. In this context, many nutrients present in significant amounts in the Mediterranean diet, especially tocopherols, fatty acids, and polyphenols, have shown cytoprotective activities as well as several Mediterranean oils (argan and olive oils, milk thistle seed oil, and pistacia lentiscus seed oil). Consequently, a nutraceutical approach, rich in nutrients present in the Mediterranean diet, could thus make it possible to counteract certain age-related and civilization diseases associated with increased levels of 7-ketocholesterol and 7ß-hydroxycholesterol.


Assuntos
Diabetes Mellitus Tipo 2 , Dieta Mediterrânea , Envelhecimento , Civilização , Ácidos Graxos , Humanos , Hidroxicolesteróis/farmacologia , Cetocolesteróis/farmacologia , Nutrientes , Óleos , Azeite de Oliva , Polifenóis , Tocoferóis
17.
J Oleo Sci ; 71(8): 1117-1133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35922928

RESUMO

The present study provides the fatty acid, tocopherol, phytosterol, and polyphenol profiles of some Mediterranean oils extracted from pumpkin, melon, and black cumin seed oils and those of dietary argan seed oil. Gas chromatography analysis revealed that oleic and linoleic acids were the most abundant fatty acids. Argan and melon seed oils exhibited the highest levels of oleic acid (47.32±0.02%) and linoleic acid (58.35±0.26%), respectively. In terms of tocopherols, melon seed oil showed the highest amount (652.1±3.26 mg/kg) with a predominance of γ-tocopherol (633.1±18.81 mg/kg). The phytosterol content varied between 2237.00±37.55 µg/g for argan oil to 6995.55±224.01 µg/g for melon seed oil. High Performance Liquid Chromatography analysis also revealed the presence of several polyphenols: vanillin (0.59 mg equivalents Quercetin/100 g) for melon seed oil, and p-hydroxycinnamic acid (0.04 mg equivalents Quercetin/100 g), coumarine (0.05 mg equivalents Quercetin/100 g), and thymoquinone (1.2 mg equivalents Quercetin/100 g) for black cumin seed oil. The "Kit Radicaux Libres" (KRL) assay used to evaluate the scavenging properties of the oils showed that black cumin seed oil was the most efficient. On the light of the richness of all Mediterranean oil samples in bioactive compounds, the seed oils studied can be considered as important sources of nutrients endowed with cytoprotective properties which benefits in preventing age-related diseases which are characterized by an enhanced oxidative stress.


Assuntos
Fitosteróis , Tocoferóis , Ácidos Graxos/análise , Nutrientes/análise , Óleos de Plantas/química , Polifenóis/análise , Quercetina , Esteróis/análise , Tocoferóis/análise
18.
Molecules ; 27(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35897887

RESUMO

Trans-resveratrol is a natural polyphenol showing numerous biological properties, especially anti-tumoral and antioxidant activity. Among numerous resveratrol derivatives, aza-stilbenes, which bear an imine bound, show interesting biological activities. In the present study, we synthesized a series of imine analogs of trans-resveratrol (seven aza-stilbenes) following an easy and low-cost procedure of green chemistry. The toxicity of synthesized aza-stilbenes, which is currently unknown, was evaluated on murine neuronal N2a cells, comparatively to trans-resveratrol, by considering: cell density evaluated by staining with sulforhodamine 101; esterase activity, which is a criteria of cell viability, by staining with fluorescein diacetate; and transmembrane mitochondrial potential, which is known to decrease during cell death, by staining with DiOC6(3) using flow cytometry. In addition, the antioxidant activity was quantified with the KRL (Kit Radicaux Libres) assay, the DPPH (2,2'-diphenyl-1-picrylhydrazyl radical) assay and the FRAP (ferric reducing antioxidant power) assay. The PAOT (Pouvoir Antioxidant Total) score was also used. The aza-stilbenes provide different cytotoxic and antioxidant activities, which are either higher or lower than those of trans-resveratrol. Based on their cytotoxic and antioxidant characteristics, all synthesized aza-stilbenes are distinguished from trans-resveratrol.


Assuntos
Antineoplásicos , Estilbenos , Animais , Antineoplásicos/química , Antioxidantes/química , Antioxidantes/farmacologia , Iminas/farmacologia , Camundongos , Resveratrol/farmacologia , Estilbenos/química , Estilbenos/farmacologia
19.
FEBS J ; 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35880408

RESUMO

Maintaining energy balance is essential for survival and health. This physiological function is controlled by the brain, which adapts food intake to energy needs. Indeed, the brain constantly receives a multitude of biological signals that are derived from digested foods or that originate from the gastrointestinal tract, energy stores (liver and adipose tissues) and other metabolically active organs (muscles). These signals, which include circulating nutrients, hormones and neuronal inputs from the periphery, collectively provide information on the overall energy status of the body. In the brain, several neuronal populations can specifically detect these signals. Nutrient-sensing neurons are found in discrete brain areas and are highly enriched in the hypothalamus. In turn, specialized brain circuits coordinate homeostatic responses acting mainly on appetite, peripheral metabolism, activity and arousal. Accumulating evidence shows that hypothalamic microglial cells located at the vicinity of these circuits can influence the brain control of energy balance. However, microglial cells could have opposite effects on energy balance, that is homeostatic or detrimental, and the conditions for this shift are not totally understood yet. One hypothesis relies on the extent of microglial activation, and nutritional lipids can considerably change it.

20.
Nutrients ; 14(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35683996

RESUMO

Coronavirus illness (COVID-19) is an infectious pathology generated by intense severe respiratory syndrome coronavirus 2 (SARS-CoV-2). This infectious disease has emerged in 2019. The COVID-19-associated pandemic has considerably affected the way of life and the economy in the world. It is consequently crucial to find solutions allowing remedying or alleviating the effects of this infectious disease. Natural products have been in perpetual application from immemorial time given that they are attested to be efficient towards several illnesses without major side effects. Various studies have shown that plant extracts or purified molecules have a promising inhibiting impact towards coronavirus. In addition, it is substantial to understand the characteristics, susceptibility and impact of diet on patients infected with COVID-19. In this review, we recapitulate the influence of extracts or pure molecules from medicinal plants on COVID-19. We approach the possibilities of plant treatment/co-treatment and feeding applied to COVID-19. We also show coronavirus susceptibility and complications associated with nutrient deficiencies and then discuss the major food groups efficient on COVID-19 pathogenesis. Then, we covered emerging technologies using plant-based SARS-CoV-2 vaccine. We conclude by giving nutrient and plants curative therapy recommendations which are of potential interest in the COVID-19 infection and could pave the way for pharmacological treatments or co-treatments of COVID-19.


Assuntos
COVID-19 , Antivirais/uso terapêutico , Vacinas contra COVID-19 , Dieta , Humanos , Incidência , Nutrientes , Estresse Oxidativo , SARS-CoV-2
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