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1.
Sci Adv ; 9(10): eade5519, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36888720

RESUMO

Hydroxystilbenes are a class of polyphenolic compounds that behave as lignin monomers participating in radical coupling reactions during the lignification. Here, we report the synthesis and characterization of various artificial copolymers of monolignols and hydroxystilbenes, as well as low-molecular-mass compounds, to obtain the mechanistic insights into their incorporation into the lignin polymer. Integrating the hydroxystilbenes, resveratrol and piceatannol, into monolignol polymerization in vitro, using horseradish peroxidase to generate phenolic radicals, produced synthetic lignins [dehydrogenation polymers (DHPs)]. Copolymerization of hydroxystilbenes with monolignols, especially sinapyl alcohol, by in vitro peroxidases notably improved the reactivity of monolignols and resulted in substantial yields of synthetic lignin polymers. The resulting DHPs were analyzed using two-dimensional NMR and 19 synthesized model compounds to confirm the presence of hydroxystilbene structures in the lignin polymer. The cross-coupled DHPs confirmed both resveratrol and piceatannol as authentic monomers participating in the oxidative radical coupling reactions during polymerization.


Assuntos
Biomimética , Lignina , Resveratrol , Lignina/metabolismo , Polimerização , Estresse Oxidativo
2.
J Agric Food Chem ; 71(11): 4488-4497, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36912343

RESUMO

Grapevine co-products, as canes, represent a source of compounds of interest to control vineyard diseases with a sustainable approach. We chose to study an extract that we produced from grapevine trunk and roots. This extract, enriched in complex stilbenes, strongly reduced mycelial growth and spore germination of Botrytis cinerea, the fungal agent causing gray mold. The most active stilbenes were resveratrol, r-viniferin, and ε-viniferin. This grapevine extract also inhibited the production of Botrytis laccases. Conversely, Botrytis secretome metabolized resveratrol into δ-viniferin and pallidol (2 dimers); and ε-viniferin, a dimer, into hopeaphenol, r-viniferin, and r2-viniferin (3 tetramers). r-Viniferin and hopeaphenol (2 tetramers) were not metabolized. The biotransformed extract maintained an effective antimycelial activity. This study provides evidence that a grapevine extract enriched in oligomerized stilbenes exerts different anti-Botrytis activities, notwithstanding the ability of the fungus to metabolize some stilbenes.


Assuntos
Estilbenos , Vitis , Resveratrol/farmacologia , Antifúngicos , Vitis/metabolismo , Estilbenos/farmacologia , Estilbenos/metabolismo , Extratos Vegetais/farmacologia
3.
J Ocul Pharmacol Ther ; 39(2): 148-158, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36867160

RESUMO

Purpose: Proliferative vitreoretinopathy (PVR) is currently treated surgically. Reliable pharmaceutical options would be desirable, and numerous drugs have been proposed. This in vitro study is intended to systematically compare and determine the most promising candidates for the treatment of PVR. Methods: A structured literature review was conducted in the "PubMed" database to identify previously published agents proposed for medical treatment of PVR -36 substances that met the inclusion criteria. Toxicity and antiproliferative effects were evaluated on primary human retinal pigment epithelial (hRPE) using colorimetric viability assays. The seven substances with the widest therapeutic range between toxicity and no longer detectable antiproliferative effect were then validated with a bromodeoxyuridine assay and a scratch wound healing assay using primary cells derived from surgically excised human PVR membranes (hPVR). Results: Among 36 substances, 12 showed no effect on hRPE at all. Seventeen substances had a significant (P < 0.05) toxic effect of which nine did not have an antiproliferative effect. Fifteen substances significantly reduced hRPE proliferation (P < 0.05). The seven most promising drugs with the highest difference between toxicity and antiproliferative effects on hRPE were dasatinib, methotrexate, resveratrol, retinoic acid, simvastatin, tacrolimus, and tranilast. Whereof resveratrol, simvastatin, and tranilast additionally showed antiproliferative and dasatinib, resveratrol, and tranilast antimigratory effects on hPVR (P < 0.05). Conclusion: This study presents a systematic comparison of drugs that have been proposed for PVR treatment in a human disease model. Dasatinib, resveratrol, simvastatin, and tranilast seem to be promising and are well-characterized in human use.


Assuntos
Vitreorretinopatia Proliferativa , Humanos , Vitreorretinopatia Proliferativa/tratamento farmacológico , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Epitélio Pigmentado da Retina
4.
BMC Complement Med Ther ; 23(1): 81, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932392

RESUMO

BACKGROUND: Resveratrol and omega-3 have been shown to prevent atherosclerosis. However, histopathological changes and their comparison have not been studied well. This study investigated the therapeutic effects of resveratrol and omega-3 in experimental atherosclerosis of mice. METHODS: We divided sixty 6-week-old male C57BL/6 mice into six groups and followed for 10 weeks: (1) standard diet, (2) atherogenic diet, (3) atherogenic diet along with resveratrol from the start of the sixth week, (4) atherogenic diet along with omega-3 from the start of the sixth week, (5) standard diet along with resveratrol from the start of the sixth week, (6) standard diet along with omega-3 from the start of the sixth week. RESULTS: The mice fed on an atherogenic diet had a larger fat area and a thicker aortic wall thickness than mice fed on a standard diet. The use of omega-3 and resveratrol in the mice with an atherogenic diet resulted in a significantly reduced fat area (p-value = 0.003), and resveratrol had a significantly higher effect. Omega-3 or resveratrol induced a significant reduction in aortic wall thickness in mice on an atherogenic diet, and there was no significant difference between them. Among the mice with a standard diet, this study did not observe any significant changes in the fat area or the aortic wall thickness with the consumption of omega-3 or resveratrol. CONCLUSIONS: Resveratrol and omega-3 had a regressive and therapeutic role in atherosclerosis, with a more significant effect in favor of resveratrol.


Assuntos
Aterosclerose , Ácidos Graxos Ômega-3 , Camundongos , Masculino , Animais , Resveratrol/farmacologia , Camundongos Endogâmicos C57BL , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Dieta Aterogênica , Aorta/patologia , Ácidos Graxos Ômega-3/farmacologia
5.
Biomed Environ Sci ; 36(2): 135-145, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36861192

RESUMO

Objective: This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism. Methods: The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model. Results: RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice. Conclusion: Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.


Assuntos
Sepse , Vibrio vulnificus , Animais , Camundongos , Necroptose , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Sepse/tratamento farmacológico , Western Blotting
6.
Food Res Int ; 165: 112376, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36869462

RESUMO

Untargeted metabolomics with the combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) was applied to investigate the impact of resveratrol and pterostilbene supplementation on the metabolic fingerprint of the Wistar rats liver with induced liver steatosis. RP-LC and HILIC in both ionisation modes were employed to analyse the liver samples (n = 40) from Wistar rats fed with a high-fat and high-fructose diet, supplemented or not with resveratrol and pterostilbene. After univariate and multivariate statistical analysis, 34 metabolites were highlighted in the different diets and elucidated. Despite the structural similarity, different alterations in liver metabolism were observed by the supplementations. Resveratrol treatment was characterised by the alteration in metabolism of 17 lysophospholipids, while pterostilbene affected some vitamins and derivatives, among others. IMS has demonstrated great potential in the elucidation process thanks to the additional structural descriptor the CCS (Å2), providing more confidence in the identification.


Assuntos
Fígado Gorduroso , Ratos , Animais , Resveratrol , Ratos Wistar , Biomarcadores , Modelos Animais
7.
Biomed Res Int ; 2023: 1176232, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36865484

RESUMO

Bupivacaine (BUP) may cause neurotoxic effects after spinal anesthesia. Resveratrol (RSV), a natural agonist of Silent information regulator 1 (SIRT1), protects various tissues and organs from damage by regulating endoplasmic reticulum (ER) stress. The aim of this study is to explore whether RSV could alleviate the neurotoxicity induced by bupivacaine via regulating ER stress. We established a model of bupivacaine-induced spinal neurotoxicity in rats using intrathecal injection of 5% bupivacaine. The protective effect of RSV was evaluated by injecting intrathecally with 30 µg/µL RSV in total of 10 µL per day for 4 consecutive days. On day 3 after bupivacaine administration, tail-flick latency (TFL) tests and the Basso, Beattie, and Bresnahan (BBB) locomotor scores were assessed to neurological function, and the lumbar enlargement of the spinal cord was obtained. H&E and Nissl staining were used to evaluate the histomorphological changes and the number of survival neurons. TUNEL staining was conducted to determine apoptotic cells. The expression of proteins was detected by IHC, immunofluorescence, and western blot. The mRNA level of SIRT1 was determined by RT-PCR. Bupivacaine caused spinal cord neurotoxicity by inducing cell apoptosis and triggering ER stress. RSV treatment promoted the recovery of neurological dysfunction after bupivacaine administration by suppressing neuronal apoptosis and ER stress. Furthermore, RSV upregulated SIRT1 expression and inhibited PERK signaling pathway activation. In summary, resveratrol suppresses bupivacaine-induced spinal neurotoxicity in rats by inhibiting endoplasmic reticulum stress via SIRT1 modulation.


Assuntos
Síndromes Neurotóxicas , Sirtuína 1 , Animais , Ratos , Resveratrol/farmacologia , Medula Espinal , Bupivacaína/toxicidade , Estresse do Retículo Endoplasmático
8.
Nutrients ; 15(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36904236

RESUMO

Bone healing is a major clinical issue, especially in bone defects of critical dimensions. Some studies have reported in vivo positive effects on bone healing by some bioactive compounds, such as the phenolic derivatives found in vegetables and plants, such as resveratrol, curcumin, and apigenin. The aim of this work was (1) to analyze in vitro in human dental pulp stem cells the effects of these three natural compounds on the gene expression of related genes downstream to RUNX2 and SMAD5, key factor transcriptions associated with osteoblast differentiation, in order to better understand the positive effects that can occur in vivo in bone healing, and (2) to evaluate in vivo the effects on bone healing of critical-size defects in the calvaria in rats of these three nutraceuticals tested in parallel and for the first time administered by the gastric route. Upregulation of the RUNX2, SMAD5, COLL1, COLL4, and COLL5 genes in the presence of apigenin, curcumin, and resveratrol was detected. In vivo, apigenin induced more consistent significant bone healing in critical-size defects in rat calvaria compared to the other study groups. The study findings encourage a possible therapeutic supplementation with nutraceuticals during the bone regeneration process.


Assuntos
Curcumina , Ratos , Humanos , Animais , Resveratrol , Curcumina/farmacologia , Apigenina , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Osteogênese , Suplementos Nutricionais , Adjuvantes Imunológicos
9.
Nutrients ; 15(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36904255

RESUMO

Global epidemiologic evidence supports an interrelationship between sleep disorders and fruits and vegetable ingestion. Polyphenols, a broad group of plant substances, are associated with several biologic processes, including oxidative stress and signaling pathways that regulate the expression of genes promoting an anti-inflammatory environment. Understanding whether and how polyphenol intake is related to sleep may provide avenues to improve sleep and contribute to delaying or preventing the development of chronic disease. This review aims to assess the public health implications of the association between polyphenol intake and sleep and to inform future research. The effects of polyphenol intake, including chlorogenic acid, resveratrol, rosmarinic acid, and catechins, on sleep quality and quantity are discussed to identify polyphenol molecules that may improve sleep. Although some animal studies have investigated the mechanisms underlying the effects of polyphenols on sleep, the paucity of trials, especially randomized controlled trials, does not allow for conducting a meta-analysis to reach clear conclusions about the relationships among these studies to support the sleep-improving effects of polyphenols.


Assuntos
Polifenóis , Sono , Animais , Humanos , Polifenóis/farmacologia , Resveratrol , Frutas/química , Verduras
10.
Microb Cell Fact ; 22(1): 46, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36890537

RESUMO

BACKGROUND: Resveratrol is a commercially available stilbenoid widely used as dietary supplements, functional food ingredients, and cosmetic ingredients due to its diverse physiological activities. The production of resveratrol in microorganisms provides an ideal source that reduces the cost of resveratrol, but the titer in Saccharomyces cerevisiae was still much lower than that in other hosts. RESULTS: To achieve enhanced production of resveratrol in S. cerevisiae, we constructed a biosynthetic pathway via combining phenylalanine and tyrosine pathways by introducing a bi-functional phenylalanine/tyrosine ammonia lyase from Rhodotorula toruloides. The combination of phenylalanine pathway with tyrosine pathway led to a 462% improvement of resveratrol production in yeast extract peptone dextrose (YPD) medium with 4% glucose, suggesting an alternative strategy for producing p-coumaric acid-derived compounds. Then the strains were further modified by integrating multi-copy biosynthetic pathway genes, improving metabolic flux to aromatic amino acids and malonyl-CoA, and deleting by-pathway genes, which resulted in 1155.0 mg/L resveratrol in shake flasks when cultured in YPD medium. Finally, a non-auxotrophic strain was tailored for resveratrol production in minimal medium without exogenous amino acid addition, and the highest resveratrol titer (4.1 g/L) ever reported was achieved in S. cerevisiae to our knowledge. CONCLUSIONS: This study demonstrates the advantage of employing a bi-functional phenylalanine/tyrosine ammonia lyase in the biosynthetic pathway of resveratrol, suggesting an effective alternative in the production of p-coumaric acid-derived compounds. Moreover, the enhanced production of resveratrol in S. cerevisiae lays a foundation for constructing cell factories for various stilbenoids.


Assuntos
Saccharomyces cerevisiae , Tirosina , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Resveratrol/metabolismo , Tirosina/metabolismo , Fenilalanina/metabolismo , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo , Engenharia Metabólica/métodos
11.
Vopr Pitan ; 92(1): 92-107, 2023.
Artigo em Russo | MEDLINE | ID: mdl-36883544

RESUMO

Polyphenols are diverse and widespread bioactive plant-based compounds. These compounds are found in various foods such as berries, fruits, vegetables, cereals, nuts, coffee, cacao, spices, seeds. They are divided into phenolic acids, stilbenes, flavonoids, lignans depending on their molecular structure. They attract the attention of researchers due to wide range of biological effects on human body. The purpose of this work was to analyze modern scientific publications on the biological effects of polyphenols. Material and methods. The review is based on publications presented in the PubMed, Google Scholar, ResearchGate, Elsevier, eLIBRARY, Cyberleninka databases using "polyphenols", "flavonoids", "resveratrol", "quercetin", "catechins" as key words. Preference was given to original researches over the past 10 years published in refereed journals. Results. Oxidative stress, chronic inflammation, microbiome disorders, insulin resistance, excessive protein glycation, and genotoxic effects are at the heart of the pathogenesis of many diseases, including those associated with age. A large amount of material has been accumulated on the antioxidant, anticarcinogenic, epigenetic, metabolic, geroprotective, anti-inflammatory and antiviral effects of polyphenols. This gives reasons to consider polyphenols as very promising micronutrients, which inclusion in the diet can reduce the risk of developing cardiovascular, oncological, neurodegenerative diseases, diabetes mellitus, obesity, metabolic syndrome, premature aging, that is, the main causes of death, a decrease in the duration and quality of life of a modern person. Conclusion. Expanding the range of products enriched with polyphenols with their high bioavailability is a promising area of scientific research and development of production in order to prevent socially significant age-associated diseases.


Assuntos
Polifenóis , Qualidade de Vida , Humanos , Polifenóis/farmacologia , Flavonoides , Resveratrol , Frutas
12.
Cells ; 12(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36899817

RESUMO

Resveratrol is a polyphenol that acts as antioxidants do, protecting the body against diseases, such as diabetes, cancer, heart disease, and neurodegenerative disorders, such as Alzheimer's (AD) and Parkinson's diseases (PD). In the present study, we report that the treatment of activated microglia with resveratrol after prolonged exposure to lipopolysaccharide is not only able to modulate pro-inflammatory responses, but it also up-regulates the expression of decoy receptors, IL-1R2 and ACKR2 (atypical chemokine receptors), also known as negative regulatory receptors, which are able to reduce the functional responses promoting the resolution of inflammation. This result might constitute a hitherto unknown anti-inflammatory mechanism exerted by resveratrol on activated microglia.


Assuntos
Lipopolissacarídeos , Microglia , Resveratrol/metabolismo , Lipopolissacarídeos/metabolismo , Microglia/metabolismo , Citocinas/metabolismo , Anti-Inflamatórios/metabolismo
13.
Int J Mol Sci ; 24(5)2023 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-36901993

RESUMO

Bladder cancer is the most common tumor of the urinary system, with a high incidence in the male population. Surgery and intravesical instillations can eradicate it, although recurrences are very common, with possible progression. For this reason, adjuvant therapy should be considered in all patients. Resveratrol displays a biphasic dose response both in vitro and in vivo (intravesical application) with an antiproliferative effect at high concentrations and antiangiogenic action in vivo (intraperitoneal application) at a low concentration, suggesting a potential role for it in clinical management as an adjuvant to conventional therapy. In this review, we examine the standard therapeutical approach to bladder cancer and the preclinical studies that have investigated resveratrol in xenotransplantation models of bladder cancer. Molecular signals are also discussed, with a particular focus on the STAT3 pathway and angiogenic growth factor modulation.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Masculino , Resveratrol/uso terapêutico , Neoplasias da Bexiga Urinária/patologia , Administração Intravesical , Terapia Combinada
14.
Int J Mol Sci ; 24(5)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36902421

RESUMO

Frequent development of resistance to chemotherapeutic agents such as 5-flourouracil (5-FU) complicates the treatment of advanced colorectal cancer (CRC). Resveratrol is able to utilize ß1-integrin receptors, strongly expressed in CRC cells, to transmit and exert anti-carcinogenic signals, but whether it can also utilize these receptors to overcome 5-FU chemoresistance in CRC cells has not yet been investigated. Effects of ß1-integrin knockdown on anti-cancer capabilities of resveratrol and 5-FU were investigated in HCT-116 and 5-FU-resistant HCT-116R CRC tumor microenvironment (TME) with 3D-alginate as well as monolayer cultures. Resveratrol increased CRC cell sensitivity to 5-FU by reducing TME-promoted vitality, proliferation, colony formation, invasion tendency and mesenchymal phenotype including pro-migration pseudopodia. Furthermore, resveratrol impaired CRC cells in favor of more effective utilization of 5-FU by down-regulating TME-induced inflammation (NF-kB), vascularisation (VEGF, HIF-1α) and cancer stem cell production (CD44, CD133, ALDH1), while up-regulating apoptosis (caspase-3) that was previously inhibited by TME. These anti-cancer mechanisms of resveratrol were largely abolished by antisense oligonucleotides against ß1-integrin (ß1-ASO) in both CRC cell lines, indicating the particular importance of ß1-integrin receptors for the 5-FU-chemosensitising effect of resveratrol. Lastly, co-immunoprecipitation tests showed that resveratrol targets and modulates the TME-associated ß1-integrin/HIF-1α signaling axis in CRC cells. Our results suggest for the first time the utility of the ß1-integrin/HIF-1α signaling axis related to chemosensitization and overcoming chemoresistance to 5-FU in CRC cells by resveratrol, underlining its potential supportive applications in CRC treatment.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Humanos , Resveratrol/farmacologia , Integrina beta1/metabolismo , Neoplasias Colorretais/patologia , Fluoruracila/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos
15.
Molecules ; 28(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36903296

RESUMO

Acute altitude hypoxia represents the cause of multiple adverse consequences. Current treatments are limited by side effects. Recent studies have shown the protective effects of resveratrol (RSV), but the mechanism remains unknown. To address this, the effects of RSV on the structure and function of hemoglobin of adult (HbA) were preliminarily analyzed using surface plasmon resonance (SPR) and oxygen dissociation assays (ODA). Molecular docking was conducted to specifically analyze the binding regions between RSV and HbA. The thermal stability was characterized to further validate the authenticity and effect of binding. Changes in the oxygen supply efficiency of HbA and rat RBCs incubated with RSV were detected ex vivo. The effect of RSV on the anti-hypoxic capacity under acute hypoxic conditions in vivo was evaluated. We found that RSV binds to the heme region of HbA following a concentration gradient and affects the structural stability and rate of oxygen release of HbA. RSV enhances the oxygen supply efficiency of HbA and rat RBCs ex vivo. RSV prolongs the tolerance times of mice suffering from acute asphyxia. By enhancing the oxygen supply efficiency, it alleviates the detrimental effects of acute severe hypoxia. In conclusion, RSV binds to HbA and regulates its conformation, which enhances oxygen supply efficiency and improves adaption to acute severe hypoxia.


Assuntos
Hemoglobinas , Hipóxia , Animais , Camundongos , Ratos , Resveratrol , Simulação de Acoplamento Molecular , Hemoglobinas/química , Oxigênio/química
16.
Saudi Med J ; 44(3): 246-252, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36940961

RESUMO

OBJECTIVES: To evaluate the anti-cancer effect of resveratrol on Michigan cancer foundation-7 (MCF-7) and hepatoblastoma cell line (HepG2) cells. METHODS: The study was carried out at the Department of Botany and Microbiology, Prince Sattam bin Abdulaziz University, Al-kharj, Saudi Arabia, from August 2022 to October 2022. Different concentrations of resveratrol were added to the MCF-7 and HepG2 cell lines. Cell death and proliferation were measured with MTT and Trypan blue exclusion assays. Apoptosis markers were assessed by using a quantitative PCR assay (qPCR). RESULTS: The resveratrol was shown to suppress the proliferation of MCF-7 and HepG2 cells at dose- and time-dependent. The cytotoxic effect of resveratrol was observed even at 100 µM after 24 hours. In comparison to untreated cells, resveratrol treatment reduced the viability of MCF-7 cells to roughly 57.5% with a half maximal inhibitory concentration (IC50) of 51.18 µM and HepG2 cells to 56.2% with an IC50 of 57.4 µM. Furthermore, in the tested cell lines, resveratrol was able to induce apoptosis mediated by elevated apoptosis markers. CONCLUSION: Resveratrol appears to be an excellent candidate agent in anticancer therapy in various human cancers.


Assuntos
Neoplasias da Mama , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Feminino , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Resveratrol/farmacologia , Linhagem Celular , Apoptose , Proliferação de Células
17.
Carbohydr Polym ; 310: 120714, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36925241

RESUMO

The pathology of Alzheimer's disease (AD) is highly correlated with obesity-induced insulin resistance. Resveratrol (Res) is a natural phenol that demonstrates a neuroprotective effect, but the bioactivity of Res is low in vivo. Here, chitosan (CS) was cross-linked with sodium tripolyphosphate (TPP) to encapsulate low water solubility Res. Next, a brain-targeted peptide (TG: TGNYKALHPHNG) was modified on the surface of Res-loaded CS/TPP nanoparticles (TG-Res-CS/TPP-NPs) to specifically deliver Res to the brain. Morris water maze results indicated that cognitive impairments were ameliorated by TG-Res-CS/TPP-NPs in obesity-related AD mice. Obesity-related insulin resistance promotes Tau phosphorylation and Aß aggregation in the brain. Administration of TG-Res-CS/TPP-NPs alleviated lipid deposition-induced insulin resistance and decreased the level of phosphorylated Tau and Aß aggregation via the JNK/AKT/GSK3ß pathway. Additionally, TG-Res-CS/TPP-NPs transported across blood-brain barrier which in turn increased glucose transporter expression levels, antioxidant enzyme activity and inhibited microglial cell activation. Thus, TG-Res-CS/TPP-NPs were more effective than Res-CS/TPP-NPs at regulating glucose homeostasis, oxidative stress and neuroinflammation in the brain. Moreover, inflammatory, lipid metabolism and oxidative stress-related gut microbiota including Helicobacter, Colidextribacter, Anaerotruncus, Parasutterella, Allobaculum, Alloprevotella, Alistipes, Bifidobacterium and Candidatus_Saccharimonas were also regulated by TG-Res-CS/TPP-NPs. This work indicates the potential use of TG-Res-CS/TPP-NPs for the delivery of Res.


Assuntos
Doença de Alzheimer , Quitosana , Microbioma Gastrointestinal , Resistência à Insulina , Nanopartículas , Camundongos , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologia , Barreira Hematoencefálica , Peptídeos
18.
Acta Biochim Pol ; 70(1): 131-135, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36735622

RESUMO

OBJECTIVE:  To investigate the effects of resveratrol on multiple organ injury and energy metabolism and its possible mechanism in preeclampsia model. METHODS:  A total of 45 clean-grade female adults Sprague Dawley (SD) rats (weight 270-320 g) were randomly divided into three groups: a control group, preeclampsia group (PE), and Preeclampsia with resveratrol treatment group (RE). Preeclampsia was induced in rats by administering 200 mg/kg/day L-NAME. Expression levels of TNF-α and IL-6 in the lungs and kidney tissues were analysed by ELISA, while the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) was determined by biochemical assays. The levels of lactic acid and pyruvate were detected using biochemical assays, while the epinephrine level in the kidney and heart tissues was determined by the ELISA method. Reverse transcription polymerase chain reaction and the western blotting were used to detect the expression of pyruvate dehydrogenase kinase 4 (PDK4) in the myocardial tissues. RESULTS:  We found that resveratrol treatment inhibited the levels of IL-6, TNF-α, and MDA in the lungs and kidney tissues, while the SOD activity was increased. Treatment with resveratrol reduced the levels of lactic acid, pyruvate, and epinephrine in the kidney and heart tissues. Furthermore, resveratrol treatment significantly increases the expression of PDK4 myocardial tissues in RE group compared to PE group. CONCLUSION:  Resveratrol may inhibit the release of tissue inflammatory factors, regulate the body's energy metabolism, and ultimately protect tissue damage caused during Preeclampsia.


Assuntos
Pré-Eclâmpsia , Humanos , Ratos , Feminino , Animais , Resveratrol , Ratos Sprague-Dawley , Pré-Eclâmpsia/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Superóxido Dismutase/metabolismo , Epinefrina , Piruvatos
19.
Gynecol Endocrinol ; 39(1): 2181652, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36824010

RESUMO

AIM: Among the natural polyphenolic compounds, resveratrol (RES) is known for reducing the effects of declining reproductive power through resisting senility, anti-oxidant and anti-inflammatory, while the molecular mechanism of RES in human ovaries is unclear. We aimed to evaluate the most likely mechanisms of RES against apoptosis induced by H2O2 in human ovary granulosa cells. METHODS: Ovarian granulosa cells from infertile women (≤35 years old) were collected. Those patients defined as polycystic ovary syndrome (PCOS), poor ovarian responder (POR) and Endometriosis were excluded. Then they were randomly divided into control group, model group and the treatment group. Cellular apoptosis was analyzed by flow cytometer method. The related protein and mRNA expressions were detected by western blot and RT-PCR. RESULTS: Apoptosis rates of the treatment group containing RES with concentrations of 1 µM and 10 µM were significantly decreased (p < 0.001). Western blot results demonstrated that the proteins levels of transforming growth factor-ß (TGF-ß), Bax and Caspase 9 were decreased, and Bcl-2 was increased under RES treatment, while the protein levels of Caspase 8, Caspase 3, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) expressed no significant difference. The results by RT-PCR of follicle and ovarian development related mRNA factors were consistent with that of western blot assay. CONCLUSION: In conclusion, the present study provides the evidence that RES may affects apoptotic factors to protect human ovarian state.


Assuntos
Infertilidade Feminina , Síndrome do Ovário Policístico , Feminino , Humanos , Adulto , Ovário/metabolismo , Resveratrol/farmacologia , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Células da Granulosa/metabolismo , Síndrome do Ovário Policístico/metabolismo , Apoptose , RNA Mensageiro/metabolismo
20.
Colloids Surf B Biointerfaces ; 224: 113205, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36801525

RESUMO

This study examined the influence of the nanoliposomes (LPs) particle size on the solubility, antioxidant stability, in vitro release profile, Caco-2 cellular transport activity, cellular antioxidant activity, and in vivo oral bioavailability of resveratrol (RSV). LPs with sizes of 300, 150, and 75 nm were prepared using the thin-lipid film hydration method, followed by ultrasonication for 0, 2, and 10 min, respectively. Formulating small LPs (< 100 nm) was effective to enhance the solubility, in vitro release profile, cellular permeability, and cellular antioxidant activity of RSV. A similar pattern was observed for in vivo oral bioavailability. However, the size reduction of RSV-loaded LPs did not promote the antioxidant stability of RSV, owing to their large surface area used to interact with harsh environments. This study provides the better understanding of the appropriate particle size range of LPs to improve their in vitro and in vivo performances of RSV as an effective carrier for oral administration.


Assuntos
Antioxidantes , Lipopolissacarídeos , Humanos , Resveratrol , Antioxidantes/farmacologia , Solubilidade , Células CACO-2 , Disponibilidade Biológica , Lipopolissacarídeos/farmacologia , Permeabilidade , Tamanho da Partícula , Administração Oral
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