Nutrients 8 (3):167. doi:10.3390

Nutrients 8 (3):167. doi:10.3390/nu8030167, Li, L., Wang, X., Sharvan, R., Gao, J., Qu, S. (2017). J. Physiol.

Med. BMC Complement Altern. SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury.

Cur may have positive effects in T2D by mediating the reduction of NF-B expression in inflammatory pathway (Zendedel et al., 2018). SOCS is an antagonist of JAK/STAT signaling and is involved in the regulation of inflammatory proteins and cytokines.

Pathol. As well as activating SIRT1, BBR is also able to decrease FOXO1 acetylation, triggering anti-apoptotic signaling pathways via Bcl-2 expression, and Bax and caspase-3 downregulation (Yu et al., 2016). Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases.

Rev. Cell Biochem. doi:10.1039/c2fo10264a, Nair, M. P., Kandaswami, C., Mahajan, S., Chadha, K. C., Chawda, R., Nair, H., et al. 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). doi:10.1016/j.jnutbio.2013.09.001, Wong, A., Woodcock, E. A. doi:10.1161/CIRCULATIONAHA.110.958033, Hu, T., Shi, J. J., Fang, J., Wang, Q., Chen, Y. Over the past few years, the ever-growing awareness that good health goes hand in hand with a healthy and balanced diet has encouraged people to eat more fruit and vegetables, and to take supplements to make up for any deficiency (DAngelo et al., 2019). Another study investigated Cur-mediated effects in patients with chronic non-alcoholic pancreatitis, showing that patients had a strong reversal of lipid peroxidation (Durgaprasad et al., 2005). doi:10.1016/j.mad.2006.02.007, Del Rio, D., Rodriguez-Mateos, A., Spencer, J. P., Tognolini, M., Borges, G., Crozier, A. Biophys.

In vascular smooth muscle cells, Cur promotes AMPK activation, which enhances superoxide and ATP production. 95 (9), E1E8. After we showed that not all harvests of this ingredient activate Sirtuin 6, we set about finding those that did. Med. Cell Signal 25 (10), 19391948. The beneficial effects of fisetin were also linked to its action as a caloric restriction mimetic (CRM) (Singh et al., 2018). Monit. Biological properties and clinical applications of berberine. SIRT1 also regulates inflammatory response (Kauppinen et al., 2013). Med. (2017). Neurobiol. The flavonoid, quercetin, differentially regulates Th-1 (IFNgamma) and Th-2 (IL4) cytokine gene expression by normal peripheral blood mononuclear cells.

Substantial amounts of the compounds and their metabolites are degraded in the colon by intestinal microbiota, giving rise to small phenolic acids and aromatic catabolises which are absorbed by the circulatory system (Del Rio et al., 2013). doi:10.1210/jc.2010-0482, Gu, X., Han, D., Chen, W., Zhang, L., Lin, Q., Gao, J., et al. 95, 12251231. Cell Longev. Resveratrol, Metabolic Syndrome, and Gut Microbiota. (2010). Fisetin, a potential caloric restriction mimetic, modulates ionic homeostasis in senescence induced and naturally aged rats. Because of the pleiotropic actions of RSV, clinical trials are currently testing its therapeutic potential in a wide range of human diseases. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. A., Kim, C. W. (2008). Aging Cell 16 (6), 12081218. A very recent report described the protective effect of BBR against doxorubicin-induced cardiovascular damage (Wu et al., 2019). Drug Targets 19 (5), 594604. N-n-Butyl Haloperidol Iodide, a Derivative of the Anti-psychotic Haloperidol, Antagonizes Hypoxia/Reoxygenation Injury by Inhibiting an Egr-1/ROS Positive Feedback Loop in H9c2 Cells. Science 305 (5686), 10101013. doi:10.1017/S0007114511000316, Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., et al. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. (2013). Food Res. Med. (2013). (2012). doi:10.1002/biof.1584, Li, Z., Jiang, T., Lu, Q., Xu, K., He, J., Xie, L., et al. 277, 115122. 10:1597:1597. doi:10.3389/fphar.2019.01597, Shanmugam, K., Ravindran, S., Kurian, G. A., Rajesh, M. (2018). Life Sci. 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). Mitochondrial Dynamic Dysfunction as a Main Triggering Factor for Inflammation Associated Chronic Non-Communicable Diseases. doi:10.18632/oncotarget.11573, Guimaraes, M. R., Leite, F. R., Spolidorio, L. C., Kirkwood, K. L., Rossa, C., Jr. (2013). (2006). Exp. Specifically, BBR and RSV co-treatment was able to reduce lipid accumulation more robustly than single treatments.

Exp. doi:10.1007/s11064-018-2597-5, Hung, C. H., Chan, S. H., Chu, P. M., Tsai, K. L. (2015). A recent study investigated the neuroprotective effects of fisetin as a possible CRM against apoptosis, oxidative stress, aging, and neurodegeneration (Singh et al., 2018).

40 (4), 587602. doi:10.1007/978-1-4419-1599-3_6, Wu, Z., Zhao, J., Xu, H., Lyv, Y., Feng, X., Fang, Y., et al. However, its effect in vivo is very likely not direct but due to its ability to modulate the cells antioxidant defense mechanisms; moderate oxidative stress can in fact increase the cells antioxidant defenses, resulting in general cytoprotection (Halliwell et al., 2005). New SIRT6 activator supplement hits the market, Copyright 2022 FIRST LONGEVITY Limited. 127 (7), 618627. Physiol. (2016b). Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF: Nrf2 and antioxidant mechanisms in skeletal muscle. Molecules 19 (1), 291305. Protective effect of curcumin on TNBS-induced intestinal inflammation is mediated through the JAK/STAT pathway. 61, 4855. Sirtuins are reported to modulate numerous activities by controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis.

Despite clinical evidence of its effects, the poor bioavailability and rapid metabolism of RSV severely limit the potential use of this molecule in the clinic. Future scientific research should focus on identifying actual metabolites or mediators of these observed effects. (2016). Med. (2005).

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. Concentration factor (dose and timing of administration) and bioavailability are the two main issues that require further clarification. These effects were abolished when cardiomyocytes were treated with SIRT1 siRNA. Protective effects of quercetin and quercetin-5,8-disulfonate against carbon tetrachloride-caused oxidative liver injury in mice. Endocrinol. Nutr. Lipid accumulation is a common feature in NAFLD (Liou et al., 2018). Improved Glycemic Control and Vascular Function in Overweight and Obese Subjects by Glyoxalase 1 Inducer Formulation. SIRT1 protects against oxidative stress via regulation of FOXO protein acetylation, which is involved in antioxidant processes, apoptosis, and cell proliferation (Wong and Woodcock, 2009). Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More. Quercetin and Its Role in Chronic Diseases. (2013). This review will examine compounds of natural origin recently found to upregulate SIRT1 activity, such as polyphenolic products in fruits, vegetables, and plants including resveratrol, fisetin, quercetin, and curcumin.

SIRT1 and PGC-1 expression levels were decreased in rat MI/R groups, but were significantly increased after treatment with Que (Tang et al., 2019). 90 (7), 16691684. (2018). 90, 500508. Metab. doi:10.1007/s00204-005-0014-8, Ingram, D. K., Zhu, M., Mamczarz, J., Zou, S., Lane, M. A., Roth, G. S., et al. doi:10.1080/13813455.2019.1662452, Song, D., Hao, J., Fan, D. (2020).

doi:10.2147/CIA.S158513, Liou, C. J., Wei, C. H., Chen, Y. L., Cheng, C. Y., Wang, C. L., Huang, W. C. (2018). At low concentrations (1010 M), Que displayed a protective effect against oxidative DNA damage (in vitro) in human lymphocytes (Li et al., 2016).

doi:10.1080/13510002.2016.1140406, Hsu, C. H., Cheng, A. L. (2007). Redox Signal 19 (13), 15221538. 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. It can also reduce cardiac dysfunction, oxidative stress, fibrosis, and apoptosis in the heart (Gupta et al., 2014; Yamagata, 2019). Resveratrol provides neuroprotection by inhibiting phosphodiesterases and regulating the cAMP/AMPK/SIRT1 pathway after stroke in rats. (2004). doi:10.12659/MSM.911714, Zhu, X., Yang, J., Zhu, W., Yin, X., Yang, B., Wei, Y., et al. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Two other trials, a phase 2 (NCT02017353) and a phase 3 (NCT02099890) study, investigated the effect of Cur on inflammation induced by endometrial carcinoma and spinal cord injury, respectively.

39 (3), 283299. Sechi, M., Lall, R. K., Afolabi, S. O., Singh, A., Joshi, D. C., Chiu, S. Y., et al. (2016). 929, 377387. doi:10.1016/j.bbrc.2015.10.094, Konrad, M., Nieman, D. C. (2015). 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. Resveratrol Reduces Oxidative Stress and Apoptosis in Podocytes via Sir2-Related Enzymes, Sirtuins1 (SIRT1)/Peroxisome Proliferator-Activated Receptor gamma Co-Activator 1alpha (PGC-1alpha) Axis. SIRT6Activator is a natural product derived from a strain of seaweed is called Fucus Vesiculosus. Several molecules, including natural phytochemical compounds, can modulate SIRT1 activity (Miceli et al., 2014). 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).

Ed.

Durgaprasad, S., Pai, C. G., Vasanthkumar, Alvres, J. F., Namitha, S. (2005). However, the sea is cruel mistress, and the majority of Fucus Vesiculosus tested by DoNotAge had the opposite effect to the one they wanted and actually inhibited SIRT6. The involvement of mitochondrial oxidative damage in several diseases such as MI/R is well known (Yang et al., 2013). Endocr. In oral carcinoma cell lines and in SCC-4 cells, BBR inhibits expression of COX2 and AP-1 bond, decreases prostaglandin E2 (PGE2) production, and suppresses NF-B, IKK, ERK, and JNK activities. Pharmacol. 72 (3), 371380. Cell Mol.

doi:10.1016/j.clnu.2019.06.026, Miceli, M., Bontempo, P., Nebbioso, A., Altucci, L. (2014). 222, 140147. Silent information regulator 1 protects the heart from ischemia/reperfusion. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) enzymes control the levels of histone acetylation, modulating gene expression (Cavalli and Heard, 2019). Curcumin Management of Myocardial Fibrosis and its Mechanisms of Action: A Review. 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. M. Lamprecht (Boca Raton, FL: CRC Press/Taylor & Francis), Kris-Etherton, P. M., Hecker, K. D., Bonanome, A., Coval, S. M., Binkoski, A. E., Hilpert, K. F., et al.

Oncotarget 7 (40), 6521865230. 24 (5), 542552. Quercetin-Induced miR-369-3p Suppresses Chronic Inflammatory Response Targeting C/EBP-beta. Identification of a SIRT1 mutation in a family with type 1 diabetes. Numerous studies investigated the beneficial effects of RSV in cardiovascular diseases including hypertension (Theodotou et al., 2017), cardiac ischemia (Fourny et al., 2019), and atherosclerosis (Chassot et al., 2018). Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Biophys. 2019:8278454. doi:10.1155/2019/8278454, Yu, L., Li, Q., Yu, B., Yang, Y., Jin, Z., Duan, W., et al. 13:1400:1400. doi:10.3389/fnins.2019.01400, Malaguarnera, L. (2019). In different organisms (S. cerevisiae, C. elegans, and D. melanogaster) expressing SIRT1 (or its homologous genes), RSV treatment is able to extend life span.

750 (1), 6082. doi:10.1002/fsn3.92, Haigis, M. C., Sinclair, D. A. (2019). BBR-mediated SIRT1 activation reduced MI/R injury by affecting oxidative damage and inflammation signaling. In these conditions, the levels of decreased SIRT1 abolished the effects of Cur treatment. BBR was described as a potential antitumor agent that induces cell cycle arrest in G0/G1 phase, increases Cip/p21 and Kip/p27 protein expression, decreases expression of cyclin D1, D2, and DE, and the cyclin-dependent kinases Cdk2, Cdk4, and Cdk6, promoting apoptosis in HL-60 human leukemia cells (Li et al., 2017). doi:10.3109/08830185.2012.665108, Tang, J., Lu, L., Liu, Y., Ma, J., Yang, L., Li, L., et al. 12 (2), 159162. 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). (2012). doi:10.1111/j.1474-9726.2006.00202.x, Iskender, H., Dokumacioglu, E., Sen, T. M., Ince, I., Kanbay, Y., Saral, S. (2017).

SIRT1, Sirtuin 1; HATs, Histone acetyl transferases; HDACs, Histone deacetylases; ROS, Reactive oxygen species; PPAR, Receptor peroxisome proliferator-activated receptor; NRF, Nuclear respiratory factor; TFAM, Mitochondrial transcription factor A; SOD, Superoxide dismutase; TNF-, Tumor necrosis factor ; IAP, Apoptosis protein inhibitor; Bcl-2, B-cell lymphoma-2 family; MnSOD, Manganese superoxide dismutase; RSV, Resveratrol; Que, Quercetin; oxLDL, Oxidized LDL; BBR, Berberine; Cur, Curcumin; COX, Cytochrome c oxidase; T2D, Type II diabetes; NAFLD, Non-alcoholic fatty liver disease; CRM, Caloric restriction mimetic. doi:10.1146/annurev.pathol.4.110807.092250, Halliwell, B., Rafter, J., Jenner, A. Moreover, BBR pre-treatment seemed to counteract SIRT1 downregulation (Zhu et al., 2018).

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). Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/NF-kappaB-induced inflammatory mediators production in RAW 264.7 cells. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Many of them even inhibit Sirtuin 6, which is why we had to protect the ingredient Its laborious, complex and painful to produce, which means supply is limited. (2013). BioMed. doi:10.1016/j.freeradbiomed.2013.07.007, Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., et al. (2002). All rights reserved. 23 (12), 23692380. Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages. It was very recently shown that Que (70 mg/kg) can reduce insulin resistance and improve glucose metabolism by reducing sensitivity to T2D/insulin resistance in ob/ob mice via SIRT1 activation (Hu et al., 2020). Acta 1593 (1), 2936. Natural compounds in epigenetics: a current view. Regulation of SIRT1 by oxidative stress-responsive miRNAs and a systematic approach to identify its role in the endothelium. (2013). doi:10.1016/j.jnutbio.2018.07.014, Cheang, W. S., Wong, W. T., Wang, L., Cheng, C. K., Lau, C. W., Ma, R. C. W., et al. Overall, these findings suggest that Que may counteract cardiovascular disease and oxidative damage. (2006). Food Chem. 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). doi:10.3892/etm.2016.3958, Tian, X. Y., Wong, W. T., Wang, N., Lu, Y., Cheang, W. S., Liu, J., et al. The most studied member of this class of enzymes is sirtuin 1 (SIRT1), whose expression is associated with increasing insulin sensitivity. Cytoprotective effects of fisetin against hypoxia-induced cell death in PC12 cells. (2015). J. Nutr. Sci. No use, distribution or reproduction is permitted which does not comply with these terms. Berberine (BBR) is an isoquinoline alkaloid reported to have analgesic, anticancer, anti-inflammatory, and myocardial protective properties (Cicero and Baggioni, 2016). Sci.

Berberine attenuated the cytotoxicity induced by t-BHP via inhibiting oxidative stress and mitochondria dysfunction in PC-12 cells. Thousands of years ago, Indians and Chinese described the health-giving effects of this substance, derived from the turmeric plant (Gupta et al., 2014). Metab. Caloric restriction and its mimetics. Clinical studies with curcumin.

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. However, in vitro studies aimed at identifying cellular targets linked to the beneficial actions of phytonutrient-rich foods at concentrations ranging from nM to M challenge the translatability of data. 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). 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). AMP-Activated Protein Kinase and Sirtuin 1 Coregulation of Cortactin Contributes to Endothelial Function. RSV-induced MnSOD also reduces oxidative stress (Li et al., 2020a). (2013). Arch. Med. Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid beta-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice. Two clinical trials tested the anti-diabetic effect of BBR in patients with diabetes or diabetes and dyslipidemia (NCT00425009 and NCT00462046). A greater insight into the selectivity and specificity of natural SIRT activators may help understand the myriad beneficial effects described to date. The protective effect of RSV is associated with an increase in SIRT1 activity, which deacetylates FOXO1 and activates MnSOD downstream. 17 (1), 111. doi:10.1186/s12933-018-0754-4, Wan, D., Zhou, Y., Wang, K., Hou, Y., Hou, R., Ye, X. A list of completed studies using Que in different metabolic and inflammatory conditions is reported in Table 3. (2018).

J. Nutr. However, the mechanisms underlying these effects remain unclear. Molecules 19 (12), 2009120112.

Biochem. doi:10.1038/s41586-019-1411-0, Chang, H. C., Guarente, L. (2014). (2018). The main mechanisms of action common to polyphenol and non-polyphenol molecules that lead to antioxidant and anti-inflammatory effects via SIRT1 activation are reported in Figure 1. Due to its poor solubility, short half-life, and low bioavailability, its medical use is limited (Konrad and Nieman, 2015). Eur. Cur can downregulate expression of growth factor receptors, transcription factors, TNFs, and nitric oxide synthase, and increase AMPK levels. Biochim. Natural substances have beneficial effects on human health by regulating SIRT1 action in different cellular processes (www.pubchem.ncbi.nlm.nih.gov). The overproduction of reactive oxygen species (ROS), including free radicals, and reactive nitrogen species (RNS) can lead to damage of cellular components, such as lipids, proteins, and DNA. CI, MS, AN, and LA contributed to the redaction of the manuscript and gave final approval of the manuscript. doi:10.1007/978-0-387-46401-5_21, Hsu, C. P., Zhai, P., Yamamoto, T., Maejima, Y., Matsushima, S., Hariharan, N., et al. Mol. Pharm. Epigenetic modifications are associated with genome stability, gene transcription, and metabolic regulation. In inflammation, Que inhibits the enzymes COX and lipoxygenase (Lee and Min, 2013; Savikin et al., 2017). Fisetin was shown to increase SIRT1 expression and enhance SIRT1-mediated PPAR and FOXO1 deacetylation in 3T3L1 cells (Kim et al., 2015). (2004). J. Nutr. Biochem. doi:10.1002/jcb.28255, Theodotou, M., Fokianos, K., Mouzouridou, A., Konstantinou, C., Aristotelous, A., Prodromou, D., et al. The effect of resveratrol on hypertension: A clinical trial. RSV also has anti-inflammatory, anticancer, and anti-neurodegenerative effects (Piotrowska et al., 2012). J. Appl.

9:19:19. doi:10.3389/fphar.2018.00019, Svajger, U., Jeras, M. (2012). Specifically, BBR exerted an antioxidant effect by decreasing the generation of cardiac superoxide and gp91phox expression, and by increasing SOD levels (Yu et al., 2016). BioMed. Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving SIRT1 and PGC-1alpha.

doi:10.1016/j.cmet.2012.04.003, Priyadarsini, K. I. We will also discuss the potential therapeutic effects of these natural compounds in the prevention and treatment of human disorders, with particular emphasis on their metabolic impact. 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). Although RSV is beneficial in many contexts, its pleiotropic actions need to be better studied in order to understand which of its described activities are directly due to SIRT1 modulation and whether this effect is always direct. Biochem. NF-B deregulation can influence other mechanisms in which SIRT1 and AMPK are involved, such as glucose absorption in skeletal muscle. J. Endocrinol. The dietary flavonoid fisetin (3,3,4,7-tetra-hydroxyflavone) is a natural polyphenol present in plants and fruits such as apples, persimmons, grapes, onions, kiwi, kale, and strawberries, whose daily intake is estimated to be about 0.4mg (Khan et al., 2013). BioMed. Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application.

Via regulation of p53 deacetylation and modulation of autophagy, SIRT1 is implicated in cellular response to caloric restriction and lifespan extension. Int. B. Berberine and Its Role in Chronic Disease. Sirtuins at the crossroads of stemness, aging, and cancer. Biophys. Adv. 3 (4), 437441. Interv. Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2/HO-1 and JAK/STAT pathways.

Cell Longev. Biofactors 46 (1), 168179. Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy. Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats. 25 (1), 118. Various supplements use a mixture of macroalgae, others stick to one and some products combine fucoidan with vitamins or other ingredients; as with all supplements, customers should examine provenance, purity and efficacy before deciding on a regimen, and luckily there is a wealth of academic evidence on the effects of fucoidan out there for the interested reader. doi:10.1016/j.biopha.2018.11.064, PubMed Abstract | CrossRef Full Text | Google Scholar, Araki, T., Sasaki, Y., Milbrandt, J. In recent years, the scientific community has focused on the role of apoptosis in cardiovascular disease, showing that oxidative stress, myocardial ischemia, hypoxia, and ischemia/reperfusion injury may induce myocardial apoptosis (Donniacuo et al., 2019). Cur-induced SIRT1 upregulation has beneficial effects against a range of diseases including cardiac fibrosis, diabetes, and ischemia/reperfusion injury (Zendedel et al., 2018 #7; Yang et al., 2013 #5). Nevertheless, the mechanisms of action are not yet well defined. Resveratrol improves left ventricular remodeling in chronic kidney disease via Sirt1-mediated regulation of FoxO1 activity and MnSOD expression. 49 (5), 18701884. A list of completed and terminated clinical trials investigating the effects of Cur in metabolic and inflammatory diseases is reported in Table 5. 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. Front. doi:10.18632/aging.103059, Huang, S. X., Qiu, G., Cheng, F. R., Pei, Z., Yang, Z., Deng, X. H., et al. Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1. doi:10.1016/j.cmet.2013.02.001, Brasnyo, P., Molnar, G. A., Mohas, M., Marko, L., Laczy, B., Cseh, J., et al. B., Zhang, S. J.. (2020). 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. Brain Res. (2016). J. Chin. (2015). Numerous studies have provided evidence of the protective effects of natural polyphenolic substances such as resveratrol, quercetin, curcumin, and fisetin, and of natural non-polyphenolic substances such as berberine (McCubrey et al., 2017). Physiol. Trends Endocrinol.

Redox Signal 18 (14), 18181892.

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).

In mammalians, RSV administration can improve SIRT1-dependent cellular processes such as axonal protection (Araki et al., 2004), fat mobilization (Chaplin et al., 2018), and inhibition of NF-B-dependent transcription (Yeung et al., 2019); these effects are abolished in SIRT1 knockdown models. Under normal conditions, the cystine-rich zinc Keap1 metalloprotein binds Nrf2 inside the cytoplasm, promoting ubiquitination and consequent proteasomal degradation and preventing Nrf2 nuclear translocation (Serafini et al., 2019). In addition, a phase 2 clinical study (NCT03216811) assessed the efficacy of a nutraceutical compound (3 mg containing fermented red rice) in terms of cholesterol, and endothelial and inflammatory parameters in subjects with hypercholesterolemia and low-to-moderate cardiovascular risk. doi:10.1038/sj.emboj.7600244, Yeung, A. W. K., Tzvetkov, N. T., El-Tawil, O. S., Bungau, S. G., Abdel-Daim, M. M., Atanasov, A. G. (2019). (2013). The lipid-lowering activity mediated by co-treatment with BBR and RSV was investigated in mice exposed to a high fat diet (Zhu et al., 2018). A list of clinical studies investigating the beneficial effects of BBR in inflammatory and metabolic diseases is reported in Table 4.

Sitemap 48