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Resveratrol AND Sirtuins

Yulong Chen, Cangbao Xu, Yahui Wei, Yaping Zhang, Ailan Cao
Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration-dependently relaxed endothelium-intact superior mesenteric artery rings pre-contracted by phenylephrine hydrochloride (Emax, 97...
October 2016: Experimental and Therapeutic Medicine
Ala Abdelali, Maie Al-Bader, Narayana Kilarkaje
Diabetes induces oxidative stress, DNA damage and alters several intracellular signaling pathways in organ systems. This study investigated modulatory effects of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip) to Streptozotocin-induced T1DM adult male Wistar rats from day 22-42 resulted in recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the testis and spermatozoa, and DNA double-strand breaks in the testis...
September 27, 2016: Toxicology and Applied Pharmacology
Shao-Yu Yang, Shuei-Liong Lin, Yung-Ming Chen, Vin-Cent Wu, Wei-Shiung Yang, Kwan-Dun Wu
Activation of sirtuin 1 (Sirt1) attenuates unilateral ureteral obstruction (UUO)-induced inflammation and fibrosis, suggesting that Sirt1 may prevent tubulointerstitial fibrosis. In this study, we explored changes in the expression of Sirt1 in the kidneys of UUO-treated rats and evaluated the effects of Sirt1 activation or inhibition on renal pathology and mediators of UUO pathogenesis, especially angiotensin II and nuclear factor (NF)-κB, in rats and rat renal fibroblasts. Sirt1 expression increased in the obstructed kidney but not in the contralateral kidney and was mainly detected in tubulointerstitial cells...
2016: Scientific Reports
Chun-Yan Shen, Jian-Guo Jiang, Li Yang, Da-Wei Wang, Wei Zhu
Aging, a puzzling question in the medical field, is a multifactorial process that results in a progressive functional decline at cellular, tissue, and organismal levels. Although it is impossible to prevent aging, slowing down the pace of aging is entirely possible to achieve. Traditional Chinese medicine (TCM) is characterized by the nourishing of life, its role in anti-aging is getting more and more attention. This article summarizes the natural products from TCM that are reported to have anti-aging effects in the past two decades...
September 23, 2016: British Journal of Pharmacology
Luana Naia, Tatiana R Rosenstock, Ana M Oliveira, Sofia I Oliveira-Sousa, Gladys L Caldeira, Catarina Carmo, Mário N Laço, Michael R Hayden, Catarina R Oliveira, A Cristina Rego
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent lysine deacetylase that regulates longevity and enhances mitochondrial metabolism. Both activation and inhibition of SIRT1 were previously shown to ameliorate neuropathological mechanisms in Huntington's disease (HD), a neurodegenerative disease that selectively affects the striatum and cortex and is commonly linked to mitochondrial dysfunction. Thus, in this study, we tested the influence of resveratrol (RESV, a SIRT1 activator) versus nicotinamide (NAM, a SIRT1 inhibitor) in counteracting mitochondrial dysfunction in HD models, namely striatal and cortical neurons isolated from YAC128 transgenic mice embryos, HD human lymphoblasts, and an in vivo HD model...
September 2, 2016: Molecular Neurobiology
Nannan Zhang, Zhongchi Li, Kang Xu, Yanying Wang, Zhao Wang
Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence...
2016: Biological & Pharmaceutical Bulletin
B Raghunath Reddy, Swati Maitra, Priya Jhelum, K Praveen Kumar, Pankaj K Bagul, Gagandeep Kaur, Sanjay K Banerjee, Arvind Kumar, Sumana Chakravarty
Hyperglycaemia in diabetes is either caused by reduced availability of insulin (type 1 diabetes, T1D) or insulin resistance to the cells (type 2 diabetes, T2D). In recent years, the prevalence of T2D has increased to an alarming proportion, encompassing 95 percent of the total diabetic burden, probably due to economy-driven changes in lifestyle. Recent epidemiological studies show comorbid depression, anxiety and related mental illness. To explore the molecular mechanisms underlying this comorbid conditions, we used Sprague-Dawley rats on high-fructose diet for 8 weeks to induce prediabetic condition...
September 2016: Journal of Biosciences
Zhengtang Qi, Jie Xia, Xiangli Xue, Qiang He, Liu Ji, Shuzhe Ding
Nicotinamide (NAM), or vitamin B3, is an essential coenzyme for ATP synthesis and an inhibitor of sirtuin 1. Recently, conflicting results were reported regarding the treatment of NAM in type 2 diabetes and obesity. The aim of this study was to determine whether and how long-term treatment with NAM at lower dose would affect insulin sensitivity in mice fed chow diet. We treated mice with NAM (100 mg/kg/day) and normal chow for 8 weeks. Strikingly, NAM induced glucose intolerance and skeletal muscle lipid accumulation in nonobese mice...
October 2016: Journal of Nutritional Biochemistry
Michael S Bonkowski, David A Sinclair
The sirtuins (SIRT1-7) are a family of nicotinamide adenine dinucleotide (NAD(+))-dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing. Mice engineered to express additional copies of SIRT1 or SIRT6, or treated with sirtuin-activating compounds (STACs) such as resveratrol and SRT2104 or with NAD(+) precursors, have improved organ function, physical endurance, disease resistance and longevity. Trials in non-human primates and in humans have indicated that STACs may be safe and effective in treating inflammatory and metabolic disorders, among others...
August 24, 2016: Nature Reviews. Molecular Cell Biology
Ana García-Aguilar, Carlos Guillén, Mark Nellist, Alberto Bartolomé, Manuel Benito
There is a growing evidence of the role of protein acetylation in different processes controlling metabolism. Sirtuins (histone deacetylases nicotinamide adenine dinucleotide-dependent) activate autophagy playing a protective role in cell homeostasis. This study analyzes tuberous sclerosis complex (TSC2) lysine acetylation, in the regulation of mTORC1 signaling activation, autophagy and cell proliferation. Nicotinamide 5mM (a concentration commonly used to inhibit SIRT1), increased TSC2 acetylation in its N-terminal domain, and concomitantly with an augment in its ubiquitination protein status, leading to mTORC1 activation and cell proliferation...
August 16, 2016: Biochimica et Biophysica Acta
Guijuan Feng, Ke Zheng, Donghui Song, Ke Xu, Dan Huang, Ye Zhang, Peipei Cao, Shuling Shen, Jinlong Zhang, Xingmei Feng, Dongmei Zhang
Dental pulp stem cells (DPSCs), as one type of mesenchymal stem cells (MSCs), have the capability of self-renewal and differentiating along the various directions, including osteogenic, chondrogenic, neurogenic, and adipogenic. We previously study and found that tumor necrosis factor-α (TNF-α) promoted osteogenic differentiation of human DPSCs via the Wnt/β-catenin signaling pathway in low concentration while inhibited that in high concentration. In the abovementioned process, we found that sirtuin-1 (SIRT1) had the same change compared with the characteristic protein of bone formation, such as bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), and collagen I (COL1)...
August 16, 2016: In Vitro Cellular & Developmental Biology. Animal
Meredith L Sosulski, Rafael Gongora, Carol Feghali-Bostwick, Joseph A Lasky, Cecilia G Sanchez
Oxidative stress leads to alveolar epithelial cell injury and fibroblast-myofibroblast differentiation (FMD), key events in the pathobiology of pulmonary fibrosis (PF). Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase regulator of antioxidant response and mitochondrial homeostasis. Here, we demonstrate reduced SIRT3 expression in the lungs of old mice compared to young mice, as well as in two murine models of PF. The analysis of the pattern of SIRT3 expression in the lungs of patients with PF revealed low SIRT3 staining within the fibrotic regions...
August 13, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Haidong Jin, Hui Chen, Kehe Yu, Jingdong Zhang, Bin Li, Ningyu Cai, Jun Pan
The present study assessed the mechanism by which resveratrol (Res) inhibits the growth of SW1353 chondrosarcoma cells and examined whether sirtuin 1 (Sirt1) activation affects phosphorylation within the signal transduction and activator of transcription 3 (STAT3) signaling pathway. The present study used SW1353 chondrosarcoma cells in the logarithmic phase of growth (control and treatment groups). The latter group was treated with Res at 25 and 50 µmol/l for 24 h, and cell viability, proliferation and apoptosis were analyzed using the cell counting kit‑8 assay, colony counting and Hoechst staining, respectively...
September 2016: Molecular Medicine Reports
Juhyun Song, Mira Jun, Mok-Ryeon Ahn, Oh Yoen Kim
BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol...
August 2016: Nutrition Research and Practice
Mi-Hua Liu, Jian Shan, Jian Li, Yuan Zhang, Xiao-Long Lin
Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it can induce severe cytotoxicity, which limits its clinical application. In the present study, the effects of resveratrol (RES) on sirtuin 1 (SIRT1) activation in mediating DOX-induced cytotoxicity in H9c2 cardiac cells was investigated. H9c2 cells were exposed to 5 µM DOX for 24 h to establish a model of DOX cardiotoxicity. Apoptosis of H9c2 cardiomyocytes was assessed using the MTT assay and Hoechst nuclear staining. The results demonstrated that pretreating H9c2 cells with RES prior to the exposure of DOX resulted in increased cell viability and a decreased quantity of apoptotic cells...
August 2016: Experimental and Therapeutic Medicine
Jessica L Fry, Leona Al Sayah, Robert M Weisbrod, Isabelle Van Roy, Xiang Weng, Richard A Cohen, Markus M Bachschmid, Francesca Seta
Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed a high-fat, high-sucrose (HFHS) diet, serving as a model of human metabolic syndrome, and it is associated with activation of proinflammatory and oxidant pathways in vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) is an NAD(+)-dependent deacetylase regulated by the cellular metabolic status. Our goal was to study the effects of VSM SirT1 on arterial stiffness in the context of diet-induced metabolic syndrome. Overnight fasting acutely decreased arterial stiffness, measured in vivo by pulse wave velocity, in mice fed HFHS for 2 or 8 months, but not in mice lacking SirT1 in VSM (SMKO)...
September 2016: Hypertension
Seda Sultan Uğurel, Nilay Kuşçu, Çiler Çelik Özenci, Selvinaz Dalaklıoğlu, Arda Taşatargil
BACKGROUND: The cardiovascular benefits of Resveratrol (RVT) have been well established by previous experimental and clinical studies. AIMS: The goal of this study was to test the effectiveness of RVT administration on the impaired endothelial function induced by lipopolysaccharide (LPS), and to elucidate the role of endothelial nitric oxide synthase (eNOS)/Sirtuin 1 (SIRT1) pathway. STUDY DESIGN: Animal experiment. METHODS: Endotoxemia was induced by intraperitoneal injection of 10 mg/kg LPS, and the thoracic aorta was isolated six hours later...
March 2016: Balkan Medical Journal
Caio Yogi Yonamine, Erika Pinheiro-Machado, Maria Luiza Michalani, Helayne Soares Freitas, Maristela Mitiko Okamoto, Maria Lucia Corrêa-Giannella, Ubiratan Fabres Machado
BACKGROUND: Resveratrol is a natural polyphenol that has been proposed to improve glycemic control in diabetes, by mechanisms that involve improvement in insulin secretion and activity. In type 1 diabetes (T1D), in which insulin therapy is obligatory, resveratrol treatment has never been investigated. The present study aimed to evaluate resveratrol as an adjunctive agent to insulin therapy in a T1D-like experimental model. METHODS: Rats were rendered diabetic by streptozotocin (STZ) treatment...
2016: Nutrition & Metabolism
Cláudia M Deus, Teresa L Serafim, Silvia Magalhães-Novais, Andreia Vilaça, Ana C Moreira, Vilma A Sardão, Susana M Cardoso, Paulo J Oliveira
Sirtuins regulate several processes associated with tumor development. Resveratrol was shown to stimulate sirtuin 1 and 3 (SIRT1/3) activities and to result in cytotoxicity for some tumor types. The relationship between modulation of sirtuin activities, cellular metabolic remodeling and resveratrol cytotoxicity mechanism on breast cancer cells is still an open question. Here, we evaluated whether sirtuin 1 and 3 are involved in resveratrol toxicity and whether resveratrol leads to a metabolic remodeling and cell differentiation...
June 29, 2016: Archives of Toxicology
K Shimizu, S Miyagi, K Miyazawa, K Maida, T Kashiwadate, Y Hara, M Goto, N Kawagishi, N Ohuchi
BACKGROUND: Successful liver transplantation from non-heart-beating donors (NHBDs) might enlarge donor source. Some studies have reported that resveratrol (RES), an activator of sirtuins, has cytoprotective effects on ischemia-reperfusion (I/R) injury. The purpose of this study was to investigate the effects of RES on warm I/R injury in rats. METHODS: Male Wister rats were divided into 5 groups: (1) the heart-beating (HB) group, whose livers were retrieved from HB donors; (2) the NHB group, whose livers were retrieved under apnea-induced NHB conditions; (3) the ethanol group, retrieved in the same manner as the NHB group with ethanol (10 μL) as a solvent; (4) the RES-1 group, retrieved in the same manner as the NHB group and pretreated with RES (0...
May 2016: Transplantation Proceedings
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