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1.
Food Res Int ; 188: 114415, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823855

RESUMO

Several scientific studies have warned that the ingestion of dietary lipid oxidation products (LOPs) may initiate or exacerbate the development of several chronic non-communicable diseases in humans. Indeed, the constantly increasing consumption of culinary oils by larger global populations indicates the need for scientific techniques to suppress the evolution of LOPs in thermo-oxidised oils. This study employed a 600.13 MHz frequency NMR spectrometer in evaluating the effect of 10, 50, and 100 ppm concentrations of chemical compounds reported to have antioxidant properties in continuously-stirred and thermally stressed polyunsaturated fatty acid (PUFA)-rich hemp seed oil at a frying temperature of 180℃ for 180 min. Research data acquired showed that the antioxidants α- and γ-tocopherol, γ-oryzanol, ß-carotene, eugenol, resveratrol, ascorbyl palmitate, gentisic acid, and L-ascorbic acid all played a vital role in suppressing the evolution of secondary aldehydic lipid oxidation products in hemp seed oil. However, the most ineffective LOP-suppressing agent was L-lysine, an observation which may be accountable by its poor oil solubility. Nonetheless, trends deduced for compounds acting as antioxidants were mainly unique for each class of agent tested. Conversely, the antioxidant capacity of resveratrol was consistently higher, and this effect was found to be independent of its added amounts. This report provides a direct approach in developing scientific methods for the suppression of LOPs in thermo-oxidatively susceptible PUFA-rich cooking oils.


Assuntos
Antioxidantes , Cannabis , Temperatura Alta , Peroxidação de Lipídeos , Óleos de Plantas , Antioxidantes/química , Óleos de Plantas/química , Cannabis/química , Peroxidação de Lipídeos/efeitos dos fármacos , Culinária , Sementes/química , Resveratrol/química , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/química , Espectroscopia de Ressonância Magnética , Ácido Ascórbico/química , Extratos Vegetais
2.
Food Res Int ; 188: 114485, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823871

RESUMO

Whey protein isolate (WPI) is mainly composed of ß-lactoglobulin (ß-LG), α-lactalbumin (α-LA) and bovine serum albumin (BSA). The aim of this study was to compare and analyze the influence of WPI and its three main constituent proteins, as well as proportionally reconstituted WPI (R-WPI) on resveratrol. It was found that the storage stability of resveratrol was protected by WPI, not affected by R-WPI, but reduced by individual whey proteins at 45°C for 30 days. The rank of accelerated degradation of resveratrol by individual whey proteins was BSA > α-LA > ß-LG. The antioxidant activity, localization of resveratrol and oxidation of carrier proteins were determined by ABTS, H2O2 assay, synchronous fluorescence, carbonyl and circular dichroism. The non-covalent interactions and disulfide bonds between constituent proteins improved the antioxidant activity of the R-WPI-resveratrol complex, the oxidation stability of the carrier and the solvent shielding effect on resveratrol, which synergistically inhibited the degradation of resveratrol in R-WPI system. The results gave insight into elucidating the interaction mechanism of resveratrol with protein carriers.


Assuntos
Antioxidantes , Lactalbumina , Lactoglobulinas , Oxirredução , Resveratrol , Soroalbumina Bovina , Proteínas do Soro do Leite , Resveratrol/química , Resveratrol/farmacologia , Proteínas do Soro do Leite/química , Lactalbumina/química , Antioxidantes/química , Antioxidantes/farmacologia , Lactoglobulinas/química , Soroalbumina Bovina/química , Dicroísmo Circular
3.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 28-36, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836684

RESUMO

Piceatannol, resveratrol's derivative, and a valuable polyphenol has managed to become one of the most remarkable candidate molecules for drug development research, with its high bioactive properties and higher stability. On the other hand, the very low amount of piceatannol in plants which are its natural source increases the cost and limits the commercialization possibilities of the product. To overcome this bottleneck, a limited number of studies have recently shown that it is possible to produce piceatannol from the resveratrol precursor much cheaper by regioselective hydroxylation catalyzed by bacteria isolated from the soil, and the search for new bacteria of similar nature in new ecosystems has gained popularity. The aim of our study, which was prepared within this framework, is the bacterial isolate with regioselective hydroxylation potential obtained as a result of selective isolation steps; determination of resveratrol hydroxylation potentials and piceatannol product yields, investigation of possibilities to increase piceatannol yield with optimization trials and identification of isolates with the highest yield. For this purpose, 200 bacterial isolates capable of resveratrol hydroxylation were obtained from soil samples taken from Erzurum (Turkey) and its surroundings by using selective media. In the continuation of the study; resveratrol hydroxylation trials were carried out with these isolates and 55 active isolates capable of producing piceatannol by regioselective hydroxylation were selected. Then, yield improvement studies of active isolates were carried out by using different carbon sources and optimizing the culture conditions. As a result, a culture collection was created by identifying the 6 most active bacterial isolates with commercialization potential using conventional and molecular methods. These are 4 Gram-positive (Rhodococcus sp., Rhodococcus erythropolis, Paeniglutamicibacter sp., Arthrobacter sp.) and 2 Gram-negative (Shinella sp., Ensifer adhaerens) bacterial isolates. As a result of the optimization studies, three of these isolates used phenol as a biocatalyst, while the other three increased the production yield of piceatannol by using 4-hydroxyphenylacetic acid.


Assuntos
Bactérias , Resveratrol , Microbiologia do Solo , Estilbenos , Estilbenos/metabolismo , Estilbenos/isolamento & purificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/classificação , Resveratrol/metabolismo , Turquia , Hidroxilação
4.
Med Oncol ; 41(7): 167, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831079

RESUMO

Cancer stem cells (CSCs) are mainly responsible for tumorigenesis, chemoresistance, and cancer recurrence. CSCs growth and progression are regulated by multiple signaling cascades including Wnt/ß-catenin and Hh/GLI-1, which acts independently or via crosstalk. Targeting the crosstalk of signaling pathways would be an effective approach to control the CSC population. Both Wnt/ß-catenin and Hh/GLI-1 signaling cascades are known to be regulated by p53/p21-dependent mechanism. However, it is interesting to delineate whether p21 can induce apoptosis in a p53-independent manner. Therefore, utilizing various subtypes of oral CSCs (SCC9-PEMT p53+/+p21+/+, SCC9-PEMT p53-/-p21+/+, SCC9-PEMT p53+/+p21-/- and SCC9-PEMT p53-/-p21-/-), we have examined the distinct roles of p53 and p21 in Resveratrol nanoparticle (Res-Nano)-mediated apoptosis. It is interesting to see that, besides the p53/p21-mediated mechanism, Res-Nano exposure also significantly induced apoptosis in oral CSCs through a p53-independent activation of p21. Additionally, Res-Nano-induced p21-activation deregulated the ß-catenin-GLI-1 complex and consequently reduced the TCF/LEF and GLI-1 reporter activities. In agreement with in vitro data, similar experimental results were obtained in in vivo mice xenograft model.


Assuntos
Apoptose , Inibidor de Quinase Dependente de Ciclina p21 , Neoplasias Bucais , Nanopartículas , Células-Tronco Neoplásicas , Resveratrol , Proteína Supressora de Tumor p53 , Proteína GLI1 em Dedos de Zinco , beta Catenina , Apoptose/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Resveratrol/farmacologia , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , beta Catenina/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Animais , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Camundongos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Molecules ; 29(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38731555

RESUMO

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering -3.31, -1.68, and -6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states' properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated.


Assuntos
Antocianinas , Teoria da Densidade Funcional , Resveratrol , Antocianinas/química , Resveratrol/química , Termodinâmica , Modelos Moleculares , Água/química
6.
J Transl Med ; 22(1): 457, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745204

RESUMO

BACKGROUND AND PURPOSE: Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway. METHODS: We established an arthritis model by combining chicken type II collagen and complete Freund's adjuvant. Resveratrol treatment was administered via tube feeding for 10 days. Pathological changes in both the joints and lungs were evaluated using HE and Masson staining techniques. Protein expression of TGF-ß1, AKT, and TMEM175 was examined in lung tissue. MRC-5 cells were stimulated using IL-1ß in combination with TGF-ß1 as an in vitro model of RA-ILD, and agonists of AKT, metabolic inhibitors, and SiRNA of TMEM175 were used to explore the regulation and mechanism of action of resveratrol RA-ILD. RESULTS: Resveratrol mitigates fibrosis in rheumatoid arthritis-associated interstitial lung disease and reduces oxidative stress and inflammation in RA-ILD. Furthermore, resveratrol restored cellular autophagy. When combined with the in vitro model, it was further demonstrated that resveratrol could suppress TGF-ß1 expression, and reduce AKT metamorphic activation, consequently inhibiting the opening of AKT/MEM175 ion channels. This, in turn, lowers lysosomal pH and enhances the fusion of autophagosomes with lysosomes, ultimately ameliorating the progression of RA-ILD. CONCLUSION: In this study, we demonstrated that resveratrol restores autophagic flux through the AKT/MEM175 pathway to attenuate inflammation as well as fibrosis in RA-ILD by combining in vivo and in vitro experiments. It further provides a theoretical basis for the selection of therapeutic targets for RA-ILD.


Assuntos
Artrite Reumatoide , Fibrose , Inflamação , Doenças Pulmonares Intersticiais , Proteínas Proto-Oncogênicas c-akt , Resveratrol , Transdução de Sinais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/metabolismo , Humanos , Inflamação/patologia , Inflamação/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Proteínas de Membrana/metabolismo , Autofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Pulmão/patologia , Pulmão/efeitos dos fármacos , Masculino
7.
BMC Cancer ; 24(1): 566, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711004

RESUMO

BACKGROUND: Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells. METHODS: Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay. RESULTS: The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer. CONCLUSIONS: In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells.


Assuntos
Proteína BRCA1 , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Regiões Promotoras Genéticas , Resveratrol , Neoplasias de Mama Triplo Negativas , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Humanos , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico
8.
Cryo Letters ; 45(4): 240-247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38809788

RESUMO

BACKGROUND: Vitrification is a technique of cryopreservation that has been proposed as a promising alternative method for the preservation of oocytes, embryos and gonadal tissue. OBJECTIVE: To determine the effect of different antioxidants on post-thaw viability, morphology of retrieved oocytes and histology of vitrified ovarian tissue. MATERIALS AND METHODS: Four different antioxidants [i.e., resveratrol (20 uM), ZnSO4 (500 uM), curcumin (25 uM) and quercetin (1 uM)] were evaluated after their addition to the vitrification and warming media for their effects on the viability and morphology of retrieved oocytes and the histology of vitrified ovarian tissue. RESULTS: The number of oocytes retrieved from ovarian tissue from the above mentioned antioxidants and vitrified control were 34, 41, 26, 31 and 46 respectively. Among these the number of viable oocytes were found to be 24 (70.6%), 30 (73.1 %), 20 (76.9%), 26 (83.9%) and 33 (71.7%) and the number of oocytes found morphologically normal were 24 (70.6%), 26 (63.4%), 18 (69.2%), 21 (67.7%) and 34 (73.9%) for the above mentioned different antioxidants and vitrified control, respectively. Non-significant (P. > 0.05) differences were found between different treatment groups. Histomorphological evaluation of the ovarian cortical tissue showed that the percentage of intact follicles was significantly (P < 0.05) higher in the fresh control (84.19±3.9) than in other groups. Non-significant differences were found between resveratrol (50.2±5.5), curcumin (48.7±5.7), quercetin (51.6±4.8) and the vitrified control (42.7±6.1) groups; however, the ZnSO4 supplemented group (23.1±8.54) differed significantly (P < 0.05) from other antioxidant groups but was non-significant (P > 0.05) with the vitrified control group (42.7±6.1). CONCLUSION: The addition of antioxidants resveratrol, curcumin and quercetin at these concentrations tended to non-significantly improve the follicular integrity after vitrification. Doi.org/10.54680/fr24410110212.


Assuntos
Antioxidantes , Criopreservação , Crioprotetores , Curcumina , Oócitos , Ovário , Quercetina , Resveratrol , Vitrificação , Vitrificação/efeitos dos fármacos , Feminino , Antioxidantes/farmacologia , Animais , Criopreservação/métodos , Criopreservação/veterinária , Quercetina/farmacologia , Ovário/efeitos dos fármacos , Resveratrol/farmacologia , Curcumina/farmacologia , Oócitos/efeitos dos fármacos , Oócitos/citologia , Oócitos/fisiologia , Crioprotetores/farmacologia , Ovinos , Sulfato de Zinco/farmacologia , Sobrevivência Celular/efeitos dos fármacos
9.
Nutrients ; 16(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38732545

RESUMO

Natural products from mushrooms, plants, microalgae, and cyanobacteria have been intensively explored and studied for their preventive or therapeutic potential. Among age-related pathologies, neurodegenerative diseases (such as Alzheimer's and Parkinson's diseases) represent a worldwide health and social problem. Since several pathological mechanisms are associated with neurodegeneration, promising strategies against neurodegenerative diseases are aimed to target multiple processes. These approaches usually avoid premature cell death and the loss of function of damaged neurons. This review focuses attention on the preventive and therapeutic potential of several compounds derived from natural sources, which could be exploited for their neuroprotective effect. Curcumin, resveratrol, ergothioneine, and phycocyanin are presented as examples of successful approaches, with a special focus on possible strategies to improve their delivery to the brain.


Assuntos
Curcumina , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Resveratrol , Fármacos Neuroprotetores/farmacologia , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/prevenção & controle , Curcumina/farmacologia , Resveratrol/farmacologia , Ergotioneína/farmacologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Ficocianina/farmacologia , Animais , Cianobactérias , Agaricales/química , Microalgas
10.
Mech Ageing Dev ; 219: 111938, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744411

RESUMO

Progressive liver disease and dysfunction cause toxic metabolites including ammonia and unconjugated bilirubin to accumulate in plasma. As the population ages alternatives to liver transplantation become increasingly important. One approach for use as a bridge to transplant or recovery is the use of bioartificial liver systems (BALS) containing primary or immortalised hepatocytes as ex-vivo replacements or supports for endogenous liver function. However, exposure to the hepatotoxic metabolites present in plasma causes the rapid failure of these cells to carry out their primary metabolic functions despite remaining viable. Hypothesizing that this loss of core hepatocyte phenotypes was caused by cell senescence we exposed HepG2 cell populations, grown in both standard two-dimensional tissue culture systems and in three dimensional cultures on novel alginate modified HEMA-MBA cryogels, to physiologically reflective concentrations of hepatotoxic metabolites and cytokines. HepG2 cells are forced into senescence by the toxic metabolites in under six hours (as measured by loss of thymidine analog incorporation or detectable Ki67 staining) which is associated with a ten to twenty-fold reduction in the capacity of the cultures to synthesise albumin or urea. This state of senescence induced by liver toxins (SILT) can be prevented by preincubation with either 2-5 µM resveratrol, its major in vivo metabolite dihydroresveratrol or a series of novel resveralogues with differential capacities to scavenge radicals and activate SIRT1 (including V29 which does not interact with the protein). SILT appears to be a previously unrecognised barrier to the development of BALS which can now be overcome using small molecules that are safe for human use at concentrations readily achievable in vivo.


Assuntos
Senescência Celular , Resveratrol , Humanos , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Células Hep G2 , Resveratrol/farmacologia , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Estilbenos/farmacologia , Fígado Artificial , Sirtuína 1/metabolismo
11.
BMC Genomics ; 25(1): 514, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789922

RESUMO

BACKGROUND: In aquaculture, sturgeons are generally maintained in the confined spaces, which not only hinders sturgeon movement, but also threatens their flesh quality that seriously concerned by aquaculture industry. As a typical antioxidant, resveratrol can improve the flesh quality of livestock and poultry. However, the mechanism of resveratrol's effect on the muscle of Siberian sturgeon is still unclear. RESULTS: In this study, the dietary resveratrol increased the myofiber diameter, the content of the amino acids, antioxidant capacity markers (CAT, LDH and SOD) levels and the expression levels of mTORC1 and MYH9 in muscle of Siberian sturgeon. Further transcriptome analysis displayed that ROS production-related pathways ("Oxidative phosphorylation" and "Chemical carcinogenes-reactive oxygen species") were enriched in KEGG analysis, and the expression levels of genes related to the production of ROS (COX4, COX6A, ATPeF1A, etc.) in mitochondria were significantly down-regulated, while the expression levels of genes related to scavenging ROS (SOD1) were up-regulated. CONCLUSIONS: In summary, this study reveals that resveratrol may promote the flesh quality of Siberian sturgeon probably by enhancing myofiber growth, nutritional value and the antioxidant capacity of muscle, which has certain reference significance for the development of a new type of feed for Siberian sturgeon.


Assuntos
Antioxidantes , Peixes , Resveratrol , Animais , Resveratrol/farmacologia , Peixes/metabolismo , Peixes/crescimento & desenvolvimento , Peixes/genética , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Nutrientes/metabolismo , Ração Animal/análise , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/citologia , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Dieta/veterinária , Perfilação da Expressão Gênica
12.
ACS Nano ; 18(21): 13635-13651, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38753978

RESUMO

As an escalating public health issue, obesity and overweight conditions are predispositions to various diseases and are exacerbated by concurrent chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals (quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy alongside systemic toxic effects. Effective therapeutic approaches that selectively target adipose tissue, thereby enhancing local energy expenditure, surmounting the limitations of prevailing antiobesity modalities are highly expected. In this context, we developed a temperature-sensitive hydrogel loaded with recombinant high-density lipoprotein (rHDL) to achieve targeted delivery of resveratrol, an adipose browning activator, to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism and demonstrates natural targeting toward scavenger receptor class B type I (SR-BI), which is highly expressed by fat cells, thereby achieving a synergistic effect for the treatment of obesity. Additionally, the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled with the regulation of their degradation and drug release rate, facilitated sustainable drug release at local adipose tissues over an extended period. Following 24 days' treatment regimen, obese mice exhibited improved metabolic status, resulting in a reduction of 68.2% of their inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel facilitated the conversion of fatty acids to phospholipids (PA, PC), expediting fat mobilization, mitigating triglyceride accumulation, and therefore facilitating adipose tissue reduction. Furthermore, rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced inflammation and fostering angiogenesis in ingWAT. Collectively, this engineered local fat reduction platform demonstrated heightened effectiveness and safety through simultaneously targeting adipocytes, promoting WAT browning, regulating lipid metabolism, and controlling inflammation, showing promise for adipose-targeted therapy.


Assuntos
Tecido Adiposo , Lipoproteínas HDL , Animais , Camundongos , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Tecido Adiposo/metabolismo , Proteínas Recombinantes , Resveratrol/farmacologia , Resveratrol/química , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Hidrogéis/química , Camundongos Endogâmicos C57BL , Humanos , Masculino , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/química , Sistemas de Liberação de Medicamentos , Receptores Depuradores Classe B/metabolismo
13.
Int J Biol Macromol ; 270(Pt 2): 132388, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754685

RESUMO

Cyclodextrin-based electrospun nanofibers are promising for encapsulating and preserving unstable compounds, but quick dissolution of certain nanofibers hinders their delivery application. In this study, hydroxypropyl-ß-cyclodextrin (HPßCD) was used as an effective carrier of resveratrol (RSV) to obtain the RSV/HPßCD inclusion complex (HPIC), which was then incorporated into pullulan nanofibers. For enhancement of RSV release toward colon target, multilayer structure with a pullulan/HPIC film sandwiched between two layers of hydrophobic Eudragit S100 (ES100) nanofibers was employed. The relationship between the superiority of the ES100-pullulan/HPIC-ES100 film and its multilayer structure was verified. The intimate interactions of hydrogen bonds between two adjacent layers enhanced thermal stability, and the hydrophobic outer layers improved water contact resistance. According to release results, multilayer films also showed excellent colon-targeted delivery property and approximately 78.58 % of RSV was observed to release in colon stage. In terms of release mechanism, complex mechanism best described RSV colonic release. Additionally, ES100-pullulan/HPIC-ES100 multilayer films performed higher encapsulation efficiency when compared to the structures without HPIC, which further increased the antioxidant activity and total release amount of RSV. These results suggest a promising strategy for designing safe colonic delivery systems based on multilayer and HPIC structures with superior preservation for RSV.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina , Colo , Glucanos , Nanofibras , Resveratrol , Nanofibras/química , Glucanos/química , Resveratrol/química , Resveratrol/farmacologia , Resveratrol/administração & dosagem , Resveratrol/farmacocinética , 2-Hidroxipropil-beta-Ciclodextrina/química , Colo/metabolismo , Colo/efeitos dos fármacos , Ácidos Polimetacrílicos/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Sistemas de Liberação de Medicamentos
14.
Int J Biol Macromol ; 270(Pt 2): 132450, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772462

RESUMO

A comparative transcriptomic and metabolomic analysis of Polygonum cuspidatum leaves treated with MeJA was carried out to investigate the regulatory mechanisms of its active compounds. A total of 692 metabolites and 77,198 unigenes were obtained, including 200 differentially accumulated metabolites and 6819 differentially expressed genes. We screened potential regulatory transcription factors involved in resveratrol and flavonoids biosynthesis, and successfully identified an MYB transcription factor, PcMYB62, which could significantly decrease the resveratrol content in P. cuspidatum leaves when over-expressed. PcMYB62 could directly bind to the MBS motifs in the promoter region of stilbene synthase (PcSTS) gene and repress its expression. Besides, PcMYB62 could also repress PcSTS expression and resveratrol biosynthesis in transgenic Arabidopsis thaliana. Our results provide abundant candidate genes for further investigation, and the new finding of the inhibitory role of PcMYB62 on the resveratrol biosynthesis could also potentially be used in metabolic engineering of resveratrol in P. cuspidatum.


Assuntos
Acetatos , Ciclopentanos , Fallopia japonica , Regulação da Expressão Gênica de Plantas , Metaboloma , Oxilipinas , Proteínas de Plantas , Resveratrol , Fatores de Transcrição , Transcriptoma , Resveratrol/metabolismo , Resveratrol/farmacologia , Fallopia japonica/metabolismo , Fallopia japonica/genética , Acetatos/farmacologia , Acetatos/metabolismo , Metaboloma/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Transcriptoma/efeitos dos fármacos , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Aciltransferases/genética , Aciltransferases/metabolismo , Perfilação da Expressão Gênica , Plantas Geneticamente Modificadas/genética , Folhas de Planta/metabolismo , Folhas de Planta/genética , Folhas de Planta/efeitos dos fármacos
15.
J Agric Food Chem ; 72(20): 11465-11479, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38739781

RESUMO

Applying plant protection products (PPP) on grapevine pruning wounds is a viticultural practice used to mitigate the spread of grapevine tuck disease, which is posing serious economic losses in the vine-wine industry. However, the impact of PPP on woody tissues remains unclear. Our study, conducted in two European vineyards, investigated the effects of Cuprocol, Tessior, Esquive, and Bentogran on stilbenes, in canes of Cabernet sauvignon and Syrah, at three phenological stages. Main stilbenes, quantified by HPLC-UV-DAD (1260 Agilent Infinity System) and identified by HPLC-ESI/MS (Thermo Scientific LCQ FLEET system), included E-resveratrol, E-ε-viniferin, E-piceatannol, and E-polydatin. Canes exhibited varying proportions of individual stilbenes, reflecting differences based on climatic conditions and phenological phases, rather than on the application of specific PPP. Vines grown in cool-climate conditions exhibited higher levels of E-resveratrol, whereas vines from the Mediterranean climate area exhibited higher levels of E-ε-viniferin. We also observed divergences in the accumulation trend of wood stilbenes throughout the season in canes collected in the two different growing areas.


Assuntos
Estilbenos , Vitis , Vitis/química , Vitis/crescimento & desenvolvimento , Estilbenos/análise , Cromatografia Líquida de Alta Pressão , Extratos Vegetais/química , Doenças das Plantas/prevenção & controle , Resveratrol/análise
16.
Physiol Res ; 73(2): 239-251, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38710061

RESUMO

Oxygen therapy provides an important treatment for preterm and low-birth-weight neonates, however, it has been shown that prolonged exposure to high levels of oxygen (hyperoxia) is one of the factors contributing to the development of bronchopulmonary dysplasia (BPD) by inducing lung injury and airway hyperreactivity. There is no effective therapy against the adverse effects of hyperoxia. Therefore, this study was undertaken to test the hypothesis that natural phytoalexin resveratrol will overcome hyperoxia-induced airway hyperreactivity, oxidative stress, and lung inflammation. Newborn rats were exposed to hyperoxia (fraction of inspired oxygen - FiO2>95 % O2) or ambient air (AA) for seven days. Resveratrol was supplemented either in vivo (30 mg·kg-1·day-1) by intraperitoneal administration or in vitro to the tracheal preparations in an organ bath (100 mikroM). Contractile and relaxant responses were studied in tracheal smooth muscle (TSM) using the in vitro organ bath system. To explain the involvement of nitric oxide in the mechanisms of the protective effect of resveratrol against hyperoxia, a nitric oxide synthase inhibitor - Nomega-nitro-L-arginine methyl ester (L-NAME), was administered in some sets of experiments. The superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and the tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels in the lungs were determined. Resveratrol significantly reduced contraction and restored the impaired relaxation of hyperoxia-exposed TSM (p<0.001). L-NAME reduced the inhibitory effect of resveratrol on TSM contractility, as well as its promotion relaxant effect (p<0.01). Resveratrol preserved the SOD and GPx activities and decreased the expression of TNF-alpha and IL-1beta in hyperoxic animals. The findings of this study demonstrate the protective effect of resveratrol against hyperoxia-induced airway hyperreactivity and lung damage and suggest that resveratrol might serve as a therapy to prevent the adverse effects of neonatal hyperoxia. Keywords: Bronchopulmonary dysplasia, Hyperoxia, Airway hyperreactivity, Resveratrol, Pro-inflammatory cytokines.


Assuntos
Animais Recém-Nascidos , Displasia Broncopulmonar , Modelos Animais de Doenças , Estresse Oxidativo , Pneumonia , Resveratrol , Animais , Resveratrol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Displasia Broncopulmonar/prevenção & controle , Displasia Broncopulmonar/metabolismo , Pneumonia/prevenção & controle , Pneumonia/metabolismo , Pneumonia/induzido quimicamente , Ratos , Hiperóxia/complicações , Hiperóxia/metabolismo , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Antioxidantes/farmacologia , Hiper-Reatividade Brônquica/prevenção & controle , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/fisiopatologia , Hiper-Reatividade Brônquica/induzido quimicamente , Ratos Sprague-Dawley , Masculino
17.
Nutrients ; 16(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38794677

RESUMO

Resveratrol and caffeic acid are some of the most consumed antioxidants during the day, so their importance as sources and their benefits need to be evaluated and updated. This survey aimed not only to analyze whether young Romanian consumers are informed about the benefits of antioxidants in general, and resveratrol and caffeic acid in particular, but also to observe the degree of nutritional education of these participants. Young consumers know the concept of antioxidants relatively well; they managed to give examples of antioxidants and indicate their effects. The majority of those chosen drink wine and coffee, but many are unaware of their health advantages and antioxidant properties. Students are less familiar with the antioxidant chemicals resveratrol and caffeic acid. It is advised to have a thorough understanding of these significant antioxidants and their nutritional content as they are present in our regular diets, and further studies on different kinds of antioxidants are required to increase the awareness of people concerning their importance in daily life.


Assuntos
Antioxidantes , Ácidos Cafeicos , Café , Conhecimentos, Atitudes e Prática em Saúde , Resveratrol , Humanos , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Resveratrol/farmacologia , Resveratrol/administração & dosagem , Ácidos Cafeicos/farmacologia , Feminino , Masculino , Adulto Jovem , Adulto , Café/química , Romênia , Adolescente , Vinho/análise , Inquéritos e Questionários , Valor Nutritivo
18.
Nutrients ; 16(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794742

RESUMO

This study aimed to investigate the effects of the Mediterranean diet (MD), combined with curcumin and resveratrol supplementation, on disease activity, serum inflammatory markers, and quality of life in patients with mild-to-moderate active ulcerative colitis (UC). This study was designed as a prospective multicenter three-arm randomized controlled trial. Participants were randomized to the MD, MD + curcumin, and MD + resveratrol groups. All participants were placed on the MD for 8 weeks. The MD + curcumin group also received 1600 mg/day of curcumin supplementation, whereas the MD + resveratrol group received 500 mg/day of resveratrol supplementation for 8 weeks. Anthropometric measurements, Truelove-Witts Index, Short Form-36, Inflammatory Bowel Disease Questionnaire, Mediterranean Diet Adherence Scale (MEDAS), and laboratory tests were performed at baseline and postintervention. Within-group comparisons showed that MD, MD + curcumin, and MD + resveratrol interventions were effective in reducing disease activity and inflammation and improving quality of life in individuals with UC (p < 0.05). Between-group comparisons revealed no significant difference in all parameters except for the pain subparameter of SF-36 and the MEDAS score (p < 0.05). The MD is an effective and safe intervention to be used in clinical practice in individuals with UC.


Assuntos
Colite Ulcerativa , Curcumina , Dieta Mediterrânea , Qualidade de Vida , Resveratrol , Humanos , Colite Ulcerativa/tratamento farmacológico , Resveratrol/administração & dosagem , Resveratrol/farmacologia , Curcumina/administração & dosagem , Feminino , Masculino , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Suplementos Nutricionais , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
19.
Mol Biol Rep ; 51(1): 692, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796562

RESUMO

BACKGROUND: Resveratrol, a potent antioxidant, is known to induce the up-regulation of the internal antioxidant system. Therefore, it holds promise as a method to mitigate cryopreservation-induced injuries in bovine oocytes and embryos. This study aimed to (i) assess the enhancement in the quality of in vitro produced bovine embryos following resveratrol supplementation and (ii) monitor changes in the expression of genes associated with oxidative stress (GPX4, SOD, CPT2, NFE2L2), mitochondrial function (ATP5ME), endoplasmic reticulum function (ATF6), and embryo quality (OCT4, DNMT1, CASP3, ELOVL5). METHODS AND RESULTS: Three groups of in vitro bovine embryos were cultured with varying concentrations of resveratrol (0.01, 0.001, and 0.0001 µM), with a fourth group serving as a control. Following the vitrification process, embryos were categorized as either good or poor quality. Blastocysts were then preserved at - 80 °C for RNA isolation, followed by qRT-PCR analysis of selected genes. The low concentrations of resveratrol (0.001 µM, P < 0.05 and 0.0001 µM, P < 0.01) significantly improved the blastocyst rate compared to the control group. Moreover, the proportion of good quality vitrified embryos increased significantly (P < 0.05) in the groups treated with 0.001 and 0.0001 µM resveratrol compared to the control group. Analysis of gene expression showed a significant increase in OCT4 and DNMT1 transcripts in both good and poor-quality embryos treated with resveratrol compared to untreated embryos. Additionally, CASP3 expression was decreased in treated good embryos compared to control embryos. Furthermore, ELOVL5 and ATF6 transcripts were down-regulated in treated good embryos compared to the control group. Regarding antioxidant-related genes, GPX4, SOD, and CPT2 transcripts increased in the treated embryos, while NFE2L2 mRNA decreased in treated good embryos compared to the control group. CONCLUSIONS: Resveratrol supplementation at low concentrations effectively mitigated oxidative stress and enhanced the cryotolerance of embryos by modulating the expression of genes involved in oxidative stress response.


Assuntos
Antioxidantes , Blastocisto , Criopreservação , Estresse Oxidativo , Resveratrol , Vitrificação , Animais , Bovinos , Resveratrol/farmacologia , Vitrificação/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Criopreservação/métodos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Blastocisto/efeitos dos fármacos , Blastocisto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fertilização in vitro/veterinária , Fertilização in vitro/métodos , Embrião de Mamíferos/efeitos dos fármacos , Embrião de Mamíferos/metabolismo , Técnicas de Cultura Embrionária/métodos , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/genética , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Feminino
20.
Sci Rep ; 14(1): 12521, 2024 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822085

RESUMO

Sirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signalling and concomitantly, activating autophagy. This study analyzes the role of TSC2 acetylation levels in its translocation to the lysosome and the mitochondrial turnover in both mouse embryonic fibroblast (MEF) and in mouse insulinoma cells (MIN6) as a model of pancreatic ß cells. Resveratrol (RESV), an activator of SIRT1 activity, promotes TSC2 deacetylation and its translocation to the lysosome, inhibiting mTORC1 activity. An improvement in mitochondrial turnover was also observed in cells treated with RESV, associated with an increase in the fissioned mitochondria, positive autophagic and mitophagic fluxes and an enhancement of mitochondrial biogenesis. This study proves that TSC2 in its deacetylated form is essential for regulating mTORC1 signalling and the maintenance of the mitochondrial quality control, which is involved in the homeostasis of pancreatic beta cells and prevents from several metabolic disorders such as Type 2 Diabetes Mellitus.


Assuntos
Lisossomos , Alvo Mecanístico do Complexo 1 de Rapamicina , Mitocôndrias , Sirtuína 1 , Proteína 2 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/genética , Animais , Acetilação , Lisossomos/metabolismo , Camundongos , Mitocôndrias/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Sirtuína 1/metabolismo , Autofagia , Transporte Proteico , Resveratrol/farmacologia , Transdução de Sinais , Fibroblastos/metabolismo , Células Secretoras de Insulina/metabolismo , Linhagem Celular Tumoral
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