NAD AND resveratrol AND sirtuin

NAD+ -dependent histone deacetylases (sirtuins 1-7) have been shown to be involved in various pathophysiological conditions including their involvement in cardiovascular, cancerous, neurodegenerative, immune dysregulation and inflammatory conditions. This study investigates the inflammomodulatory potential of resveratrol (RES), a sirtuin activator and sirtinol (SIR), a sirtuin inhibitor in lipopolysaccharide (LPS)-induced model of sickness behaviour in mice. Male Swiss albino mice were divided into five groups (n = 6) consisting of saline (SAL), LPS, RES, SIR, and fluoxetine (FLU) respectively, each group except LPS was prepared by intraperitoneally (i...

BACKGROUND: Acute kidney injury (AKI), a common multidisciplinary diagnostic clinical critical illness, eventually causes end-stage renal disease (ESRD). Although many clinical measures have been taken to prevent or treat AKI, high morbidity and death rates were recorded. Therefore, in-depth pathogenesis study and search for new therapeutic targets are in demand. Interestingly, the suirtuins family showed a significant protective effect in AKI. Sirtuins (SIRT1-7) is a family of seven proteins with NAD+ -dependent type III histone deacetylase activity...

Sirtuins (SIRTs) are described as NAD+ -dependent deacetylases, also known as class III histone deacetylases. So far, seven sirtuin genes (SIRTS 1-7) have been identified and characterized in mammals and are also known to occur in bacteria and eukaryotes. SIRTs are involved in various biological processes, including endocrine system, apoptosis, aging and longevity, diabetes, rheumatoid arthritis, obesity, inflammation, etc. Among them, the best-characterized one is SIRT1. Small molecules seem to be the most effective SIRT modulators...

The nutrient sensing nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) regulates the host response to short-term fasting by inducing hepatic transcriptional programming of ketogenesis, fatty acid oxidation and transport, and autophagy. This adaptation is ineffective in chronically undernourished individuals, among whom dyslipidemia and hepatic steatosis are common. We recently reported that hepatic PPARα protein is profoundly depleted in male mice undernourished by a low-protein, low-fat diet...

NAD+ -dependent deacetylase SIRT1 regulates many different biological processes, thus being involved in pathogenic conditions such as metabolic diseases, neurogenerative disorders and cancer. Notably, experimental evidence underlined that the activation of SIRT1 had promising cardioprotective effects. Consequently, many efforts have been so far devoted to finding new SIRT1 activators, both derived from natural sources or prepared by synthetic procedures. Herein, we discovered new SIRT1-activating derivatives, characterized by phenolic rings spaced by sulfur, nitrogen or oxygen-based central linkers...

Obesity is a major current public health problem of global significance. A progressive sperm quality decline, and a decline in male fertility, have been reported in recent decades. Several studies have reported a strict relationship between obesity and male reproductive dysfunction. Among the many mechanisms by which obesity impairs male gonadal function, sirtuins (SIRTs) have an emerging role. SIRTs are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that play a role in gene regulation, metabolism, aging, and cancer...

HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain-blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction...

BACKGROUND: 4-hexylresorcinol (4HR) has been shown to have anti-oxidant activity similar to that of resveratrol. As resveratrol increases sirtuin (SIRT) activity, 4HR might behave similarly to resveratrol. METHOD: In this study, the expression levels of SIRT1, SIRT3, and SIRT6 were evaluated after 4HR administration (1-100 μM). As NAD+ is a substrate for SIRTs, its levels with SIRT activity were also studied. RESULTS: In the results, SIRT3 (100 μM at 24 h) and SIRT6 (1-100 μM at 24 h and 10 μM at 8 h) were shown to have significantly higher expression levels compared to untreated control (p < 0...

Sirtuin 1 (SIRT1) of largemouth bass ( Micropterus salmoides ) was cloned and characterized in the present study and the influence of SIRT1 activation induced by resveratrol inclusion on the expression of genes related to lipid metabolism and antioxidation was also investigated. The SIRT1 of largemouth bass, with full-length cDNA sequence of 3395bp encoding 695 amino acids, was mainly expressed in gonad, heart and liver. The analysis of multiple sequence alignment revealed that, in accordance with other species, SIRT1 of largemouth bass contained highly conserved substrate-binding site and NAD+ binding site...

Polyphenols are chemopreventive through the induction of nuclear factor erythroid 2 related factor 2 (Nrf2)-mediated proteins and anti-inflammatory pathways. These pathways, encoding cytoprotective vitagenes, include heat shock proteins, such as heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1), as well as glutathione redox system to protect against cancer initiation and progression. Phytochemicals exhibit biphasic dose responses on cancer cells, activating at low dose, signaling pathways resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol (HT) or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol...

BACKGROUND: Progressive tubulointerstitial fibrosis (TIF) is the final common pathway leading to ESRD. There is an urgent need to develop effective approaches slowing the progression of TIF. Previous studies showed that systemic supplementation of nicotinamide (NAM) increases renal NAD+ and reverses ischemic-reperfusion induced acute renal injury. However, the role and mechanism of NAM in TIF has been unclear. METHODS: In vivo, we injected NAM (0.25 mg/g) 3 days before unilateral ureter obstruction (UUO) till day 7 post-operation...

Healthy aging is not the result of a single factor. Genes, dietary choices/options, exercise, and environmental exposures all play a role. A family of seven nicotinamide adenine dinucleotide (NAD)-dependent sirtuin proteins are very involved in various metabolic functions, such as glucose and fat regulation, and polymorphisms in these genes have been associated with the development of obesity, type 2 diabetes, cancer, cardiovascular disease, and longevity. Nutraceuticals (i.e., resveratrol, quercetin, kaempferol, and curcumin) and other therapies (i...

INTRODUCTION: Sirtuins, NAD-dependent protein deacetylases, require NAD+ for enzymatic activity. Recent research has indicated that sirtuins have a key role in the regulation of gene expression, the cell cycle, apoptosis, neurodegeneration and several age-related diseases. In mammals, there are seven sirtuin isoforms (SIRT-1-7) that catalyze specific lysine substrate deacetylation. AREAS COVERED: This review explains the current information on the structure, function and importance of sirtuin modulators...

Cerebral ischemia (CI) is a severe cause of neurological dysfunction and mortality. Sirtuin-1 (Silent information regulator family protein 1, SIRT1), an oxidized nicotinamide adenine dinucleotide (NAD+ )-dependent protein deacetylase, plays an important role in protection against several neurodegenerative disorders. The present study aims to investigate the protective role of SIRT1 after CI in experimental young and aged rats and humans. Also, the study examines the possible regulatory mechanisms of neuronal death in CI settings...

Sirtuin 1 (SIRT1), an NAD+ -dependent deacetylase, is a crucial regulator that produces multiple physiological benefits, such as the prevention of cancer and age-related diseases. SIRT1 is activated by sirtuin-activating compounds (STACs). Here, we report that quercetin 3,5,7,3',4'-pentamethyl ether (KPMF-8), a natural STAC from Thai black ginger Kaempferia parviflora, interacts with SIRT1 directly and stimulates SIRT1 activity by enhancing the binding affinity of SIRT1 with Ac-p53 peptide, a native substrate peptide without a fluorogenic moiety...

Stress resistance correlates with longevity and this pattern has been exploited to help identify genes that can influence lifespan. Reciprocally, genes and pharmacological agents that have been studied primarily in the context of longevity may be an untapped resource for treating acute stresses. Here we summarize the evidence that targeting SIRT1, studied primarily in the context of longevity, can improve outcomes in hemorrhagic shock and resuscitation. Hemorrhagic shock is a potentially fatal condition that occurs when blood loss is so severe that tissues no longer receive adequate oxygen...

Caloric restriction (CR) has been shown repeatedly to prolong the lifespan in laboratory animals, with its benefits dependent on molecular targets forming part of the nutrient signaling network, including the NAD-dependent deacetylase silent mating type information regulation 2 homologue 1 (SIRT1). It has been hypothesized that the stilbene resveratrol (RSV) may counteract age- and obesity-related diseases similarly to CR. In yeast and worms, RSV-promoted longevity also depended on SIRT1. While it remains unclear whether RSV can prolong lifespans in mammals, some studies in rodents supplemented with RSV have reported lowered body weight (BW) and fat mass, improved insulin sensitivity, lowered cholesterol levels, increased fitness, and mitochondrial biogenesis...

Unlike widely perceived, resveratrol (RSV) decreased the average lifespan and extended only the replicative lifespan in yeast. Similarly, although not widely discussed, RSV is also known to evoke neurite degeneration, kidney toxicity, atherosclerosis, premature senescence, and genotoxicity through yet unknown mechanisms. Nevertheless, in vivo animal models of diseases and human clinical trials demonstrate inconsistent protective and beneficial effects. Therefore, the mechanism of action of RSV that elicits beneficial effects remains an enigma...

BACKGROUND AND PURPOSE: Vasospasm and delayed cerebral ischemia (DCI) contribute significantly to the morbidity/mortality associated with aneurysmal subarachnoid hemorrhage (SAH). While considerable research effort has focused on preventing or reversing vasospasm, SAH-induced brain injury occurs in response to a multitude of concomitantly acting pathophysiologic mechanisms. In this regard, the pleiotropic epigenetic responses to conditioning-based therapeutics may provide an ideal SAH therapeutic strategy...

Sirtuins are class III histone deacetylases, whose enzymatic activity is dependent on NAD+ as a cofactor. Sirtuins are reported to modulate numerous activities by controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis. Deregulation of their expression and/or action may lead to tissue-specific degenerative events involved in the development of several human pathologies, including cancer, neurodegeneration, and cardiovascular disease. The most studied member of this class of enzymes is sirtuin 1 (SIRT1), whose expression is associated with increasing insulin sensitivity...