Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros












Base de dados
Intervalo de ano de publicação
1.
ACS Bio Med Chem Au ; 4(3): 131-136, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38911910

RESUMO

Phytohormones have significant roles in redox metabolism, inflammatory responses, and cellular survival mechanisms within the microenvironment of the mammalian brain. Herein, we identified the mammalian molecular targets of three representative strigolactone (SL) analogues structurally derived from apocarotenoids and the functional equivalent of plant hormones. All tested SL analogues have an inhibitory effect on NLRP3 inflammasome-mediated IL-1ß release in murine microglial cells. However, IND and EGO10 became prominent among them due to their high potency at low micromolar doses. All SL analogues dose-dependently suppressed the release and expression of proinflammatory factors. For EGO10 and IND, IC50 values for iNOS-associated NO secretion were as low as 1.72 and 1.02 µM, respectively. In silico analyses revealed that (S)-EGO10 interacted with iNOS, NLRP3, and Keap1 ligands with the highest binding affinities among all stereoisomeric SL analogues. Although all compounds were effective in microglial Mox phenotype polarization, 4-Br-debranone exhibited a differential pattern for upregulating Nrf2-driven downstream enzymes.

2.
Bioresour Technol ; 403: 130832, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754558

RESUMO

This study focused on optimizing the production of fermented Spirulina (FS) products using a bioactivity-guided strategy with Lactobacillus helveticus B-4526 and Kluyveromyces marxianus Y-329 in a 3-L bioreactor. Various operating conditions, including aeration rates and pH modes, were tested. While both microorganisms thrived under all conditions, the "cascade" mode, controlling dissolved oxygen, enhanced protein hydrolysis and antioxidant activity, as confirmed by SDS-PAGE and DPPH/TEAC assays, respectively. Screening revealed that "cascade" FS significantly decreased viability of colon cancer cells (HT-29) in a dose-dependent manner, with up to a 72 % reduction. Doses ≤ 500 µg mL-1 of "cascade" FS proved safe and effective in suppressing NO release without compromising cellular viability. Additionally, "cascade" FS exhibited diverse volatile organic compounds and reducing the characteristic "seaweed" aroma. These findings highlight "cascade" FS as a promising alternative food source with improved bioactive properties, urging further exploration of its bioactive compounds, particularly bioactive peptides.


Assuntos
Reatores Biológicos , Fermentação , Kluyveromyces , Lactobacillus helveticus , Spirulina , Kluyveromyces/metabolismo , Lactobacillus helveticus/metabolismo , Spirulina/metabolismo , Humanos , Sobrevivência Celular/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Células HT29 , Concentração de Íons de Hidrogênio , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/farmacologia
3.
J Cancer Res Clin Oncol ; 149(5): 2095-2113, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35876951

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently prescribed drug classes with wide therapeutic applications over the centuries. Starting from the use of salicylate-containing willow leaves to the recent rise and fall of highly selective cyclooxygenase-2 (COX-2) inhibitors and the latest dual-acting anti-inflammatory molecules, they have displayed a rapid and ongoing evolution. Despite the enormous advances in the last twenty years, investigators are still in search of the design and development of more potent and safer therapy against inflammatory conditions. This challenge has been increasingly attractive as the emergence of inflammation as a common seed and unifying mechanism for most chronic diseases. Indeed, this fact put the NSAIDs in the spotlight for repurposing against inflammation-related disorders. This review attempts to present a historical perspective on the evolution of NSAIDs, regarding their COX-dependent/independent mode of actions, structural and mechanism-based classifications, and adverse effects. Additionally, a systematic review of previous studies was carried out to show the current situation in drug repurposing, particularly in cancers associated with the GI tract such as gastric and colorectal carcinoma. In the case of non-GI-related cancers, preclinical studies elucidating the effects and modes of action were collected and summarized.


Assuntos
Reposicionamento de Medicamentos , Neoplasias , Humanos , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Inflamação/induzido quimicamente , Neoplasias/tratamento farmacológico
4.
ACS Chem Neurosci ; 13(5): 572-580, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35138812

RESUMO

Strigolactones (SLs), carotenoid-derived phytohormones, control the plant response and signaling pathways for stressful conditions. In addition, they impact numerous cellular processes in mammalians and present new scaffolds for various biomedical applications. Recent studies demonstrated that SLs possess potent antitumor activity against several cancer cells. Herein, we sought to elucidate the inhibitory effects of SL analogs on the growth and survival of human brain tumor cell lines. Among four tested SLs, we showed for the first time that two lead bioactiphores, indanone-derived SL and EGO10, can inhibit cancer cell proliferation, induce apoptosis, and induce G1 cell cycle arrest at low concentrations. SL analogs were marked by increased expression of Bax/Caspase-3 genes and downregulation of Bcl-2. In silico studies were conducted to identify drug-likeness, blood-brain barrier penetrating properties, and molecular docking with Bcl-2 protein. Taken together, this study indicates that SLs may be promising antiglioma agents, presenting novel pharmacophores for further preclinical and clinical assessment.


Assuntos
Glioblastoma , Animais , Glioblastoma/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Lactonas/farmacologia , Simulação de Acoplamento Molecular
5.
Plant Foods Hum Nutr ; 77(1): 51-61, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34850338

RESUMO

Morus nigra L. (black mulberry-BM) is a promising nutraceutical fruit containing biologically active polyphenols like anthocyanins, proanthocyanidins, catechins, and stilbenes, with well-established anti-inflammatory, antidiabetic, anti-obesity, and anticancer biofunctions. However, these health-promoting properties in raw fruit are greatly masked due to the presence of soluble and insoluble carbohydrates in excess amounts restricting daily intake of the required dose to achieve targeted effects. In the current study, different protein sources (defatted whey and chickpea flours) were optimized through different conditions to capture polyphenols from BM juice while diminishing its glucose content. To optimize polyphenol-protein interactions, various pHs (3.7, 4.2, and 4.7), matrix concentrations (20, 50, and 80 g protein/L), and incubation times (5, 20, and 45 min) were tested. In the present work, optimized BM polyphenol enriched whey matrix inhibited pro-inflammatory mediators and promoted Nrf-2 dependent cytoprotective enzyme expressions in lipopolysaccharide (LPS) induced macrophages at low doses. In addition, whey proteins were also subjected to an enzymatic deglycosylation process by using recently identified EndoBI-1 enzyme for the specific cleavage of N-glycan core in all glycan types including high mannoses, hybrids as well as complex glycans found on defatted whey proteins. After this process, the polyphenol sorption capacity of deglycosylated whey proteins was found to be significantly higher (37%) than the capacity of non-treated normal whey protein under optimized conditions. In conclusion, deglycosylation of protein matrices could be a novel strategy for efficient sorption/concentration of polyphenols from fruits and vegetables, however, more detailed studies are needed to understand this effect.


Assuntos
Cicer , Morus , Antocianinas/análise , Frutas/química , Polifenóis/análise , Soro do Leite/química , Proteínas do Soro do Leite
6.
Oxid Med Cell Longev ; 2021: 1987588, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594472

RESUMO

Luteolin is a naturally occurring secondary metabolite belonging to the class of flavones. As many other natural flavonoids, it is often found in combination with glycosides in many fruits, vegetables, and plants, contributing to their biological and pharmacological value. Many preclinical studies report that luteolin present excellent antioxidant, anticancer, antimicrobial, neuroprotective, cardioprotective, antiviral, and anti-inflammatory effects, and as a consequence, various clinical trials have been designed to investigate the therapeutic potential of luteolin in humans. However, luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored. Pharmacological potential of luteolin in various disorders has also been underlined, but to some of them, the exact mechanism is still poorly understood. Given the great potential of this natural antioxidant in health, this review is aimed at providing an extensive overview on the in vivo pharmacological action of luteolin and at stressing the main features related to its bioavailability, absorption, and metabolism, while essential steps determine its absolute health benefits and safety profiles. In addition, despite the scarcity of studies on luteolin bioavailability, the different drug delivery formulations developed to increase its bioavailability are also listed here.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Luteolina/farmacocinética , Sepse/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Portadores de Fármacos/química , Humanos , Luteolina/química , Luteolina/farmacologia , Luteolina/uso terapêutico , Fagocitose/efeitos dos fármacos
7.
Front Pharmacol ; 12: 674682, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504422

RESUMO

Sexually transmitted diseases (STDs) are produced by pathogens like bacteria, fungi, parasites, and viruses, and may generate severe health problems such as cancer, ulcers, and even problems in the newborn. This narrative review aims to present updated information about the use of natural bioactive compounds for the prevention and treatment of sexually transmitted infections. A search of the literature was performed using databases and search engines such as PubMed, Scopus, Google Scholar and Science Direct. From the pharmacotherapeutic management point of view, any strategies for prevention should contain medical approaches. The bioactive compounds obtained from natural products have shown biological effects against different microorganisms for the treatment of these diseases. The main results showed antimicrobial, antiprotozoal, antifungal and antiviral effects such as HIV. Also, the molecular mechanisms, signalling pathways and action targets of natural compounds were highlighted, thus justifying bacterial and antifungal inhibition, apoptosis or reduction of viral replication. From the data of our study, we can conclude that natural compounds may be a significant source for adjuvant drugs / complementary therapies in the treatment of STDs. With all these benefits, the future must conduct extensive clinical trials and the development of pharmaceutical nanotechnologies for a greater therapeutic effect.

8.
Oxid Med Cell Longev ; 2021: 1917890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512863

RESUMO

The genus Diplazium (family: Athyriaceae) comprises approximately 350 species of pteridophytes. Diplazium esculentum (Retz.) Sw. is an important member of this genus and commonly known as a wild vegetable in the Himalayan and sub-Himalayan communities. According to the literature analysis, D. esculentum was traditionally used for the prevention or treatment of several diseases such as diabetes, smallpox, asthma, diarrhea, rheumatism, dysentery, headache, fever, wounds, pain, measles, hypertension, constipation, oligospermia, bone fracture, and glandular swellings. Various extracts of D. esculentum were evaluated to elucidate their phytochemical and pharmacological activities. A wide array of pharmacological properties such as antioxidant, antimicrobial, antidiabetic, immunomodulatory, CNS stimulant, and antianaphylactic activities have been recognized in different parts of D. esculentum. The review covers a systematic examination of pharmacognosy, phytochemistry, and pharmacological applications of D. esculentum, but scientifically, it is not fully assessed regarding complete therapeutic effects, toxicity, and safety in the human body. The published literature on D. esculentum and its therapeutic properties were collected from different search engines including Wiley online, PubMed, Springer Link, Scopus, Science Direct, Web of Science, Google Scholar, and ACS publications by using specific terms such as "Diplazium esculentum, bioactive compounds, biological activities and health benefits" from 1984 to 2021 (March). Therefore, further studies are required to identify the detailed action mechanism of D. esculentum in vitro/in vivo, and also, more studies should focus on conservation, cultivation, and sustainable utilization of the species.


Assuntos
Gleiquênias/química , Medicina Tradicional/métodos , Humanos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
9.
Eur J Med Chem ; 221: 113566, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34077833

RESUMO

Seventeen new amide/sulfonamide containing nimesulide derivatives were synthesized and characterized by several spectroscopic techniques and primarily investigated for their inhibitory potential on COX enzymes and other pro-inflammatory factors. Experimental analyses showed that among seventeen compounds, N8 and N10 have remarkable potency and selectivity for the COX-2 enzyme over COX-1 at very low doses as compared to nimesulide. Moreover, both N8 and N10 selectively reduced the Lipopolysaccharide (LPS)-stimulated COX-2 mRNA expression level while the COX-1 level remained stable. Both PGE2 release and nitric oxide production in macrophage cells were significantly suppressed by the N8 and N10 treatment groups. In silico ADME/Tox, molecular docking and molecular dynamics (MD) simulations were also conducted. Additionally, all compounds were also screened in a panel of cancer cell lines for their antiproliferative properties by MTT and SRB assays. Compound N17 exhibited a considerable antiproliferative effect on the colon (IC50: 9.24 µM) and breast (IC50: 11.35 µM) cancer cell lines. N17 exposure for 48 h decreased expression of anti-apoptotic protein BCL-2 and increased the expression of apoptogenic BAX. Besides, the BAX/BCL-2 ratio was increased with visible ultrastructural changes and apoptotic bodies under scanning electron microscopy. In order to investigate the structural and dynamical properties of selected hits on the target structures, multiscale molecular modeling studies are also conducted. Our combined in silico and in vitro results suggest that N8 and N10 could be further developed as potential nonsteroidal anti-inflammatory drugs (NSAIDs), while cytotoxic N17 might be studied as a potential lead compound that could be developed as an anticancer agent.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Sulfonamidas/farmacologia , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química
10.
Neurochem Res ; 46(9): 2205-2225, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34120291

RESUMO

Epilepsy is a related chronic neurological condition of a predisposition for recurrent epileptic seizures, with various manifestations and causes. Although there are antiepileptic drugs, complementary natural therapies are widely used. The purpose of this systematic review was to analyze the antiepileptic/anticonvulsant pharmacological properties of plant-food derived bioactive molecules. In this regard, a systematic review of the PubMed database was made based on the inclusion criteria. Natural compounds/herbs with scientifically proven antiepileptic properties were selected. Experimental pharmacological studies in vitro and in vivo have shown that flavonoids, alkaloids and terpenoids may have anticonvulsant mechanisms similar to the new generation antiepileptic drugs. The relationships of structure-anticonvulsant effect, pharmacological models, seizure-inducing factors and response, effective dose were also analyzed and discussed. The results of in vitro and in vivo pharmacological studies analyzed in this systematic review support the clinical importance of plant-food-derived bioactive molecules for the complementary treatment of epilepsy. Thus, are opened new perspectives to develop new natural anticonvulsant drugs.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Convulsões/tratamento farmacológico , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Animais , Anticonvulsivantes/farmacologia , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Terpenos/uso terapêutico
11.
Data Brief ; 35: 106786, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33553532

RESUMO

When THP-1 cells are differentiated into adherent macro-phage-like cells, they respond to inflammatory stimuli by changing their phenotypes to an activation state and altering the expression of inflammation-related genes. Nitric oxide (NO) is a diatomic molecule implicating in various pathological conditions including tissue damage, ER stress, obesity, and cancer. The sustained inflammatory microenvironment leads to increased NO release through the activation of the inducible nitric oxide synthase (iNOS) gene in macrophages. Here, we provide a dataset on the optimized conditions for the THP-1 differentiation and the induction of NO/iNOS signaling under inflammatory stimulus. The human monocytic cells were differentiated into adherent macrophage-like phenotype by phorbol-12-myristate-13-acetate (PMA) stimulation under optimized conditions. In this study, NO/iNOS signaling capacity and the regulation of other pro-inflammatory genes including TNF-α, IL-1ß, and COX-2 in the LPS-induced THP-1 were examined.

12.
Phytother Res ; 35(1): 95-121, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32789910

RESUMO

Origanum species are mostly distributed around the Mediterranean, Euro-Siberian, and Iran-Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name "oregano" or "pizza-spice." Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p-cymen and -terpinene) or of terpinene-4-ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti-obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure-activity studies are needed to explore the potential use of Origanum-derived phytochemicals as promising drug candidates.


Assuntos
Óleos Voláteis/química , Origanum/química , Compostos Fitoquímicos/química , Humanos
13.
J Clin Med ; 9(4)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276438

RESUMO

Among the major neurodegenerative disorders (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD), are a huge socioeconomic burden. Over many centuries, people have sought a cure for NDDs from the natural herbals. Many medicinal plants and their secondary metabolites are reported with the ability to alleviate the symptoms of NDDs. The major mechanisms identified, through which phytochemicals exert their neuroprotective effects and potential maintenance of neurological health in ageing, include antioxidant, anti-inflammatory, antithrombotic, antiapoptotic, acetylcholinesterase and monoamine oxidase inhibition and neurotrophic activities. This article review the mechanisms of action of some of the major herbal products with potential in the treatment of NDDs according to their molecular targets, as well as their regional sources (Asia, America and Africa). A number of studies demonstrated the beneficial properties of plant extracts or their bioactive compounds against NDDs. Herbal products may potentially offer new treatment options for patients with NDDs, which is a cheaper and culturally suitable alternative to conventional therapies for millions of people in the world with age-related NDDs.

14.
ACS Chem Neurosci ; 11(4): 501-507, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32017526

RESUMO

Neuropathological changes in Alzheimer's disease (AD) are directly linked to the early inflammatory microenvironment in the brain. Therefore, disease-modifying agents targeting neuroinflammation may open up new avenues in the treatment of AD. Strigolactones (SLs), subclasses of structurally diverse and biologically active apocarotenoids, have been recently identified as novel phytohormones. In spite of the remarkable anticancer capacity shown by SLs, their effects on the brain remained unexplored. Herein, the SIM-A9 microglial cell line was used as a phenotypic screening tool to search for the representative SL, GR24, demonstrating marked potency in the suppression of lipopolysaccharide (LPS)-induced neuroinflammatory/neurotoxic mediators by regulating NF-κB, Nrf2, and PPARγ signaling. GR24 also in the brain endothelial cell line bEnd.3 mitigated the LPS-increased permeability as evidenced by reduced Evans' blue extravasation through enhancing the expression of tight junction protein, occludin. Collectively, the present work shows the anti-neuroinflammatory and glia/neuroprotective properties of GR24, making SLs promising scaffolds for the development of novel anti-AD candidates.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Inflamação/metabolismo , Microglia/metabolismo , Animais , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Molecules ; 24(7)2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30959974

RESUMO

Piper species are aromatic plants used as spices in the kitchen, but their secondary metabolites have also shown biological effects on human health. These plants are rich in essential oils, which can be found in their fruits, seeds, leaves, branches, roots and stems. Some Piper species have simple chemical profiles, while others, such as Piper nigrum, Piper betle, and Piper auritum, contain very diverse suites of secondary metabolites. In traditional medicine, Piper species have been used worldwide to treat several diseases such as urological problems, skin, liver and stomach ailments, for wound healing, and as antipyretic and anti-inflammatory agents. In addition, Piper species could be used as natural antioxidants and antimicrobial agents in food preservation. The phytochemicals and essential oils of Piper species have shown strong antioxidant activity, in comparison with synthetic antioxidants, and demonstrated antibacterial and antifungal activities against human pathogens. Moreover, Piper species possess therapeutic and preventive potential against several chronic disorders. Among the functional properties of Piper plants/extracts/active components the antiproliferative, anti-inflammatory, and neuropharmacological activities of the extracts and extract-derived bioactive constituents are thought to be key effects for the protection against chronic conditions, based on preclinical in vitro and in vivo studies, besides clinical studies. Habitats and cultivation of Piper species are also covered in this review. In this current work, available literature of chemical constituents of the essential oils Piper plants, their use in traditional medicine, their applications as a food preservative, their antiparasitic activities and other important biological activities are reviewed.


Assuntos
Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Piper/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Ecossistema , Conservação de Alimentos , Medicina Tradicional , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Piper/classificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia
17.
Comput Biol Chem ; 76: 179-190, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30048925

RESUMO

Naturally occurring phytohormones have shown distinguished potential in chemoprevention and treatment of chronic inflammatory diseases in mammalian cells. Strigolactones (SLs) are a class of carotenoid-derived lactones regulating many aspects of plant development and recently recognized as phytohormones with promising anticancer activity. In this study, GR24, a synthetic analog and representative of SLs, induced the expression of phase II detoxifying enzymes such as HO-1 and NQO1 in hepatic and macrophage cell lines under normal and inflammatory conditions, respectively. This effect has been found to be mediated by Nrf2 activation. In silico molecular docking against 16-mer peptide binding site on Keap1 suggested that GR24 may exert its biological activity by interfering with Keap1 and Nrf2 binding. GR24 also displayed remarkably potent inhibitory activity against the production of nitric oxide (NO) and molecular docking analysis on iNOS supported experimental data. Furthermore, GR24 dose dependently suppressed the LPS-induced iNOS expression at both mRNA and protein level. It also significantly decreased IL-1ß release, mRNA expression of IL-1ß and COX-2, as well as nuclear accumulation of NFÒ¡B at the low micro molar range in LPS-stimulated murine macrophages. GR24 promoted AKT activation in insulin resistant skeletal muscle cells and downregulated the expression of enzymes, PEPCK and G6Pase control the rate limiting steps of gluconeogenesis in hepatic cells. The results of molecular docking and ADMET analyses indicated that GR24 might be classified as druggable molecule in drug design. Taken together, all results suggest that SLs can be promising multi-potent botanical leads for the mitigation of inflammatory-mediated chronic disorders.


Assuntos
Inflamação/metabolismo , Lactonas/farmacologia , Fator 2 Relacionado a NF-E2/agonistas , Animais , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Ativadores de Enzimas/química , Ativadores de Enzimas/farmacologia , Gluconeogênese/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/química , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lactonas/química , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Mioblastos/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/química , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células RAW 264.7 , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Regulação para Cima
18.
Toxicol Ind Health ; 32(12): 1942-1951, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26381689

RESUMO

In this study, we aimed to investigate the extent of genotoxic risk and the association between null GSTM1/GSTT1 and GSTP1 Ile105Val variants and cellular DNA damage, as measured by micronucleus (MN) assay in a group of agricultural workers from Denizli, Turkey. Peripheral blood samples were collected from 116 subjects, including 58 workers who were occupationally exposed to pesticides and 58 healthy unexposed controls. The MN frequencies of each individual were assessed by cytokinesis-blocked micronuclei assays on lymphocytes. Genotypes for different GST variants were determined using polymerase chain reaction-based methods. A significant 3.4-fold increase in MN frequency was observed in workers compared with the controls (p < 0.001). Among the GST genotypes, only the GSTM1 null genotype was found to be significantly associated with an increased MN frequency in workers (p = 0.01). Individuals with a concomitant null GSTM1/GSTT1 genotype demonstrated a significant (p = 0.01) increase in MN frequency compared with those with functional isozymes in the exposed worker group. The association of the GSTM1 null genotype with higher MN frequency suggests that it may be a modifier of genotoxic risk in individuals exposed to pesticides and may thus be a candidate susceptibility biomarker for human biomonitoring studies.


Assuntos
Fazendeiros , Glutationa Transferase/genética , Testes para Micronúcleos , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Adulto , Estudos de Casos e Controles , Dano ao DNA , Monitoramento Ambiental , Feminino , Frequência do Gene , Marcadores Genéticos , Genótipo , Técnicas de Genotipagem , Glutationa S-Transferase pi/genética , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Praguicidas/sangue , Turquia , Adulto Jovem
19.
Mol Nutr Food Res ; 59(6): 1013-24, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25620073

RESUMO

SCOPE: Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. METHODS AND RESULTS: C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1ß, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. CONCLUSION: Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.


Assuntos
Fármacos Antiobesidade/farmacologia , Gluconeogênese/efeitos dos fármacos , Resistência à Insulina , Isotiocianatos/farmacologia , Moringa oleifera/química , Aumento de Peso/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Composição Corporal , Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica , Fígado Gorduroso/prevenção & controle , Glucose-6-Fosfatase/sangue , Hipoglicemiantes/farmacologia , Insulina/sangue , Interleucina-1beta/sangue , Leptina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Resistina/sangue , Fator de Necrose Tumoral alfa/sangue
20.
J Agric Food Chem ; 63(5): 1505-13, 2015 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-25605589

RESUMO

Moringa oleifera Lam. is a fast-growing, tropical tree with various edible parts used as nutritious food and traditional medicine. This study describes an efficient preparatory strategy to extract and fractionate moringa leaves by fast centrifugal partition chromatography (FCPC) to produce polyphenol and isothiocyanate (ITC) rich fractions. Characterization and further purification of these fractions showed that moringa polyphenols were potent direct antioxidants assayed by oxygen radical absorbance capacity (ORAC), whereas moringa ITCs were effective indirect antioxidants assayed by induction of NAD(P)H quinone oxidoreductase 1 (NQO1) activity in Hepa1c1c7 cells. In addition, purified 4-[(α-l-rhamnosyloxy)benzyl]isothiocyanate and 4-[(4'-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate were further evaluated for their ORAC and NQO1 inducer potency in comparison with sulforaphane (SF). Both ITCs were as potent as SF in inducing NQO1 activity. These findings suggest that moringa leaves contain a potent mixture of direct and indirect antioxidants that can explain its various health-promoting effects.


Assuntos
Antioxidantes/química , Isotiocianatos/química , Moringa oleifera/química , Extratos Vegetais/química , Polifenóis/química , Animais , Antioxidantes/isolamento & purificação , Linhagem Celular , Isotiocianatos/isolamento & purificação , Camundongos , NAD(P)H Desidrogenase (Quinona)/análise , NAD(P)H Desidrogenase (Quinona)/metabolismo , Extratos Vegetais/isolamento & purificação , Polifenóis/isolamento & purificação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...