Specifically, fisetin enhanced the association between SIRT1 and the PPAR promoter, leading to a block of its transcriptional activity, adipogenesis, and lipid accumulation (Kim et al., 2015). Resveratrol protects H9c2 cells against hypoxia-induced apoptosis through miR-30d-5p/SIRT1/NF-kappaB axis. DoNotAge has chosen to market fucoidan from. 95, 12251231. showed that fisetin mediated protective effects via SIRT1 activation, enhancing NF-B deacetylation and promoting inhibition of pro-inflammatory gene expression (Singh et al., 2019). Due to its poor solubility, short half-life, and low bioavailability, its medical use is limited (Konrad and Nieman, 2015). Quercetin improve ischemia/reperfusion-induced cardiomyocyte apoptosis in vitro and in vivo study via SIRT1/PGC-1alpha signaling. A list of clinical studies investigating the beneficial effects of BBR in inflammatory and metabolic diseases is reported in Table 4. 118 (12), 43494357. At low concentrations (1010 M), Que displayed a protective effect against oxidative DNA damage (in vitro) in human lymphocytes (Li et al., 2016). Resveratrol (RSV), a non-flavonoid polyphenol found in grapes and grape products such as red wine, exerts an antioxidant action with reported cancer preventive properties (Kris-Etherton et al., 2002). Recent research showed that oxidized LDL (oxLDL) induces oxidative stress (Lara-Guzman et al., 2018). Initial research revealed a significant role of SIRT1 signaling in mediating the antioxidant effect of BBR in diabetes (Pang et al., 2015) and in lipid metabolism (Hasanein et al., 2017). 109, 21362144. doi:10.1007/s13105-016-0492-6, Lara-Guzman, O. J., Gil-Izquierdo, A., Medina, S., Osorio, E., Alvarez-Quintero, R., Zuluaga, N., et al. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. (2002). 73, 7183. doi:10.1016/j.mrrev.2011.11.001, Price, N. L., Gomes, A. P., Ling, A. J., Duarte, F. V., Martin-Montalvo, A., North, B. J., et al. BPA and Nutraceuticals, Simultaneous Effects on Endocrine Functions. 58 (10), 13091317. Quercetin Isolated from Toona sinensis Leaves Attenuates Hyperglycemia and Protects Hepatocytes in High-Carbohydrate/High-Fat Diet and Alloxan Induced Experimental Diabetic Mice. Resveratrol mitigates lipopolysaccharide- and Abeta-mediated microglial inflammation by inhibiting the TLR4/NF-kappaB/STAT signaling cascade. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. (2020). RSV has an effect on blood vessels, reduces inflammation, and prevents thrombus formation and platelet oxidation (Zordoky et al., 2015). Clin. 2 (3), 218229. However, Que was also found to have potentially toxic effects including mutagenicity, pro-oxidant activity, mitochondrial toxicity, and inhibition of enzymes involved in hormonal metabolism (Li et al., 2016). (2018). (2016). FoxO proteins and cardiac pathology. Most of the evidence supporting the beneficial effects of phytochemical compounds comes from in vitro or animal studies, while human studies evaluating the long-term impact of phytomolecules are particularly few or inconsistent. Through NF-B, SIRT1 also regulates the expression of genes such as inhibitor of apoptosis protein (IAP) and B-cell lymphoma-2 (Bcl-2) and tumor necrosis factor receptor (TNFR) (Ren et al., 2019). Cur may have positive effects in T2D by mediating the reduction of NF-B expression in inflammatory pathway (Zendedel et al., 2018). (2020a). Curcumin (Cur) or 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (diferuloylmethane) is a natural bioactive polyphenol compound mediating a wide spectrum of biological functions. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes control the levels of histone acetylation, modulating gene expression (Cavalli and Heard, 2019). 113 Suppl 9B, 71S88S. 2016:1689602. doi:10.1155/2016/1689602, Yu, Y., Sun, J., Wang, R., Liu, J., Wang, P., Wang, C. (2019). Interv. Bioactive compounds in the diet can act as antioxidant and anti-inflammatory agents, thereby reducing the negative effects of oxidative stress and the incidence of chronic diseases such as obesity, diabetes, and cardiovascular disorders (Wang et al., 2014). 3 (4), 437441. Antagonistic crosstalk between NF-kappaB and SIRT1 in the regulation of inflammation and metabolic disorders. Anti-inflammatory effects of resveratrol and its potential use in therapy of immune-mediated diseases. Sci. The effect of resveratrol on hypertension: A clinical trial. At concentrations between 5 M and 50 M, Que was able to directly eliminate ROS in vitro (Costa et al., 2016). Nrf2 is a transcription factor involved in cellular stress response. SIRT1 is also able to regulate the expression of superoxide dismutase (SOD) and glutathione peroxidase (Sun et al., 2018). If none of them activate SIRT6 then we start again. 72 (3), 371380. doi:10.1016/j.bbrc.2015.10.094, Konrad, M., Nieman, D. C. (2015). 13 (1), 295301. Furthermore, activation of SIRT1/PGC-1 pathway upregulated Bcl-2 expression and downregulated Bax, exerting anti-apoptotic effects. Sirtuins (SIRT) 17 are enzymes classified as class III HDACs. Fisetin was shown to have neuroprotective activity in various Huntingtons disease models through ERK activation and to inhibit melanoma growth by suppressing Akt/mTOR1 pathway (Sechi et al., 2018). doi:10.1159/000493650, Ma, X., Sun, Z., Han, X., Li, S., Jiang, X., Chen, S., et al. Many clinical studies conducted in healthy patients and volunteers using both high and low doses of RSV highlight its potential cardioprotective benefit through improvement of endothelial function, inflammatory markers, and glucose metabolism. Food Res. Restricting the search to interventional phase 1/2/3/4 studies (completed and terminated clinical trials), 55 addressed the ability of RSV to improve the pathological conditions of patients affected by several diseases. The growing body of evidence supporting the beneficial effects of Que has led to its clinical use, as demonstrated by the number of clinical trials (72 studies on ClinicalTrials.gov). Biol. Front. By modulating the acetylation level of NF-B p65, SIRT1 is able to control transcription of genes such as IL (interleukin)-1, tumor necrosis factor (TNF-), IL-8, IL-6, and other inflammatory factors (Rodgers et al., 2005; Ren et al., 2019; Yeung et al., 2019). Adv. A., Lertpiriyapong, K., Steelman, L. S., Abrams, S. L., Yang, L. V., Murata, R. M., et al. Patients were subjected to five different Cur doses (500, 1,000, 2,000, 4,000, and 8,000 mg) every day for 3 months, and data showed that Cur treatment up to 8,000 mg/day is not toxic (Hsu and Cheng, 2007). Med. 750 (1), 6082. Biol. (2018). Protective effect of quercetin against sodium fluoride induced oxidative stress in rats heart. showed an increase in AMPK phosphorylation and SIRT1 expression levels, while in vitro results revealed a reduction in lipid accumulation and an increase in lipolysis. RSV was shown to be involved in the activation of macrophages, T cells, and natural killer cells, as well as in the suppression processes of CD4+ CD25+ regulatory T cells (Yang et al., 2008; Svajger and Jeras, 2012). Endocrinol. (2017). Redox Signal 18 (14), 18181892. 6 (1), 287296. doi:10.12659/MSM.911714, Zhu, X., Yang, J., Zhu, W., Yin, X., Yang, B., Wei, Y., et al. B. Clinical studies with curcumin. Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte. Biofactors 46 (1), 168179. Rep. 8 (1), 15726. doi:10.1038/s41598-018-33879-w, Serafini, M. M., Catanzaro, M., Fagiani, F., Simoni, E., Caporaso, R., Dacrema, M., et al. J. Nutr. doi:10.1038/nature03354, Romagnolo, D. F., Selmin, O. I. Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells. Br. 119 (12), 1029110300. doi:10.1007/978-0-387-46401-5_21, Hsu, C. P., Zhai, P., Yamamoto, T., Maejima, Y., Matsushima, S., Hariharan, N., et al. Que may reduce infection (Li et al., 2016), hepatic lipemic-oxidative damage (Cui et al., 2013) (Zhang et al., 2016b), and antioxidant risk (Xu et al., 2019). (2004). Med. Lipid accumulation is a common feature in NAFLD (Liou et al., 2018). Cell Longev. (2017). Nutr. In contrast, under stress conditions Keap1 activity is inhibited by phosphorylation and free Nrf2 moves to the nucleus, where it binds to ARE in the regulatory regions of cytoprotective proteins and promotes transcription of antioxidant genes such as SOD, glutathione peroxidase (GPx), and GSH, and of phase II detoxifying enzymes such as heme oxygenase-1 (HO-1), glutathione transferases (GST), nicotinamide adenine dinucleotide phosphate (NADPH), and NAD(P)H dehydrogenase [quinone] 1 (NQO1) (Serafini et al., 2019). doi:10.1007/s11064-018-2597-5, Hung, C. H., Chan, S. H., Chu, P. M., Tsai, K. L. (2015). doi:10.5483/bmbrep.2013.46.4.033, Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M. T., Wang, S., et al. Fisetin was shown to increase SIRT1 expression and enhance SIRT1-mediated PPAR and FOXO1 deacetylation in 3T3L1 cells (Kim et al., 2015). Today 52 (5), 208222. The molecular structure of Cur consists of two aromatic rings containing phenolic O-methoxy groups linked by a carbon bond, which has a -unsaturated -diketone fraction (Priyadarsini, 2014). Front. Lett. Commun. Annu. Exp. Neurochem. So countries with the highest consumption of seaweed are Japan and South Korea; people in these countries have the highest life expectancy and they eat a lot of seaweed, so weve been screening different preparations of seaweed and fucoidan and we have identified those that are really strong inducers of sirtuin 6 activity. SOCS is an antagonist of JAK/STAT signaling and is involved in the regulation of inflammatory proteins and cytokines. Neurosci. Toxicol. All these effects are due to its ability to remove ROS, inhibit cyclooxygenase (COX), and trigger anti-inflammatory pathways via SIRT1 activation (Miceli et al., 2014; Malaguarnera, 2019). doi:10.2337/db16-0153, Yamagata, K. (2019). Table 2 Resveratrol in clinical trials for metabolic disorders. This effect did not occur if H9c2 cells were treated with the SIRT1 inhibitor EX-527 (Bai et al., 2018), indicating that BBR action was dependent on SIRT1 (Wu et al., 2019). Med. (2017). Lett. Data obtained in diabetic mice models showed that supplementation of Cur for 8 weeks might promote indirect activation of SIRT1 through AMPK (Jimenez-Flores et al., 2014). doi:10.1016/j.archoralbio.2013.07.005, Gupta, S. C., Patchva, S., Koh, W., Aggarwal, B. doi:10.1038/onc.2017.296, Sampaio, S. F., Branco, A. F., Wojtala, A., Vega-Naredo, I., Wieckowski, M. R., Oliveira, P. J. doi:10.1111/j.1471-4159.2011.07594.x, Cavalli, G., Heard, E. (2019). Arch. Biochem. However, as for RSV and nutraceuticals in general, the results of molecular studies on Que obtained from in vitro investigations and animal models are often inconsistent with data from clinical trials. Mediterranean diets are in fact linked to a reduced risk of chronic diseases due to the consumption of olive oil and red wine, which contain high amounts of polyphenols (Romagnolo and Selmin, 2017). Antioxid. doi:10.1126/science.1094637, Capiralla, H., Vingtdeux, V., Zhao, H., Sankowski, R., Al-Abed, Y., Davies, P., et al. doi:10.1016/j.brainresbull.2016.02.011, Wang, S., Moustaid-Moussa, N., Chen, L., Mo, H., Shastri, A., Su, R., et al. Maternal quercetin administration during gestation and lactation decrease endoplasmic reticulum stress and related inflammation in the adult offspring of obese female rats. doi:10.1210/jc.2010-0482, Gu, X., Han, D., Chen, W., Zhang, L., Lin, Q., Gao, J., et al. SIRT1-mediated FoxOs pathways protect against apoptosis by promoting autophagy in osteoblast-like MC3T3-E1 cells exposed to sodium fluoride. To date, 165 clinical trials have tested the efficacy, safety, and pharmacokinetics of RSV in the prevention and treatment of 32 different pathological conditions (www.clinical.trials.gov). doi:10.1016/s0002-9343(01)00995-0, Kupis, W., Palyga, J., Tomal, E., Niewiadomska, E. (2016). Rev. 106 (3), 383389. doi:10.1002/jcb.27371, Zhang, X., Wu, J., Ye, B., Wang, Q., Xie, X., Shen, H. (2016a). (2020b). doi:10.1016/j.biopha.2018.11.064, PubMed Abstract | CrossRef Full Text | Google Scholar, Araki, T., Sasaki, Y., Milbrandt, J. Endocr. Protective effect of resveratrol against pressure overload-induced heart failure. 25 (22), 24432458. Overall, these findings suggest that Que may counteract cardiovascular disease and oxidative damage. (2016). J. Neurochem. doi:10.1007/978-3-319-41342-6_17, OCallaghan, C., Vassilopoulos, A. Biol. Oncogene 36 (50), 69066918. doi:10.1023/B:JOCI.0000040925.55682.a5, Nabavi, S. F., Nabavi, S. M., Mirzaei, M., Moghaddam, A. H. (2012). (2017). Indeed, SIRT1 has been reported to play a key role in tumorigenesis, as an oncogene or tumor suppressor depending on the context specificity (Biason-Lauber et al., 2013). 25 (3), 138145. The administration of 2g of Que led to a decrease in postprandial blood glucose (NCT01839344). 17 (3), 448455. Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving SIRT1 and PGC-1alpha. Biol. A further question is related to the cell/context-specific expression of some SIRTs, cofactor availability, and context-specific action of some of the described modulators. (2016). doi:10.3390/molecules19010291, de Boer, V. C., de Goffau, M. C., Arts, I. C., Hollman, P. C., Keijer, J. Food Res. Curcumin abrogates LPS-induced pro-inflammatory cytokines in RAW 264.7 macrophages. However, its all worth it for the end result genomic stability, reduced inflammation, DNA repair, and ultimately wed like to see a great increase in health and lifespan. doi:10.1089/ars.2012.4581, Donniacuo, M., Urbanek, K., Nebbioso, A., Sodano, L., Gallo, L., Altucci, L., et al. Table 6 Fisetin in clinical trials for inflammatory disorders. J. Appl. Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration. Pharmacol. Today, Cur is considered a potential agent with antioxidant, anticancer, and anti-inflammatory properties (Yu et al., 2019). Cardioprotective effect of a moderate and prolonged exercise training involves sirtuin pathway. Res. Quercetin, Inflammation and Immunity. 13, 97107. Front. 81 (1 Suppl), 268S276S. Berberine attenuated the cytotoxicity induced by t-BHP via inhibiting oxidative stress and mitochondria dysfunction in PC-12 cells. Immunol. (2016). 929, 377387. They are found in many plants and foods, such as fruits, vegetables, tea, cereals, and wine, and long-term intake is associated with health benefits. 80 (2), 6273. (2015). SIRT6 is a protein with an important job; it is vital for both normal base excision repair and double-strand break repair of DNA damage, as this damage leads to genomic instability, ultimately contributing to aging. A recent study investigated the neuroprotective effects of fisetin as a possible CRM against apoptosis, oxidative stress, aging, and neurodegeneration (Singh et al., 2018). However, some studies highlighted the potential ability of BBR to prevent oxidative stress-induced senescence by activating AMPK and restoring NAD+ levels (Song et al., 2020). Am. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Biophys. Antioxidants: Scientific Literature Landscape Analysis. J. Biosci. These pilot studies aim to test the anti-inflammatory efficacy of fisetin in Frail Elderly Syndrome (NCT03675724 and NCT03430037) and in symptomatic knee osteoarthritis patients (NCT04210986). Yang and colleagues investigated SIRT1 action after Cur treatment and the manner in which Cur might attenuate MI/R-induced mitochondrial oxidative damage. Abdelsamia, E. M., Khaleel, S. A., Balah, A., Abdel Baky, N. A. This human diet constituent is reported to exert some beneficial anticancer, cardiovascular preventive, anti-inflammatory, and antioxidant effects that support normal cell homeostasis and cytoprotection (Chen et al., 2015; Kim et al., 2015). A pilot study of the antioxidant effect of curcumin in tropical pancreatitis. The flavonoid polyphenol quercetin (Que; 3,3,4,5,7-pentahydroxyflavone) is a natural, safe dietary supplement found in a glycoside form in fruits, vegetables, and nuts, which has antioxidant and anti-inflammatory properties (Nabavi et al., 2012; Wu et al., 2014). Que is a powerful ROS scavenger and its antioxidant action is due to the presence of two pharmacophores within the molecular structure, which confer a favorable configuration for free radical elimination (Costa et al., 2016). J. Nutr. Furthermore, BBR can inhibit colon cancer cell growth by activating retinoid X receptor (RXR), which binds RXR, and promoting -catenin degradation (Ruan et al., 2017). A., Kim, C. W. (2008). (2006). (2012). SIRT1 has been implicated in both tumorigenic and anticancer processes, and is reported to regulate essential metabolic pathways, suggesting that its activation might be beneficial against disorders of the metabolism. BBR attenuated oxidative stress by increasing SOD1 levels through activation of SIRT1 and inhibition of miR-106b expression (Chen and Yang, 2017). Diabetol. doi:10.1016/j.cellsig.2013.06.007, Khan, N., Syed, D. N., Ahmad, N., Mukhtar, H. (2013). Redox Rep. 22 (1), 4250. Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1. Mutat. Commun. Regulation of SIRT1 by oxidative stress-responsive miRNAs and a systematic approach to identify its role in the endothelium. doi:10.1089/ars.2012.4803, Chen, P. Y., Ho, Y. R., Wu, M. J., Huang, S. P., Chen, P. K., Tai, M. H., et al. Aging (Albany NY) 9 (6), 14771536. Our current knowledge of the potential pharmacological activation of the expression/activity of other SIRTs is largely incomplete. (2018). Sci. SIRT1 activated by RSV inhibits acetylation of RelA by reducing the expression of inflammatory factors such as TNF-, IL-1, IL-6, metalloprotease (MMP)-1, MMP-3, and NF-B-mediated Cox-2 (Malaguarnera, 2019). Specifically, a phase 2 clinical trial (NCT01839344) measured the effect of Que on glucose tolerance and postprandial endothelial function in subjects with T2D compared to the effect of an alpha-glusidase inhibitor, acarbose. Modulation of Keap1/Nrf2/ARE Signaling Pathway by Curcuma- and Garlic-Derived Hybrids. 2019:2150394. doi:10.1155/2019/2150394, Xu, D., Hu, M. J., Wang, Y. Q., Cui, Y. L. (2019). Cell Biochem. Med. doi:10.2147/JIR.S232009, Ghanim, H., Sia, C. L., Abuaysheh, S., Korzeniewski, K., Patnaik, P., Marumganti, A., et al. The enzymatic activity of SIRTs is dependent on NAD+ as a cofactor and plays an important role in controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis. Natural substances have beneficial effects on human health by regulating SIRT1 action in different cellular processes (www.pubchem.ncbi.nlm.nih.gov). Biological activity of piceatannol: leaving the shadow of resveratrol. Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3beta Activity. In vascular smooth muscle cells, Cur promotes AMPK activation, which enhances superoxide and ATP production. FIRST LONGEVITY, increasing life expectancy in mice by 30%, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614943/, https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.318353, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389893/, https://www.cell.com/cell/fulltext/S0092-8674(19)30344-7, https://www.sciencedirect.com/science/article/pii/S2213453019300254, https://www.researchgate.net/publication/317755025_The_Identification_of_a_SIRT6_Activator_from_Brown_Algae_Fucus_distichus, The weight loss supplement that boosts the benefits of exercise, From movement to industry a longevity journey, HIV speeds up bodys aging processes, new study shows, Study disproves benefits of probiotics for vaginal health, Cinnamon a little compound which could slow diabetes, New supplement slows aging and promotes weight loss, FuturSelf a new digital approach to mental health, Research reverses aging in human skin cells by 30 years, YouthBio CEO: The time is right to develop epigenetic reprogramming therapies, Andrew Steele: Our goal must be to cure aging, Dr Frank Lipman explains how supplementing with NMN can help boost cellular energy, New research shows urolithin A improves mitochondrial health and reduces joint cartilage damage, GLYLO the weight loss supplement that boosts the benefits of exercise, Supplement trials go step-by-step for success, Winning strategy Tour de France riders supplement with urolithin A, Senostatic study shows admirable results for longevity supplement, Studies show NOVOS ingredient combo maintains DNA and targets senescence, Longevity startup Avea closes CHF 2.5 million in first financing round, Elevants longevity routine aims to improve your health and help you live better for longer, Wonderfeel launch Youngr a new supplement targeting the root causes of aging, A new longevity supplement that speaks for itsCELLF, Science breakthrough shows the way to faster muscle recovery, New immune supplement launches with NAD+ boost for optimal maintenance of aging cells, New gluten-free, soy-free spermidine supplement launches, Swiss scientists crack muscle recovery, repairing age-related fatigue. BioMed. Que may reduce oxLDL-induced oxidative damage by upregulating SIRT1 and AMPK (Hung et al., 2015), therefore potentially preventing oxLDL-impaired SIRT1 inhibition linked to endothelial dysfunction. 24, 36. doi:10.1186/s11658-019-0158-9, Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., Puigserver, P. (2005). Biochem. Tang and colleagues evaluated the effects of Que in improving myocardial ischemia/reperfusion injury (MI/R)-induced cell apoptosis both in vitro and in vivo.
Daich Coatings For Concrete, Body Butter Manufacturers, Essie Apricot Nail & Cuticle Oil, Hayward Sp1091lx Dimensions, What Underlay For Artificial Grass, 1/4 Inch Barbed Connector, Minc Foil Transfer Machine,