RESUMEN
BACKGROUND/AIMS: One of the treatments for breast cancer is surgical resection of the tumour and prevention of recurrence with postoperative radiotherapy. Unfortunately, radiotherapy is not always effective enough due to the low sensitivity of cancer cells to ionising radiation. This study aimed to evaluate the radiosensitising properties of resveratrol, piceatannol and polydatin on breast cancer cells, which differ in the presence of hormonal receptors on their surface. METHODS: The experimental part was carried out on triple-negative breast cancer cells (HCC38) and hormone-dependent cells (MCF7). The study assessed the level of cell death, changes in the expression of genes (BAX, BCL-2) and proteins related to the apoptosis process (CASPASE 3, 8 and P53), changes in the expression of antioxidant enzymes (CATALASE, SOD, GPx1/2) and NRF-2. Additionally, the expression level of RAD51 protein and histone H2AX, which are involved in DNA repair processes, was assessed. Statistical significance was evaluated by a two-way analysis of variance (ANOVA) followed by Tukey's post hoc test (p < 0.05). RESULTS: Ionising radiation in combination with resveratrol or piceatannol activates the apoptosis process by internal and external pathways. Greater sensitivity of MCF7 cells compared to HCC38 cells to ionising radiation in combination with resveratrol is associated with a weaker antioxidant response of cells and reduced intensity of DNA damage repair. DNA repair induced by ionising radiation occurs more effectively in HCC38 cells than in MCF7 cells. CONCLUSION: Resveratrol has the highest radiosensitising potential among the tested stilbene for cells of both lines. The effectiveness of ionizing radiation in combination with resveratrol (to a lesser extent with piceatannol) is more significant in MCF7 than in HCC38 cells.
Asunto(s)
Apoptosis , Radiación Ionizante , Fármacos Sensibilizantes a Radiaciones , Resveratrol , Estilbenos , Humanos , Estilbenos/farmacología , Resveratrol/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Femenino , Fármacos Sensibilizantes a Radiaciones/farmacología , Línea Celular Tumoral , Células MCF-7 , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/tratamiento farmacológico , Histonas/metabolismo , Reparación del ADN/efectos de los fármacos , Reparación del ADN/efectos de la radiación , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Recombinasa Rad51/metabolismo , Caspasa 3/metabolismo , GlucósidosRESUMEN
Resveratrol (RSV), the primary polyphenol found in grapes, has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines, including IL-1ß, IL-6, IL-1ra and TNFα. Considering the close association between chronic inflammation and cancer development, RSV's immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation, proliferation, neovascularization, and migration. Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress. In addition to immunomodulation, RSV inhibits cancer development by expressing anti-oxidant effects, causing cell cycle arrest, stimulating the function of certain enzymes, and activating cell signaling pathways. The end outcome is one of the various forms of cell death, including apoptosis, pyroptosis, necroptosis, and more, as it has been observed in vitro. RSV has been shown to act against cancer in practically every organ, while its effects on colon cancer have been documented more frequently. It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol. The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV, with a particular emphasis on cancers of the digestive tract, as a challenge for future clinical research that may contribute to the better prognosis of cancer.
Asunto(s)
Neoplasias del Sistema Digestivo , Resveratrol , Resveratrol/farmacología , Resveratrol/uso terapéutico , Humanos , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Neoplasias del Sistema Digestivo/prevención & control , Animales , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/uso terapéutico , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéuticoRESUMEN
OBJECTIVE: Accumulating experimental evidence has shown that resveratrol supplementation is effective for treating diabetic nephropathy (DN) in animal models. In this systematic review and meta-analysis, we assessed the effects and multiple mechanisms of resveratrol in animal models of DN. METHODS: Before September 2023, preclinical literature was systematically searched and screened across PubMed, Web of Science, EMBASE, and the Cochrane Library. Forty-two studies were included, and the risk of bias tool from SYRCLE was used to assess the methodological quality. Pooled overall effect sizes of the results were generated by STATA 16.0. RESULTS: The overall results provide preliminary evidence that the consumption of resveratrol can significantly reduce the mesangial index, glomerular basement membrane thickness, glomerular hypertrophy, serum creatinine, blood urea nitrogen, 24-h urinary protein, blood glucose, kidney index, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. In contrast, the levels of albumin and high-density lipoprotein cholesterol are significantly increased. However, resveratrol did not significantly reduce creatinine clearance or glycated hemoglobin levels. Dose-response analysis revealed that resveratrol was most effective at improving kidney function and reducing DN when administered at lower doses of ≤15 mg/kg/day or higher doses of 100-200 mg/kg/day, with significant improvements in biochemical kidney injury markers and a better effect on dysglycemia. CONCLUSIONS: The benefits of resveratrol in DN are likely due to its anti-inflammatory, antioxidant, metabolic regulatory, and autophagy-promoting effects. To confirm these findings for clinical use, further large-scale, long-term, high-quality preclinical trials are warranted to accurately assess the anti-DN effects and safety of resveratrol.
Asunto(s)
Nefropatías Diabéticas , Resveratrol , Resveratrol/farmacología , Resveratrol/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Animales , Progresión de la Enfermedad , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Antioxidantes/farmacología , Antioxidantes/uso terapéuticoRESUMEN
In this study, we discovered the mechanisms underlying parecoxib and resveratrol combination's anti-cancer characteristics against human colorectal cancer DLD-1 cells. We studied its anti-proliferation and apoptosis-provoking effect by utilizing cell viability 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence microscope, gene overexpression, Western blot, and flow cytometry analyses. Parecoxib enhanced the ability of resveratrol to inhibit cell viability and increase apoptosis. Parecoxib in combination with resveratrol strongly enhanced apoptosis by inhibiting the expression of thioredoxin domain containing 5 (TXNDC5) and Akt phosphorylation. Parecoxib enhanced resveratrol-provoked c-Jun N-terminal kinase (JNK) and p38 phosphorylation. Overexpression of TXNDC5 and repression of JNK and p38 pathways significantly reversed the inhibition of cell viability and stimulation of apoptosis by the parecoxib/resveratrol combination. This study presents evidence that parecoxib enhances the anti-cancer power of resveratrol in DLD-1 colorectal cancer cells via the inhibition of TXNDC5 and Akt signaling and enhancement of JNK/p38 MAPK pathways. Parecoxib may be provided as an efficient drug to sensitize colorectal cancer by resveratrol.
Asunto(s)
Apoptosis , Supervivencia Celular , Neoplasias Colorrectales , Isoxazoles , Proteínas Proto-Oncogénicas c-akt , Resveratrol , Humanos , Resveratrol/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Isoxazoles/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fosforilación/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sinergismo Farmacológico , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Previous studies have indicated that occlusal disharmony (OD) can promote anxiety-like behaviours. However, the specific molecules involved in the development of anxiety-like behaviours and their underlying mechanisms remain unknown. METHODS: OD was produced by anterior crossbite of female mice. We measured the anxiety levels of mice in each group and screened the hippocampal mRNA expression profiles of mice in the control group and OD group. The role of target mRNA in OD-induced anxiety-like behaviours was evaluated and we preliminarily explored the possible downstream pathways. RESULTS: The results suggested that OD can induce and promote anxiety-like behaviours with/without chronic unpredictable mild stress. We found that Sirt1 was significantly downregulated within the hippocampus in OD mice. In addition, the downregulation of Sirt1 within the hippocampus in OD and control mice promoted anxiety-like behaviours, increased acetylated histone H3 expression and decreased Dnah12 transcription levels. In contrast, in OD mice subjected to an injection of resveratrol, there was a remission of anxiety-like behaviours and an upregulation of Sirt1 in the hippocampus, the effects of which were accompanied by decreased acetylated histone H3 expression and increased Dnah12 transcription levels. CONCLUSIONS: OD leads to increased sensitivity to chronic stress in mice, resulting in anxiety-like behaviours. During this process, Sirt1 acts as an effective factor in the regulation of OD-induced anxiety-like behaviours. CLINICAL RELEVANCE: OD, as a stressor, could induce anxiety-like behaviours. It investigates the impact of OD (a stressor) on the molecular genetic of the pathophysiology of major neuropsychiatric disorders.
Asunto(s)
Ansiedad , Conducta Animal , Modelos Animales de Enfermedad , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Ratones , Femenino , Maloclusión , Hipocampo/metabolismo , Resveratrol/farmacología , Regulación hacia Abajo , ARN Mensajero/metabolismoRESUMEN
Core-shell nanostructures are powerful platforms for the development of novel nanoscale drug delivery systems with sustained drug release profiles. Coaxial electrospinning is facile and convenient for creating medicated core-shell nanostructures with elaborate designs with which the sustained-release behaviors of drug molecules can be intentionally adjusted. With resveratrol (RES) as a model for a poorly water-soluble drug and cellulose acetate (CA) and PVP as polymeric carriers, a brand-new electrospun core-shell nanostructure was fabricated in this study. The guest RES and the host CA molecules were designed to have a reverse gradient distribution within the core-shell nanostructures. Scanning electron microscope and transmission electron microscope evaluations verified that these nanofibers had linear morphologies, without beads or spindles, and an obvious core-shell double-chamber structure. The X-ray diffraction patterns and Fourier transform infrared spectroscopic results indicated that the involved components were highly compatible and presented in an amorphous molecular distribution state. In vitro dissolution tests verified that the new core-shell structures were able to prevent the initial burst release, extend the continuous-release time period, and reduce the negative tailing-off release effect, thus ensuring a better sustained-release profile than the traditional blended drug-loaded nanofibers. The mechanism underlying the influence of the new core-shell structure with an RES/CA reverse gradient distribution on the behaviors of RES release is proposed. Based on this proof-of-concept demonstration, a series of advanced functional nanomaterials can be similarly developed based on the gradient distributions of functional molecules within electrospun multi-chamber nanostructures.
Asunto(s)
Celulosa , Preparaciones de Acción Retardada , Portadores de Fármacos , Liberación de Fármacos , Nanofibras , Resveratrol , Nanofibras/química , Preparaciones de Acción Retardada/química , Resveratrol/química , Resveratrol/administración & dosificación , Celulosa/química , Celulosa/análogos & derivados , Portadores de Fármacos/química , Polímeros/química , Espectroscopía Infrarroja por Transformada de Fourier , Sistemas de Liberación de Medicamentos/métodos , Difracción de Rayos XRESUMEN
Mitochondrial damage is an early and key marker of neuronal damage in prion diseases. As a process involved in mitochondrial quality control, mitochondrial biogenesis regulates mitochondrial homeostasis in neurons and promotes neuron health by increasing the number of effective mitochondria in the cytoplasm. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates neuronal mitochondrial biogenesis and quality control in neurodegenerative diseases via deacetylation of a variety of substrates. In a cellular model of prion diseases, we found that both SIRT1 protein levels and deacetylase activity decreased, and SIRT1 overexpression and activation significantly ameliorated mitochondrial morphological damage and dysfunction caused by the neurotoxic peptide PrP106-126. Moreover, we found that mitochondrial biogenesis was impaired, and SIRT1 overexpression and activation alleviated PrP106-126-induced impairment of mitochondrial biogenesis in N2a cells. Further studies in PrP106-126-treated N2a cells revealed that SIRT1 regulates mitochondrial biogenesis through the PGC-1α-TFAM pathway. Finally, we showed that resveratrol resolved PrP106-126-induced mitochondrial dysfunction and cell apoptosis by promoting mitochondrial biogenesis through activation of the SIRT1-dependent PGC-1α/TFAM signaling pathway in N2a cells. Taken together, our findings further describe SIRT1 regulation of mitochondrial biogenesis and improve our understanding of mitochondria-related pathogenesis in prion diseases. Our findings support further investigation of SIRT1 as a potential target for therapeutic intervention of prion diseases.
Asunto(s)
Mitocondrias , Biogénesis de Organelos , Fragmentos de Péptidos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Priones , Sirtuina 1 , Sirtuina 1/metabolismo , Sirtuina 1/genética , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Priones/metabolismo , Animales , Ratones , Fragmentos de Péptidos/metabolismo , Resveratrol/farmacología , Factores de Transcripción/metabolismo , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genéticaRESUMEN
The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.
Asunto(s)
Apoptosis , Supervivencia Celular , Fluorouracilo , Resveratrol , Neoplasias Gástricas , Resveratrol/farmacología , Resveratrol/uso terapéutico , Fluorouracilo/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Estilbenos/farmacología , Estilbenos/uso terapéutico , Humanos , Estrés Oxidativo/efectos de los fármacos , Antimetabolitos Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Masculino , Miocitos Cardíacos/efectos de los fármacos , Ratones , Movimiento Celular/efectos de los fármacosRESUMEN
Resveratrol, a potent anticancer bioactive compound, has been shown to trigger apoptosis in numerous cancer cells. Although Notch signaling promotes breast cancer apoptosis, it is unclear whether resveratrol induces apoptosis in MCF-7 cells via influencing the Notch pathway. This study aimed to evaluate the effect of resveratrol on modulating Notch signaling targets and provide critical information for employing resveratrol in breast cancer therapy. Thus, in this study, we have deciphered the effect of resveratrol against three potent genes (Notch1, Jagged1, and DLL4) of the notch signaling pathway. For mechanistic studies, in silico, and in vitro analysis was executed to investigate the apoptotic-inducing potential of resveratrol against three selected oncogenes involved in the progression of breast cancer. Docking analysis revealed the inhibitory potential of resveratrol against all three selected targets of the Notch pathway (Notch1: -5.0; Jagged-1: -5.9; DLL4: -5.8). In vitro, findings further displayed a significant reduction in cell viability in resveratrol-treated MCF-7 cancer cells, which were concomitantly related to the downregulation of Notch-1, Jagged-1, and DLL4. Moreover, the antiproliferative efficacy of resveratrol was correlated with apoptosis and modulation in the expression of Bax, Bcl-2, cyclin D1, CDK4, p21, and caspase-3 activation. Taken together, these experimental findings suggested that apoptotic inducing potential of resveratrol was mediated through a novel mechanism involving suppression of the Notch signaling pathway.
Asunto(s)
Apoptosis , Neoplasias de la Mama , Proteína Jagged-1 , Resveratrol , Transducción de Señal , Humanos , Resveratrol/farmacología , Apoptosis/efectos de los fármacos , Células MCF-7 , Transducción de Señal/efectos de los fármacos , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Femenino , Receptor Notch1/metabolismo , Receptor Notch1/genética , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Estilbenos/farmacología , Receptores Notch/metabolismo , Receptores Notch/genética , Simulación del Acoplamiento Molecular , Supervivencia Celular/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 3/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genéticaRESUMEN
Recent research has emphasized the development of efficient drug delivery systems to facilitate the delivery of biological compounds such as polyphenols via skin absorption. Phytozomes have been employed as carriers of plant compounds in this context Hydrogen bonding between plant polyphenols and the phospholipid phosphate group enables efficient encapsulation of potent compounds for enhanced drug delivery systems. Additionally, the strong affinity of phytosomes for the skin's phospholipids enhances skin absorption. In this study, phytosomes were initially formulated using the thin-layer hydration method After optimizing the synthetic parameters, phytosomes were loaded with Resveratrol and Quercetin for enhanced delivery and skin absorption potential to assess the characteristics of the synthesized phytosomes, tests were conducted to determine particle distribution and size, zeta potential, and examine the microstructure morphology using a scanning electron microscope (SEM). Furthermore, a siloxane gel base was formulated in this study, and the stability of the physicochemical and biological properties of the final prepared nanoformulation was investigated. The results of this study indicated that the formulated phytosomes exhibit optimal characteristics for facilitating high skin penetration of resveratrol and quercetin. A high skin absorption was observed after 60 days of synthesis. Additionally, the base of the siloxane gel can play a significant role in preventing the formation of scars by reducing the passage of water vapor.
Asunto(s)
Cicatriz , Geles , Quercetina , Resveratrol , Siloxanos , Resveratrol/química , Resveratrol/administración & dosificación , Resveratrol/farmacocinética , Geles/química , Siloxanos/química , Quercetina/química , Quercetina/administración & dosificación , Quercetina/farmacocinética , Absorción Cutánea/efectos de los fármacos , Tamaño de la Partícula , Animales , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Piel/metabolismo , Piel/efectos de los fármacos , Fitoquímicos/química , FitosomasRESUMEN
The medicinal properties of resveratrol have garnered increasing attention from researchers. Extensive data have been accumulated on its use in treating cardiovascular diseases, immune system disorders, cancer, neurological diseases, and behavioral disorders. The protective mechanisms of resveratrol, particularly in anxiety-related stress disorders, have been well documented. However, less attention has been given to the side effects of resveratrol. This review explores not only the mechanisms underlying the anxiolytic effects of resveratrol but also the mechanisms that may lead to increased anxiety following resveratrol treatment. Understanding these mechanisms is crucial for enhancing the efficacy of resveratrol in managing anxiety disorders associated with stress and PTSD.
Asunto(s)
Ansiolíticos , Trastornos de Ansiedad , Ansiedad , Resveratrol , Resveratrol/farmacología , Humanos , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Animales , Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/tratamiento farmacológico , Estrés Psicológico/tratamiento farmacológico , Trastornos por Estrés Postraumático/tratamiento farmacológicoRESUMEN
Resveratrol has been reported to promote immunity and decrease oxidative stress, but which demonstrates biphasic effects relied on the use concentration. In this study, the effects of diet supplement with a relative high concentration of resveratrol (0.32 mg/kg) on metabolism, antioxidation and apoptosis of liver were investigated in Siberian sturgeon. The results showed that resveratrol significantly increased the lipid synthesis and the apoptosis, but did not either activate the antioxidant NRF2/KEAP1 pathway or enhance the antioxidant enzyme activity. Transcriptome analysis revealed significant changes in regulatory pathways related to glycolipid, including PPAR signaling pathway, Insulin signaling pathway, Fatty acid biosynthesis, and Glycolysis/Gluconeogenesis. In addition, resveratrol significantly increased the lipid synthesis genes (accα and fas), fatty acid transport gene (fatp 6) and gluconeogenesis gene (gck), but decreased the survival-promoting genes (gadd45ß and igf 1). These findings highlight a significant effect of resveratrol on glycolipid metabolism in Siberian sturgeon. Moreover, this study also demonstrated that 0.32 mg/kg resveratrol has physiological toxicity to the liver of Siberian sturgeon, indicating that this dose is too high for Siberian sturgeon. Thus, our study provides a valuable insight for future research and application of resveratrol in fish.
Asunto(s)
Apoptosis , Peces , Perfilación de la Expresión Génica , Resveratrol , Animales , Resveratrol/farmacología , Peces/genética , Peces/metabolismo , Apoptosis/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Antioxidantes/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Lipogénesis/genéticaRESUMEN
Systemic lupus erythematosus (SLE) is a multisystem chronic autoimmune disease with a complex occurrence and development process, associated with immune disorders, uncertain prognosis, and treatment modalities which vary by patient and disease activity. At present, the clinical treatment of SLE mainly focuses on hormones and immunosuppressants. In recent years, the research on new treatment strategies for SLE has been booming, and strong preclinical results and clinical research have promoted the development of numerous drugs (such as rituximab and orencia), but numerous of these drugs have failed to achieve effectiveness in clinical trials, and there are some adverse reactions. Recent evidence suggests that resveratrol (RSV) has the effect of ameliorating immune disorders by inhibiting overactivation of immune cells. In the present review, advances in research on the protective effects and potential mechanisms of RSV against SLE are summarized and the potential potency of RSV and its use as a promising therapeutic option for the treatment of SLE are highlighted.
Asunto(s)
Lupus Eritematoso Sistémico , Resveratrol , Resveratrol/uso terapéutico , Resveratrol/farmacología , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , AnimalesRESUMEN
Resveratrol is a promising functional ingredient applied in food products. However, low bioavailability and poor water solubility, which can be improved by glycosylation, hinder its application. A uridine diphosphate-dependent glycosyltransferase (UGT) from Bacillus subtilis 168 (named UGTBS) presents potential application for resveratrol glycosylation; nonetheless, imprecise regioselectivity renders the synthesis of resveratrol-3-O-ß-D-glucoside (polydatin) difficult. Therefore, molecular evolution was applied to UGTBS. A triple mutant Y14I/I62G/M315W was developed for 3-OH glycosylation of resveratrol and polydatin accounted for 91% of the total product. Kinetic determination and molecular docking indicated that the enhancement of hydrogen bond interaction and altered conformation of the binding pocket increases the enzyme's affinity for the 3-OH group, stabilizing the enzyme-substrate intermediate and promoting polydatin formation. Furthermore, a fed-batch cascade reaction by periodic addition of resveratrol was conducted and nearly 20 mM polydatin was obtained. The mutant Y14I/I62G/M315W can be used for polydatin manufacture.
Asunto(s)
Bacillus subtilis , Glucósidos , Glicosiltransferasas , Simulación del Acoplamiento Molecular , Estilbenos , Glucósidos/química , Glucósidos/metabolismo , Estilbenos/química , Estilbenos/metabolismo , Glicosiltransferasas/genética , Glicosiltransferasas/química , Glicosiltransferasas/metabolismo , Bacillus subtilis/enzimología , Bacillus subtilis/genética , Bacillus subtilis/química , Cinética , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Glicosilación , Resveratrol/química , Resveratrol/metabolismo , Especificidad por Sustrato , Ingeniería de ProteínasRESUMEN
Resveratrol is converted to various metabolites by gut microbiota. Human and rat liver 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) are critical for glucocorticoid activation, while 11ß-HSD2 in the kidney does the opposite reaction. It is still uncertain whether resveratrol and its analogues selectively inhibit 11ß-HSD1. In this study, the inhibitory strength, mode of action, structure-activity relationship (SAR), and docking analysis of resveratrol analogues on human, rat, and mouse 11ß-HSD1 and 11ß-HSD2 were performed. The inhibitory strength of these chemicals on human 11ß-HSD1 was dihydropinosylvin (6.91 µM) > lunularin (45.44 µM) > pinostilbene (46.82 µM) > resveratrol (171.1 µM) > pinosylvin (193.8 µM) > others. The inhibitory strength of inhibiting rat 11ß-HSD1 was pinostilbene (9.67 µM) > lunularin (17.39 µM) > dihydropinosylvin (19.83 µM) > dihydroresveratrol (23.07 µM) > dihydroxystilbene (27.84 µM) > others and dihydropinosylvin (85.09 µM) and pinostilbene (>100 µM) inhibited mouse 11ß-HSD1. All chemicals did not inhibit human, rat, and mouse 11ß-HSD2. It was found that dihydropinosylvin, lunularin, and pinostilbene were competitive inhibitors of human 11ß-HSD1 and that pinostilbene, lunularin, dihydropinosylvin, dihydropinosylvin and dihydroxystilbene were mixed inhibitors of rat 11ß-HSD1. Docking analysis showed that they bind to the steroid-binding site of human and rat 11ß-HSD1. In conclusion, resveratrol and its analogues can selectively inhibit human and rat 11ß-HSD1, and mouse 11ß-HSD1 is insensitive to the inhibition of resveratrol analogues.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1 , Simulación del Acoplamiento Molecular , Resveratrol , Estilbenos , Resveratrol/análogos & derivados , Resveratrol/farmacología , Resveratrol/química , Animales , Humanos , Ratas , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Ratones , Estilbenos/química , Estilbenos/farmacología , Simulación de Dinámica Molecular , Relación Estructura-Actividad , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/antagonistas & inhibidores , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/metabolismo , Relación Estructura-Actividad Cuantitativa , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/químicaRESUMEN
Antioxidants are endogenous and exogenous substances with the ability to inhibit oxidation processes by interacting with reactive oxygen species (ROS). ROS, in turn, are small, highly reactive substances capable of oxidizing a wide range of molecules in the human body, including nucleic acids, proteins, lipids, carbohydrates, and even small inorganic compounds. The overproduction of ROS leads to oxidative stress, which constitutes a significant factor contributing to the development of disease, not only markedly diminishing the quality of life but also representing the most common cause of death in developed countries, namely, cardiovascular disease (CVD). The aim of this review is to demonstrate the effect of selected antioxidants, such as coenzyme Q10 (CoQ10), flavonoids, carotenoids, and resveratrol, as well as to introduce new antioxidant therapies utilizing miRNA and nanoparticles, in reducing the incidence and progression of CVD. In addition, new antioxidant therapies in the context of the aforementioned diseases will be considered. This review emphasizes the pleiotropic effects and benefits stemming from the presence of the mentioned substances in the organism, leading to an overall reduction in cardiovascular risk, including coronary heart disease, dyslipidaemia, hypertension, atherosclerosis, and myocardial hypertrophy.
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Antioxidantes , Enfermedades Cardiovasculares , Estrés Oxidativo , Humanos , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Resveratrol/farmacología , Resveratrol/uso terapéutico , Ubiquinona/análogos & derivados , Ubiquinona/uso terapéutico , Ubiquinona/farmacología , Carotenoides/uso terapéutico , Carotenoides/farmacología , Flavonoides/farmacología , Flavonoides/uso terapéutico , MicroARNs/metabolismoRESUMEN
Polyphenols exert beneficial effects on host metabolism, which may be mediated by the gut microbiota. We investigated sex-specific differences in microbiota composition and interactions with cardiometabolic parameters after polyphenol supplementation in individuals with overweight/obesity. In a double-blind, randomized, placebo-controlled trial, 19 women and 18 men with normal glucose tolerance and body mass index >25 kg/m2 received epigallocatechin-3-gallate and resveratrol (EGCG+RES, 282 + 80 mg/d) or placebo supplements for 12 weeks. Fecal microbiota composition (16S rRNA gene amplicon sequencing, V3-V4 region), in vivo whole-body fat oxidation (indirect calorimetry), and mitochondrial respiration in permeabilized skeletal muscle fibers (SkM-Ox; ex vivo respirometry) were determined pre- and post-intervention. Overall, EGCG+RES supplementation did not affect gut microbiota composition. Akkermansia, Ruminococcaceae UCG-002, Subdoligranulum, and Lachnospiraceae UCG-004 were more abundant, while Veillonella, Tyzzerella 4, Clostridium innocuum group, Ruminococcus gnavus group, Escherichia-Shigella, and an uncultured Ruminococcaceae family genus were less abundant in women compared to men. In women, only baseline Eubacterium ventriosum group abundance correlated with EGCG+RES-induced changes in SkM-Ox. In men, low Dorea, Barnsiella, Anaerotruncus, Ruminococcus, Subdoligranulum, Coprococcus, Eubacterium ventriosum group, Ruminococcaceae UCG-003, and a Ruminococcaceae family genus abundance, and high Blautia abundance at baseline were associated with improvements in SkM-Ox. Changes in whole-body fat oxidation were not associated with gut microbiota features. We conclude that baseline microbiota composition predicts changes in SkM-Ox as a result of EGCG+RES supplementation in men but not in women. Men may be more prone to diet-induced, gut microbiota-related improvements in cardiometabolic health. These sex-differences should be further investigated in future precision-based intervention studies.
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Catequina , Suplementos Dietéticos , Microbioma Gastrointestinal , Obesidad , Sobrepeso , Polifenoles , Resveratrol , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Femenino , Obesidad/microbiología , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Método Doble Ciego , Sobrepeso/microbiología , Sobrepeso/metabolismo , Sobrepeso/tratamiento farmacológico , Adulto , Resveratrol/farmacología , Resveratrol/administración & dosificación , Polifenoles/farmacología , Polifenoles/metabolismo , Polifenoles/administración & dosificación , Catequina/análogos & derivados , Catequina/farmacología , Catequina/metabolismo , Catequina/administración & dosificación , Persona de Mediana Edad , Heces/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Bacterias/efectos de los fármacos , Factores Sexuales , ARN Ribosómico 16S/genéticaRESUMEN
OBJECTIVE: To explore whether Resveratrol (RSV) can inhibit the spontaneous senescence of human bone marrow-derived mesenchymal stem cells (MSC). METHODS: MSC were serially cultured to passage 13 and passage 15 to establish model groups exhibiting spontaneous senescence, respectively. MSC at passage 13 and passage 15 were treated with 5 nmol/L RSV for 48 h to establish the RSV-treated groups. SA-ß-Gal staining was used to detect cell senescence. MTT assay was used to detect cell proliferation. RT-PCR method was used to detect senescenceîassociated telomerase activity. Western blot was used to detect the senescence-associated protein level of the phosphorylated-mTOR. RESULTS: SA-ß-Gal staining showed that the senescent cells of MSC in RSV-treated group was significantly less than those in the model group (RSV group compared with model group at passage 13, P < 0.05; RSV group compared with model group at passage 15, P < 0.01). The cell proliferation ability of MSC in RSV-treated group was significantly higher than those in model group, at 72 h in passage 13, there was significant difference between RSV-treated group and model group (P < 0.05). RT-PCR results showed that the hTERT mRNA expression of MSC in RSV-treated group was higher than that in model group, which was significantly different between RSV-treated group and model group at passage 13 (P < 0.05). Western blot results showed that the phosphorylated (Ser2448)-mTOR level of MSC in RSV-treated group was lower than that in model group, which was significantly different between RSV-treated group and model group at passage 13 (P < 0.05). CONCLUSION: RSV can inhibit the spontaneous senescence of human MSC by mediating mTOR activity.
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Células de la Médula Ósea , Proliferación Celular , Senescencia Celular , Células Madre Mesenquimatosas , Resveratrol , Serina-Treonina Quinasas TOR , Telomerasa , Humanos , Resveratrol/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Senescencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células de la Médula Ósea/citología , Células Cultivadas , Telomerasa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Estilbenos/farmacologíaRESUMEN
Thrombosis is the primary cause of death in patients with cancer. Resveratrol inhibits platelet activation, a crucial pathophysiological basis of thrombosis, in healthy individuals. However, its effects and mechanisms of action in patients with colon cancer remain unknown. Here, we investigated the effect of resveratrol on platelet adhesion and aggregation in patients with colon cancer. Through numerous in vitro and in vivo analyses, including flow cytometry, western blotting, ELISA, and immunofluorescence and colon cancer rat models, we demonstrated that resveratrol reduced thrombosis in patients with colon cancer by inhibiting the phosphorylation of the MAPK and activating the cyclic-GMP/vasodilator-stimulated phosphoprotein pathway. These findings demonstrate the potential of resveratrol in reducing thrombosis in patients with colon cancer and could be used to develop novel therapeutic strategies for this condition.