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1.
Braz. j. biol ; 83: e248024, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1355855

RESUMO

Abstract By applying the in-silico method, resveratrol was docked on those proteins which are responsible for bone loss. The Molecular docking data between the resveratrol and Receptor activator of nuclear factor-kappa-Β ligand [RANKL] receptors proved that resveratrol binds tightly to the receptors, showed the highest binding affinities of −6.9, −7.6, −7.1, −6.9, −6.7, and −7.1 kcal/mol. According to in-vitro data, Resveratrol reduced the osteoclasts after treating Marrow-Derived Macrophages [BMM] with Macrophage colony-stimulating factor [MCSF] 20ng / ml and RANKL 50ng / ml, with different concentrations of resveratrol (2.5, 10 μg / ml) For 7 days, the cells were treated with MCSF (20 ng / ml) and RANKL (40 ng / ml) together with concentrated trimethyl ether and resveratrol (2.5, 10 μg / ml) within 12 hours. Which, not affect cell survival. After fixing osteoclast cells with formaldehyde fixative on glass coverslip followed by incubation with 0.1% Triton X-100 in PBS for 5 min and after that stain with rhodamine phalloidin staining for actin and Hoechst for nuclei. Fluorescence microscopy was performed to see the distribution of filaments actin [F.actin]. Finally, resveratrol reduced the actin ring formation. Resveratrol is the best bioactive compound for drug preparation against bone loss.


Resumo Com a aplicação do método in-silico, o resveratrol foi ancorado nas proteínas responsáveis ​​pela perda óssea. Os dados de docking molecular entre o resveratrol e o ligante do receptor ativador do fator nuclear kappa-Β [Receptor Activator of Nuclear Factor kappa-B Ligant (RANKL)] provaram que o resveratrol se liga fortemente aos receptores, mostraram as afinidades de ligação mais altas de −6,9, −7,6, −7,1, −6,9, - 6,7 e -7,1 kcal / mol. De acordo com dados in-vitro, o resveratrol reduziu os osteoclastos após o tratamento de macrófagos derivados da medula óssea [Bone Marrow-derived Macrophage (BMM)] com fator estimulador de colônias de macrófagos [Macrophage Colony-Stimulating Factor (MCSF)] 20ng / ml e RANKL 50ng / ml, com diferentes concentrações de resveratrol (2,5, 10 μg / ml). Durante sete dias, as células foram tratadas com MCSF (20 ng / ml) e RANKL (40 ng / ml) juntamente com éter trimetílico concentrado e resveratrol (2,5, 10 μg / ml) em 12 horas, processo que não afeta a sobrevivência celular. Após a fixação de células de osteoclastos com fixador de formaldeído em lamela de vidro seguido de incubação com 0,1% Triton X-100 em PBS por 5 min, foi realizado posteriormente o procedimento para corar com rodamina faloidina a actina e Hoechst os núcleos. A microscopia de fluorescência foi realizada para ver a distribuição dos filamentos de actina [F.actina]. Finalmente, o resveratrol reduziu a formação do anel de actina. O resveratrol é o melhor composto bioativo para o preparo de medicamentos contra a perda óssea.


Assuntos
Osteoclastos , Ligante RANK , Diferenciação Celular , Simulação de Acoplamento Molecular , Resveratrol/farmacologia
2.
Int J Mol Med ; 49(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35137921

RESUMO

The aim of the present study was to elucidate the effect of resveratrol on non­alcoholic steatohepatitis (NASH), and the molecular basis in mice and Hepa1­6 cells, in order to verify its therapeutic effect. C57BL/6J mice were fed a methionine­choline­deficient (MCD) diet to induce steatohepatitis and were treated with resveratrol. Mouse sera were collected for biochemical analysis and enzyme­linked immunosorbent assay, and livers were obtained for histological observation, and mmu­microRNA (miR)­599 and inflammation­related gene expression analysis. Hepa1­6 cells were treated with palmitic acid to establish a NASH cell model, and were then treated with resveratrol, or transfected with mmu­miR­599 mimic, mmu­miR­599 inhibitor or recombinant pregnane X receptor (PXR) plasmid. Subsequently, the cells were collected for mmu­miR­599 and inflammation­related gene expression analysis. Reverse transcription­quantitative polymerase chain reaction and western blotting were used to assess mmu­miR­599 expression levels, and the mRNA and protein expression levels of PXR and inflammation­related genes. The binding site of mmu­miR­599 in the PXR mRNA was verified by the luciferase activity assay. Mice fed an MCD diet for 4 weeks exhibited steatosis, focal necrosis and inflammatory infiltration in the liver. Resveratrol significantly reduced serum aminotransferase and malondialdehyde levels, and ameliorated hepatic injury. These effects were associated with reduced mmu­miR­599 expression, enhanced PXR expression, and downregulated levels of nuclear factor­κB, tumour necrosis factor­α, interleukin (IL)­1ß, IL­6, NOD­like receptor family pyrin domain­containing protein 3 and signal transducer and activator of transcription 3. Administration of the mmu­miR­599 mimic inhibited PXR expression in Hepa1­6 cells, whereas the mmu­miR­599 inhibitor exerted the opposite effect. A binding site for mmu­miR­599 was identified in the PXR mRNA sequence. Furthermore, overexpression of PXR inhibited the expression of inflammatory factors in Hepa1­6 cells. The present study provided evidence for the protective role of resveratrol in ameliorating steatohepatitis through regulating the mmu­miR­599/PXR pathway and the consequent suppression of related inflammatory factors. Resveratrol may serve as a potential candidate for steatohepatitis management.


Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptor de Pregnano X/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico
3.
Oxid Med Cell Longev ; 2022: 9233650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602098

RESUMO

Nonalcoholic fatty liver disease (NAFLD) defines fat accumulation in the liver, and it is commonly associated with metabolic syndromes like diabetes and obesity. Progressive NAFLD leads to nonalcoholic steatohepatitis (NASH) and ultimately causes cirrhosis and hepatocellular carcinoma, and NASH is currently a frequent cause of liver transplantation. Oxidative stress is often contributed to the progression of NAFLD, and hence, antioxidants such as silymarin, silybin, or silibinin, pentoxifylline, resveratrol, and vitamins A, C, and E are used in clinical trials against NAFLD. Silymarin induces the peroxisome proliferator-activated receptor α (PPARα), a fatty acid sensor, which promotes the transcription of genes that are required for the enzymes involved in lipid oxidation in hepatocytes. Silybin inhibits sterol regulatory element-binding protein 1 and carbohydrate response element-binding protein to downregulate the expression of genes responsible for de novo lipogenesis by activating AMP-activated protein kinase phosphorylation. Pentoxifylline inhibits TNF-α expression and endoplasmic reticulum stress-mediated inflammatory nuclear factor kappa B (NF-κB) activation. Thus, it prevents NAFLD to NASH progression. Resveratrol inhibits methylation at Nrf-2 promoters and NF-κB activity via SIRT1 activation in NAFLD conditions. However, clinically, resveratrol has not shown promising beneficial effects. Vitamin C is beneficial in NAFLD patients. Vitamin E is not effectively regressing hepatic fibrosis. Hence, its combination with antifibrotic agents is used as an adjuvant to produce a synergistic antifibrotic effect. However, to date, none of these antioxidants have been used as a definite therapeutic agent in NAFLD patients. Further, these antioxidants should be studied in NAFLD patients with larger populations and multiple endpoints in the future.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Pentoxifilina , Silimarina , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/patologia , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Pentoxifilina/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Silibina/uso terapêutico
4.
Mol Med ; 28(1): 52, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508992

RESUMO

BACKGROUND: The altered gut microbiota is implicated in the pathogenesis of liver fibrosis. Resveratrol is a candidate for the treatment of liver fibrosis, which could ameliorate the dysregulation of gut microbiota in mice. This study aimed to clarify the role and mechanism of resveratrol in gut microbiota during liver fibrosis. METHODS: A mouse model of liver fibrosis induced by CCl4 was conducted to assess the effect of resveratrol on liver fibrosis. The changes of gut microbiota in liver fibrotic mice after resveratrol intervention were assessed using 16S ribosomal RNA sequencing. The mechanism of the gut microbiota dysregulation in liver fibrosis was investigated by Sirius red staining, immunohistochemical assay, bacterial translocation (BT), EUB338 fluorescence in situ hybridization, immunofluorescence, trans-epithelial electrical resistance analysis and paracellular permeability analysis. RESULTS: Resveratrol relieved CCl4-induced liver fibrosis. Besides, resveratrol restrained the gut microbiota Staphylococcus_lentus and Staphylococcus_xylosus in the liver fibrotic mice, and the Staphylococcus_xylosus and Staphylococcus_lentus facilitated the occurrence of BT and the cultures of them enhanced the permeability of intestine. The in vivo assay corroborated that the excessive Staphylococcus_xylosus and Staphylococcus_lentus canceled the protecting effect of resveratrol on liver fibrosis, and Staphylococcus_xylosus or Staphylococcus_lentus alone had a limited impact on the liver injury of normal mice. CONCLUSION: Resveratrol ameliorated liver fibrosis by restraining the growth of Staphylococcus_xylosus and Staphylococcus_lentus.


Assuntos
Cirrose Hepática , Staphylococcus , Animais , Hibridização in Situ Fluorescente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Camundongos , Camundongos Endogâmicos BALB C , Resveratrol/farmacologia
5.
ACS Chem Neurosci ; 13(8): 1342-1354, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35385256

RESUMO

Epilepsy is a relatively complicated neurological disorder that results in seizures. The use of resveratrol in treating seizures has been reported in recent studies. However, the low bioavailability of resveratrol and the difficulty of reaching the targeted location in the brain reduce its efficacy considerably. The side effects due to the higher concentration of drugs are another matter of concern. The purpose of the present study is to enhance the antiepileptic potential of resveratrol by delivering it to the brain's targeted location by encapsulating it in glutathione-coated collagen nanoparticles. The collagen nanoparticles increase the bioavailability of resveratrol, while the transport of resveratrol to its target location in the brain is facilitated by glutathione. By encapsulating resveratrol in glutathione-coated collagen nanoparticles, the concentration also substantially decreases. Resveratrol encapsulated in synthesized nanoparticles is referred to as nanoresveratrol. In the present study, nanoresveratrol effectiveness was studied through PTZ-induced seizures (PTZ-IS) and the increasing current electroshock (ICES) test. The efficacy of nanoresveratrol was further established using biochemical analysis, histopathological examinations, ELISA and real-time-PCR tests, and immunohistochemistry examination of the hippocampus of mice. Hence, this study is unique in the sense that it synthesized nanoresveratrol by using glutathione-coated collagen nanoparticles, followed by its application to treating seizures. On the basis of the study results, nanoresveratrol was found to be effective in preventing cognitive impairment in the mice and controlling epilepsy seizures to a greater extent than resveratrol. The proposed nanoformulation also reduces the concentration of resveratrol considerably. The present study results show that even 0.4 mg/kg of nanoresveratrol outperforms 40 mg/kg of resveratrol.


Assuntos
Epilepsia , Proteína HMGB1 , Nanopartículas , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Colágeno/efeitos adversos , Epilepsia/tratamento farmacológico , Glutationa , Hipocampo , Camundongos , Pentilenotetrazol/farmacologia , Resveratrol/farmacologia , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Receptor 4 Toll-Like
6.
Yale J Biol Med ; 95(1): 57-69, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35370490

RESUMO

Background: Renovascular hypertension elicits cardiac damage and remodeling. Two-kidney, one-clip (2K1C) is an experimental model used to study hypertension pathophysiology. In this model, the renin-angiotensin-system (RAS) is overactive due to renal artery stenosis, leading to cardiac remodeling. Redox mechanisms underlying RAS activation mediate hypertension-induced cardiovascular damage. Preclinical studies and clinical trials demonstrated resveratrol's protective effects in cardiovascular diseases, mainly attributed to its antioxidant properties. We hypothesized resveratrol alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor would be beneficial against cardiac damage caused by renovascular hypertension. Objective: We investigated the benefits of resveratrol against cardiac remodeling in 2K1C rats compared with captopril. Methods: Male Wistar rats underwent unilateral renal stenosis - 2K1C Goldblatt model of hypertension. Systolic Blood Pressure (SBP) was measured before and 6 weeks after surgery. Hypertensive 2K1C rats presented SBP≥160 mmHg. From the 6th week after the surgery, the animals received oral resveratrol (20 mg/kg), captopril (12 mg/kg), or their combination for 3 times per week for 3 weeks. Whole heart hypertrophy was evaluated. Histological assays assessed left ventricle hypertrophy and fibrosis. Results: Renovascular hypertension caused cardiac hypertrophy, accompanied by increased myocyte diameter and collagen deposition. Resveratrol reduced 2K1C rats' SBP and whole heart hypertrophy, independently of captopril. Resveratrol caused a higher reduction in ventricular hypertrophy than captopril. Collagen deposition was greater reduced by 2K1C treated only with resveratrol than with captopril alone or combined with resveratrol. Conclusion: Independent of captopril, resveratrol prompts cardioprotective effects on cardiomyocyte remodeling and fibrosis resulting from renovascular hypertension in 2K1C rats.


Assuntos
Hipertensão , Obstrução da Artéria Renal , Animais , Captopril/farmacologia , Humanos , Masculino , Ratos , Ratos Wistar , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/tratamento farmacológico , Resveratrol/farmacologia , Remodelação Ventricular/fisiologia
7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(4): 461-469, 2022 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-35426287

RESUMO

Objective: To investigate the effect of resveratrol (RES) on inflammation-induced cartilage endplate (CEP) degeneration, and its regulatory mechanism on high mobility group box-1 protein (HMGB1) signaling pathway. Methods: The intervertebral CEP cells of Sprague Dawley (SD) rats aged 3 weeks were extracted and identified by toluidine blue staining and immunofluorescence staining of rabbit anti-rat collagen type Ⅱ. The cell counting kit 8 (CCK-8) method was used to screen the optimal concentration of RES on intervertebral CEP cells. Gene chip analysis was used to determine the target of RES on intervertebral CEP cells. Interleukin 1ß (IL-1ß) was used to construct the intervertebral CEP cell degeneration model caused by inflammation and the 7-8-week-old SD rat intervertebral disc degeneration model, and pcDNA3.1-HMGB1 (pcDNA3.1) was used as the control of RES effect. Flow cytometry and TUNEL staining were used to detect the apoptotic rate of intervertebral CEP cells and rat intervertebral disc tissue cells, respectively. ELISA kit was used to detect the content of interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) in the cell supernatant and rat serum. Western blot was used to detect the expressions of HMGB1, extracellular signal-regulated protein kinase (ERK), phosphorylated ERK (p-ERK), B cell lymphoma/leukemia 2 gene (Bcl-2), and Bcl-2-associated X protein (Bax). Results: The extracted cells were identified as rat intervertebral CEP cells. CCK-8 method screened out the highest activity of intervertebral CEP cells treated with 30 µmol/L RES. The gene chip analysis confirmed that the HMGB1-ERK signal was the target of RES. Both cell experiments and animal experiments showed that RES treatment can significantly down-regulate the apoptosis rate of intervertebral CEP cells, inhibit the release of TNF-α, and increase the content of IL-10; and down-regulate the expressions of HMGB1, p-ERK, and Bax, and increase Bcl-2; and pcDNA3.1 could partially reverse these effects of RES, and the differences were all significant (P<0.05). Conclusion: RES can significantly inhibit the apoptosis of intervertebral CEP cells induced by inflammation, which is related to inhibiting the expression of HMGB1.


Assuntos
Proteína HMGB1 , Degeneração do Disco Intervertebral , Disco Intervertebral , Animais , Cartilagem/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Proteína HMGB1/farmacologia , Inflamação/metabolismo , Inflamação/patologia , Interleucina-10/metabolismo , Coelhos , Ratos , Ratos Sprague-Dawley , Resveratrol/metabolismo , Resveratrol/farmacologia , Transdução de Sinais , Sincalida/metabolismo , Sincalida/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
8.
Int J Mol Sci ; 23(7)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35409389

RESUMO

Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review has drawn attention to the axis between resveratrol and human microbiota, which plays a key role in maintaining an adequate immune response that can lead to different diseases when compromised. Resveratrol can also be an asset in new technologies, such as gene therapy. PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to find papers that matched our topic dating from 1 January 2017 up to 18 January 2022, with English-language restriction using the following Boolean keywords: ("resveratrol" AND "microbio*"). Eighteen studies were included as relevant papers matching the purpose of our investigation. Immune response, prevention of thrombotic complications, microbiota, gene therapy, and bone regeneration were retrieved as the main topics. The analyzed studies mostly involved resveratrol supplementation and its effects on human microbiota by trials in vitro, in vivo, and ex vivo. The beneficial activity of resveratrol is evident by analyzing the changes in the host's genetic expression and the gastrointestinal microbial community with its administration. The possibility of identifying individual microbial families may allow to tailor therapeutic plans with targeted polyphenolic diets when associated with microbial dysbiosis, such as inflammatory diseases of the gastrointestinal tract, degenerative diseases, tumors, obesity, diabetes, bone tissue regeneration, and metabolic syndrome.


Assuntos
Disbiose , Microbioma Gastrointestinal , Suplementos Nutricionais , Humanos , Obesidade/tratamento farmacológico , Resveratrol/farmacologia , Resveratrol/uso terapêutico
9.
Molecules ; 27(8)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35458574

RESUMO

Since COVID-19 has affected global public health, there has been an urgency to find a solution to limit both the number of infections, and the aggressiveness of the disease once infected. The main characteristic of this infection is represented by a strong alteration of the immune system which, day by day, increases the risk of mortality, and can lead to a multiorgan dysfunction. Because nutritional profile can influence patient's immunity, we focus our interest on resveratrol, a polyphenolic compound known for its immunomodulating and anti-inflammatory properties. We reviewed all the information concerning the different roles of resveratrol in COVID-19 pathophysiology using PubMed and Scopus as the main databases. Interestingly, we find out that resveratrol may exert its role through different mechanisms. In fact, it has antiviral activity inhibiting virus entrance in cells and viral replication. Resveratrol also improves autophagy and decreases pro-inflammatory agents expression acting as an anti-inflammatory agent. It regulates immune cell response and pro-inflammatory cytokines and prevents the onset of thrombotic events that usually occur in COVID-19 patients. Since resveratrol acts through different mechanisms, the effect could be enhanced, making a totally natural agent particularly effective as an adjuvant in anti COVID-19 therapy.


Assuntos
COVID-19 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Suplementos Nutricionais , Humanos , Resveratrol/farmacologia , Resveratrol/uso terapêutico
10.
Molecules ; 27(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35458766

RESUMO

Ischemia-reperfusion myocardial damage is a paradoxical tissue injury occurring during percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients. Although this damage could account for up to 50% of the final infarct size, there has been no available pharmacological treatment until now. Oxidative stress contributes to the underlying production mechanism, exerting the most marked injury during the early onset of reperfusion. So far, antioxidants have been shown to protect the AMI patients undergoing PCI to mitigate these detrimental effects; however, no clinical trials to date have shown any significant infarct size reduction. Therefore, it is worthwhile to consider multitarget antioxidant therapies targeting multifactorial AMI. Indeed, this clinical setting involves injurious effects derived from oxygen deprivation, intracellular pH changes and increased concentration of cytosolic Ca2+ and reactive oxygen species, among others. Thus, we will review a brief overview of the pathological cascades involved in ischemia-reperfusion injury and the potential therapeutic effects based on preclinical studies involving a combination of antioxidants, with particular reference to resveratrol and quercetin, which could contribute to cardioprotection against ischemia-reperfusion injury in myocardial tissue. We will also highlight the upcoming perspectives of these antioxidants for designing future studies.


Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Intervenção Coronária Percutânea , Traumatismo por Reperfusão , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Quercetina/farmacologia , Quercetina/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Resveratrol/farmacologia , Resveratrol/uso terapêutico
11.
Biomed Res Int ; 2022: 7140961, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386302

RESUMO

Purpose: The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model. Methods: A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed. Results: RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-α, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. Conclusion: SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-κB signaling pathway.


Assuntos
Transplante de Rim , Traumatismo por Reperfusão , Animais , Citocinas/metabolismo , Humanos , Rim/metabolismo , Transplante de Rim/efeitos adversos , NF-kappa B/metabolismo , Estresse Oxidativo , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Traumatismo por Reperfusão/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Transdução de Sinais , Sirtuína 1/metabolismo
12.
J Healthc Eng ; 2022: 9705144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399833

RESUMO

To investigate the effects and mechanisms of resveratrol on glucolipid metabolism in diabetic humans. In this paper, we introduced the knowledge discovery theory into the data processing of the factors related to the pathogenesis of type 2 diabetes for the first time, and identified valid, potentially useful, and understandable pathogenesis patterns from a large amount of measured data. A data mining C4.5 algorithm was used to classify 17072 validated cross-sectional health survey data from the whole population according to the characteristics of type ρ diabetes data. A human model of diabetes mellitus was prepared by high sugar and high fat diet plus low dose streptozotocin (STZ, 35 mg/kg) and randomly grouped into four groups: the normal control group, the model group, the resveratrol group, and the pioglitazone group. 8 animals in each group were treated with the corresponding drugs for 8 weeks. Hepatic steatosis and damage were significantly reduced compared with the model group as observed by HE staining. Resveratrol has obvious effects on regulating glucolipid metabolism, and its mechanism of action is associated with its ability to increase the antioxidant activity of the body, activate the Akt signaling pathway, and improve liver pathological damage.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Animais , Apoptose , Proliferação de Células , Estudos Transversais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Humanos , Descoberta do Conhecimento , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Estreptozocina/farmacologia , Estreptozocina/uso terapêutico
13.
Sci Rep ; 12(1): 6403, 2022 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35431315

RESUMO

The biocompatible hybrid Zeolitic imidazolate framework-8 (ZIF-8)/structured silica nanocomposite can be loaded with antioxidants such as curcumin and resveratrol to offer multiple advantages of drug functionalization and structural stability. blastocystosis, an enteric parasite, has various outcomes and its treatment includes drugs which have side effects and do not result in a full cure. We aimed to design novel biocompatible nanocomposites containing natural antioxidant, resveratrol or curcumin and ZIF-8/mesoporous silica. We also assessed their anti-blastocystosis activities as bioactive novel nanocomposites. The nano-silica (MCM-41 and KIT-6) was synthesized using a hydrothermal technique and made composite with ZIF-8 using an ultrasonic technique. The antioxidants, curcumin and resveratrol, were loaded over ZIF-8/MCM-41 and ZIF-8/KIT-6 using a rotary evaporator technique to form novel nanocomposites with bioactive properties. The formulated nanocomposites were characterized. To test their biological activity, suspension of cultured blastocystosis cysts (subtype 3) were exposed to increasing concentrations of nanocomposites and the minimal lethal concentration of each nanocomposite was calculated. The bioactive nanocomposites (ZIF-8/KIT-6, ZIF-8/KIT-6/Resveratrol and ZIF-8/MCM-41/Curcumin) were formulated. Anti-blastocystosis activity of the tested nanocomposites was both dose and time dependent. ZIF-8/KIT-6/Resveratol showed the maximum percentage of growth inhibition (~ 100%) at a concentration of 500 µg/ml after 5 h of exposure. More than 90% of blastocystosis cysts' growth was significantly inhibited at all concentrations of ZIF-8/MCM-41/Curcumin, with different times of exposure, while it occurred only at the highest concentration of ZIF-8/KIT-6 (800 µg/ml). Using cheap, simple, reproducible and scalable techniques, we nano-formulated innovative bioactive nanocomposites, by incorporating the bioactive ZIF-8 (Zn2+ with imidazole), structured mesosilica and natural antioxidant compounds, curcumin or resveratrol, to generate multifunctional modalities. These eco-friendly, naturally based, safe, economical, biocompatible, and bioavailable nanocomposites are potential nanotherapeutics. The anti-blastocystosis results of these three nanocomposites indicate their potentially promising innovative and safe use as alternative Blastocystosis therapies.


Assuntos
Curcumina , Cistos , Nanocompostos , Zeolitas , Antioxidantes/farmacologia , Curcumina/farmacologia , Humanos , Nanocompostos/química , Resveratrol/farmacologia , Dióxido de Silício/química , Zeolitas/química , Zeolitas/farmacologia
14.
Molecules ; 27(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35408747

RESUMO

trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis-resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations.


Assuntos
Glicerol , Isomerismo , Fenantrenos , Resveratrol/química , Resveratrol/farmacologia , Solventes/química
15.
Biol Trace Elem Res ; 200(5): 2283-2297, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35384580

RESUMO

Diabetes mellitus induces optic nerve injury via the excessive generation of mitochondria reactive free oxygen radical (mitROS). TRPM2 channel is activated by mitROS, although it is inhibited by selenium (Se) and resveratrol (RSV). The activation of TRPM2 induces apoptosis and oxidative injury in the optic nerve. The inhibition of TRPM2 may decrease the optic nerve injury action of diabetes mellitus after the treatments of Se and RSV. Present study aimed to investigate the protective actions of Se and RSV on the excessive Ca2+ influx and mitROS generation-mediated optic nerve oxidative injury via the modulation of TRPM2. Fifty-six C57BL/6j male mice were divided into seven groups as control, Se, RSV, streptozotocin (STZ), STZ + Se, STZ + RSV, and STZ + Se + RSV. The STZ-mediated stimulation of TRPM2 increased the cytosolic Ca2+, lipid peroxidation, mitROS, cytosolic ROS, apoptosis, caspase-3, caspase-8, and caspase-9 concentrations in the mice, although their concentrations were decreased in the optic nerve by the treatments of Se and RSV. The STZ-induced decrease of optic nerve viability, glutathione, glutathione peroxidase, vitamin A, and vitamin E concentrations was also upregulated by the treatments of Se and RSV. The STZ-induced increase of TRPM2, PARP-1, caspase-3, and caspase-9 protein band expressions was diminished by the treatments of Se and RSV. In conclusion, STZ induced the optic nerve oxidative injury and apoptosis via the upregulation of TRPM2 stimulation, although the treatments of Se and RSV decreased the injury and apoptosis via the downregulation of TRPM2 activity.


Assuntos
Diabetes Mellitus , Traumatismos do Nervo Óptico , Doenças Retinianas , Selênio , Canais de Cátion TRPM , Animais , Apoptose , Cálcio/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/farmacologia , Selênio/metabolismo , Selênio/farmacologia , Canais de Cátion TRPM/metabolismo
16.
Biomolecules ; 12(4)2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35454157

RESUMO

BACKGROUND: Preventing delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) remains an important therapeutic target. Preconditioning stimulates multiple endogenous protective mechanisms and may be a suitable treatment for DCI following SAH. We here compare remote limb conditioning with resveratrol conditioning in a clinically relevant SAH model. METHODS: We produced a SAH in 39 male Sprague Dawley rats using a single injection model. Animals were randomized to four groups: repetitive limb conditioning with a blood pressure cuff, sham conditioning, intraperitoneal resveratrol (10 mg/kg) or intraperitoneal vehicle administered at 24, 48 and 72 h after SAH. On day 4 neurological and behavioral scores were obtained, and animals were euthanized. The cross-sectional area of the basilar artery was measured at the vertebrobasilar junction, and at the mid and distal segments. Hippocampal cells were counted in both hemispheres and normalized per mm length. We compared true limb preconditioning with sham conditioning and resveratrol with vehicle preconditioning. RESULTS: The cross-sectional area of the mid-basilar artery in the true limb preconditioning group was significantly larger by 43% (p = 0.03) when compared with the sham preconditioning group. No differences in the cross-sectional area were found in the resveratrol-treated group when compared to the vehicle-treated group. We found no differences in the neuro score, behavioral score, and in mean hippocampal neuron counts between the groups. CONCLUSION: We found beneficial vascular effects of remote limb preconditioning on SAH-induced basilar artery vasoconstriction. Our findings support further studies of limb preconditioning as a potential treatment after SAH.


Assuntos
Isquemia Encefálica , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Roedores , Hemorragia Subaracnóidea/tratamento farmacológico , Vasoespasmo Intracraniano/tratamento farmacológico , Vasoespasmo Intracraniano/prevenção & controle
17.
Drug Deliv ; 29(1): 1122-1131, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35380089

RESUMO

Smoke bombs are often used in military/fire training, which can produce a large amount of zinc chloride (ZnCl2) smoke. Inhalation of ZnCl2 smoke usually causes acute lung injury (ALI) that would likely develop to acute respiratory distress syndrome (ARDS). However, there is no effective prevention or treatment strategy for the smoke-induced ALI. Resveratrol (RES) is a natural polyphenol with good anti-inflammatory and anti-apoptotic activities, but its low solubility, stability, and bioavailability restrict its clinical application. In this study, an inhalable RES formulation composed of RES-ß-cyclodextrin inclusion complexes (RES-ß-CD) was prepared for the prevention of ZnCl2 smoke-induced ALI. RES-ß-CD powders had a small mass median aerodynamic diameter of 3.61 µm and a high fine particle fraction of 38.84%, suitable for pulmonary inhalation. RES-ß-CD exhibited low BEAS-2B cytotoxicity. Pulmonary delivery of RES-ß-CD to mice remarkably prevented the smoke-induced ALI with downregulation of TNF-α, IL-1ß, STAT3, and GATA3, and upregulation of T-bet and Foxp3. RES-ß-CD protected the respiratory function, percutaneous oxygen saturation, physical activity, lung capillary integrity, and lung liquid balance, alleviating inflammation and apoptosis. Pulmonary delivery of the positive drug, budesonide (BUD), also alleviated the smoke-induced ALI by reduction of inflammation and cell apoptosis. RES-ß-CD exhibited the regulation of the Th1/Th2 and Treg/Th17 balances, while BUD did not show any effect on immune balances. In conclusion, pulmonary delivery of RES-ß-CD is a promising anti-inflammatory and anti-apoptosis strategy for the prevention of ZnCl2 smoke-induced ALI by direct lung drug distribution and regulation of immune balance.


Assuntos
Lesão Pulmonar Aguda , beta-Ciclodextrinas , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Animais , Cloretos , Pulmão , Camundongos , Resveratrol/farmacologia , Fumaça , Compostos de Zinco
18.
Nutrients ; 14(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35458194

RESUMO

Chronic hyperglycemia contributes to vascular complications in diabetes. Resveratrol exerts anti-diabetic and anti-platelet action. This study aimed to evaluate the effects of resveratrol on metabolism and the function of blood platelets under static and in in vitro flow conditions in patients with type 2 diabetes. Blood obtained from 8 healthy volunteers and 10 patients with type 2 diabetes was incubated with resveratrol and perfused over collagen-coated capillaries. Isolated blood platelets were incubated with resveratrol and activated by collagen to assess platelet function, metabolism, ATP release, TXA2 production, lipid peroxidation, and gluthatione content. In the type 2 diabetes group, plasma glucose and fructosamine concentrations were significantly higher than in the healthy group. In in vitro studies, collagen-induced thrombi formation in the blood of diabetic patients was 33% higher than in the healthy group. Resveratrol reduced thrombi by over 50% in the blood of healthy and diabetic patients. TXA2 production was 47% higher in diabetic platelets than in the healthy group. Resveratrol reduced TXA2 release by 38% in healthy platelets and by 79% in diabetic platelets. Resveratrol also reduced the activities of enzymes responsible for glycolysis and oxidative metabolism in the platelets of both groups. These data indicate that the resveratrol-induced inhibition of platelet metabolism and TXA2 release may lead to a reduction of platelet function and thrombus formation in patients with type 2 diabetes. Therefore, resveratrol may be beneficial to prevent vascular complications as a future complementary treatment in aspirin-resistant diabetic patients.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Agregação Plaquetária , Resveratrol , Trombose , Plaquetas/metabolismo , Doenças Cardiovasculares/metabolismo , Colágeno/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Agregação Plaquetária/fisiologia , Resveratrol/metabolismo , Resveratrol/farmacologia , Trombose/metabolismo , Tromboxano A2
19.
J Tradit Chin Med ; 42(2): 176-186, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35473337

RESUMO

OBJECTIVE: To investigate the protective effect of resveratrol on cardiomyocytes after hypoxia/ reoxygenation intervention based on PTEN-induced putative kinase protein 1/Parkinson disease protein 2 (PINK1/PARKIN) signaling pathway. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide was used to detect the effect of resveratrol on the viability of H9C2 cells; the hypoxia/ reoxygenation (H/R) model was established in tri-gas incubator; 2', 7'-Dichlorofluorescin diacetate staining was used to measure the content of reactive oxygen species (ROS); the changes of mitochondrial membrane potential was determined by 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide staining; the changes of mitochondrial respiratory chain complex activity was evaluated by enzyme activity kits; flow cytometry was used to detect the ratio of apoptotic cells; transmission electron microscope was used to observe the ultrastructure of H9C2 cells; Western blot was used to detect the protein changes of mitochondrial 20 kDa outer membrane protein (TOM20), translocase of inner mitochondrial membrane 23 (TIM23), presenilins associated rhomboid-like protein (PARL), PINK1, PARKIN and mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), phosphotyrosine independent ligand for the Lck SH2 domain of 62 kDa (P62), microtubule-associated protein 1 light chain 3 beta (LC3B); the mRNA levels of PINK1 and PARKIN was detected by quantitative polymerase chain reaction; immunoprecipitation assay was used to detect the interaction between PARKIN and Ubiquitin. RESULTS: Resveratrol could inhibit the proliferation of H9C2 cells in a time- and concentration- dependent manner; however, pretreatment with low cytotoxic resveratrol could reduce the H/R-induced increase in cellular ROS levels, alleviate the loss of mitochondrial membrane potential induced by H/R, inhibit H/R-induced apoptosis of H9C2 cells, and protect the mitochondrial structure and respiratory chain of H9C2 cells from H/R damage. Resveratrol could further increase the levels of p62, PINK1, PARKIN protein, the expression of PINK1, PARKIN mRNA and the ratio of LC3BⅡ/LC3BⅠin H/R-induced H9C2 cells, inhibit the interaction between PARKIN and Ubiquitin in H/R-induced H9C2 cells, and further reduce the expression of TOM20,TIM23, PARL, Mfn1 and Mfn2 protein in H/R-induced H9C2 cells. The effect of resveratrol is consistent with that of autophagy activator on H/R-induced H9C2 cells. CONCLUSIONS: Resveratrol can protect H9C2 cells from H/R injury, which may be related to resveratrol promoting mitochondrial autophagy by activating PINK1/PARKIN signaling pathway.


Assuntos
Miócitos Cardíacos , Doença de Parkinson , Animais , Autofagia , Humanos , Hipóxia/metabolismo , Doenças Mitocondriais , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/metabolismo , Resveratrol/farmacologia , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/farmacologia , Ubiquitinas/metabolismo , Ubiquitinas/farmacologia
20.
Biochem Pharmacol ; 199: 115024, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35367197

RESUMO

The efficacy of poly (ADP-ribose) polymerase inhibitors (PARPi) is largely limited to the homologous recombination (HR) deficient cancers. Therefore, there is a necessity to explore novel drug combinations with PARPi to enhance its anti-cancer activity in HR-proficient cancers. By analysing the patient data in cBioPortal, we found copy number amplification of PARP1 in âˆ¼ 22.8% of breast cancers. PARP1 upregulation has been correlated with unfavourable outcome with PARPi treatment. To overcome this adversity, we explored the effect of resveratrol, a natural molecule chemosensitizer, in enhancing the effects of the third generation PARPi, talazoparib (BMN673), against breast adenocarcinoma. Our results show that resveratrol effectively sensitized talazoparib induced cell death in HR proficient and BRCA wild-type breast cancer cells in vitro. Mechanistically, resveratrol caused dysregulation of cell cycle and enhanced talazoparib-induced double strand breaks (DSBs), leading to abnormal mitotic progression culminating in mitotic catastrophe. Intriguingly, our results showed potential of resveratrol in dual-inhibition of AKT-signalling and autophagy flux to impair HR-mediated DSB-repair in breast cancer cells. By using EGFP-LC3 and tf-LC3 (mRFP-EGFP-LC3) expressing breast cancer cells, we found that resveratrol attenuates fusion of autophagosome and lysosome though induction of lysosomal-membrane-permeabilization (LMP). The combination of resveratrol and talazoparib effectively reduced cell proliferation in the high-density cell proliferation assay and also led to tumour volume reduction in vivo pre-clinical SCID-mice model. The combination caused no or minimal cytotoxicity in three different normal cell lines in vitro. Taken together, our work proposes the usage of resveratrol as a chemosensitizer along with talazoparib for targeting HR-proficient breast cancers in clinical settings.


Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos SCID , Ftalazinas/farmacologia , Ftalazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
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